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Developing Students’ Critical Thinking through Online Discussions: A Literature Review

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2019, Malaysian Online Journal of Educational Technology

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Literature Review Tips for the Introduction and Discussion Sections

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A literature review is a summary of studies related to a particular area of research. It identifies and summarizes all the relevant research conducted on a particular topic. It is important that your literature review is focused . Therefore, you should choose a limited number of studies that are central to your topic rather than trying to collect a wide range of studies that might not be closely connected.

Literature reviews help you accomplish the following:

  • Evaluate past research  Collecting relevant resources will help you see what research has already been done. This will also help avoid duplication.
  • Identify experts It is important to identify credible researchers who have knowledge in a given field, in order to seek their help if you get stuck with certain aspects of your research.
  • Identify key questions  Your ultimate aim is to bring something new to the conversation. Collecting resources will help you determine the important questions that need to be addressed.
  • Determine methodologies used in past studies Knowing how others have approached a particular topic will give you the opportunity to identify problems and find new ways to research and study a topic. If the reported methodology was successful, you can use it and save time that you would otherwise be spending on optimization.

Presenting Literature Review in the Introduction and Discussion Sections

There are many benefits to presenting literature reviews in the introduction and discussion sections of your manuscripts . However, there are differences in how you can present literature reviews in each section.

What Should be Included in the Literature Review of the Introduction Section?

The literature reviewed in the introduction should:

  • Introduce the topic
  • Establish the significance of the study
  • Provide an overview of the relevant literature
  • Establish a context for the study using the literature
  • Identify knowledge gaps
  • Illustrate how the study will advance knowledge on the topic

As you can see, literature review plays a significant role in the introduction section. However, there are some things that you should avoid doing in this section. These include:

  • Elaborating on the studies mentioned in the literature review
  • Using studies from the literature review to aggressively support your research
  • Directly quoting studies from the literature review

It is important to know how to integrate the literature review into the introduction in an effective way. Although you can mention other studies, they should not be the focus. Instead, focus on using the literature review to aid in setting a foundation for the manuscript.

What Goes in the Literature Review of the Discussion Section?

Literature reviews play an important role in the discussion section of a manuscript . In this section, your findings should be the focus, rather than those of other researchers. Therefore, you should only use the studies mentioned in the literature review as support and evidence for your study.

There are three ways in which you can use literature reviews in the discussion section:

  • To Provide Context for Your Study Using studies from the literature review helps to set the foundation for how you will reveal your findings and develop your ideas.
  • Compare your Findings to Other Studies You can use previous literature as a backdrop to compare your new findings. This helps describe and also advance your ideas.
  • State the Contribution of Your Study In addition to developing your ideas, you can use literature reviews to explain how your study contributes to the field of study.

However, there are three common mistakes that researchers make when including literature reviews in the discussion section. First, they mention all sorts of studies, some of which are not even relevant to the topic under investigation. Second, instead of citing the original article, they cite a related article that mentions the original article. Lastly, some authors cite previous work solely based on the abstract, without even going through the entire paper.

We hope this article helps you effectively present your literature review in both the introduction as well as the discussion section of your manuscript. You can also mention any other tips that will add to this article in the comments section below.

References:

[1]  http://www.math.montana.edu/jobo/phdprep/documents/phd6.pdf 

[2]  https://libguides.unf.edu/c.php?g=177129&p=1163732

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  • How to Write a Discussion Section | Tips & Examples

How to Write a Discussion Section | Tips & Examples

Published on August 21, 2022 by Shona McCombes . Revised on July 18, 2023.

Discussion section flow chart

The discussion section is where you delve into the meaning, importance, and relevance of your results .

It should focus on explaining and evaluating what you found, showing how it relates to your literature review and paper or dissertation topic , and making an argument in support of your overall conclusion. It should not be a second results section.

There are different ways to write this section, but you can focus your writing around these key elements:

  • Summary : A brief recap of your key results
  • Interpretations: What do your results mean?
  • Implications: Why do your results matter?
  • Limitations: What can’t your results tell us?
  • Recommendations: Avenues for further studies or analyses

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Table of contents

What not to include in your discussion section, step 1: summarize your key findings, step 2: give your interpretations, step 3: discuss the implications, step 4: acknowledge the limitations, step 5: share your recommendations, discussion section example, other interesting articles, frequently asked questions about discussion sections.

There are a few common mistakes to avoid when writing the discussion section of your paper.

  • Don’t introduce new results: You should only discuss the data that you have already reported in your results section .
  • Don’t make inflated claims: Avoid overinterpretation and speculation that isn’t directly supported by your data.
  • Don’t undermine your research: The discussion of limitations should aim to strengthen your credibility, not emphasize weaknesses or failures.

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literature review on online discussion

Start this section by reiterating your research problem and concisely summarizing your major findings. To speed up the process you can use a summarizer to quickly get an overview of all important findings. Don’t just repeat all the data you have already reported—aim for a clear statement of the overall result that directly answers your main research question . This should be no more than one paragraph.

Many students struggle with the differences between a discussion section and a results section . The crux of the matter is that your results sections should present your results, and your discussion section should subjectively evaluate them. Try not to blend elements of these two sections, in order to keep your paper sharp.

  • The results indicate that…
  • The study demonstrates a correlation between…
  • This analysis supports the theory that…
  • The data suggest that…

The meaning of your results may seem obvious to you, but it’s important to spell out their significance for your reader, showing exactly how they answer your research question.

The form of your interpretations will depend on the type of research, but some typical approaches to interpreting the data include:

  • Identifying correlations , patterns, and relationships among the data
  • Discussing whether the results met your expectations or supported your hypotheses
  • Contextualizing your findings within previous research and theory
  • Explaining unexpected results and evaluating their significance
  • Considering possible alternative explanations and making an argument for your position

You can organize your discussion around key themes, hypotheses, or research questions, following the same structure as your results section. Alternatively, you can also begin by highlighting the most significant or unexpected results.

  • In line with the hypothesis…
  • Contrary to the hypothesized association…
  • The results contradict the claims of Smith (2022) that…
  • The results might suggest that x . However, based on the findings of similar studies, a more plausible explanation is y .

As well as giving your own interpretations, make sure to relate your results back to the scholarly work that you surveyed in the literature review . The discussion should show how your findings fit with existing knowledge, what new insights they contribute, and what consequences they have for theory or practice.

Ask yourself these questions:

  • Do your results support or challenge existing theories? If they support existing theories, what new information do they contribute? If they challenge existing theories, why do you think that is?
  • Are there any practical implications?

Your overall aim is to show the reader exactly what your research has contributed, and why they should care.

  • These results build on existing evidence of…
  • The results do not fit with the theory that…
  • The experiment provides a new insight into the relationship between…
  • These results should be taken into account when considering how to…
  • The data contribute a clearer understanding of…
  • While previous research has focused on  x , these results demonstrate that y .

Even the best research has its limitations. Acknowledging these is important to demonstrate your credibility. Limitations aren’t about listing your errors, but about providing an accurate picture of what can and cannot be concluded from your study.

Limitations might be due to your overall research design, specific methodological choices , or unanticipated obstacles that emerged during your research process.

Here are a few common possibilities:

  • If your sample size was small or limited to a specific group of people, explain how generalizability is limited.
  • If you encountered problems when gathering or analyzing data, explain how these influenced the results.
  • If there are potential confounding variables that you were unable to control, acknowledge the effect these may have had.

After noting the limitations, you can reiterate why the results are nonetheless valid for the purpose of answering your research question.

  • The generalizability of the results is limited by…
  • The reliability of these data is impacted by…
  • Due to the lack of data on x , the results cannot confirm…
  • The methodological choices were constrained by…
  • It is beyond the scope of this study to…

Based on the discussion of your results, you can make recommendations for practical implementation or further research. Sometimes, the recommendations are saved for the conclusion .

Suggestions for further research can lead directly from the limitations. Don’t just state that more studies should be done—give concrete ideas for how future work can build on areas that your own research was unable to address.

  • Further research is needed to establish…
  • Future studies should take into account…
  • Avenues for future research include…

Discussion section example

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In the discussion , you explore the meaning and relevance of your research results , explaining how they fit with existing research and theory. Discuss:

  • Your  interpretations : what do the results tell us?
  • The  implications : why do the results matter?
  • The  limitation s : what can’t the results tell us?

The results chapter or section simply and objectively reports what you found, without speculating on why you found these results. The discussion interprets the meaning of the results, puts them in context, and explains why they matter.

In qualitative research , results and discussion are sometimes combined. But in quantitative research , it’s considered important to separate the objective results from your interpretation of them.

In a thesis or dissertation, the discussion is an in-depth exploration of the results, going into detail about the meaning of your findings and citing relevant sources to put them in context.

The conclusion is more shorter and more general: it concisely answers your main research question and makes recommendations based on your overall findings.

Cite this Scribbr article

If you want to cite this source, you can copy and paste the citation or click the “Cite this Scribbr article” button to automatically add the citation to our free Citation Generator.

McCombes, S. (2023, July 18). How to Write a Discussion Section | Tips & Examples. Scribbr. Retrieved March 8, 2024, from https://www.scribbr.com/dissertation/discussion/

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  • 04 December 2020
  • Correction 09 December 2020

How to write a superb literature review

Andy Tay is a freelance writer based in Singapore.

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Literature reviews are important resources for scientists. They provide historical context for a field while offering opinions on its future trajectory. Creating them can provide inspiration for one’s own research, as well as some practice in writing. But few scientists are trained in how to write a review — or in what constitutes an excellent one. Even picking the appropriate software to use can be an involved decision (see ‘Tools and techniques’). So Nature asked editors and working scientists with well-cited reviews for their tips.

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Hsing, I.-M., Xu, Y. & Zhao, W. Electroanalysis 19 , 755–768 (2007).

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Writing a Literature Review

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A literature review is a document or section of a document that collects key sources on a topic and discusses those sources in conversation with each other (also called synthesis ). The lit review is an important genre in many disciplines, not just literature (i.e., the study of works of literature such as novels and plays). When we say “literature review” or refer to “the literature,” we are talking about the research ( scholarship ) in a given field. You will often see the terms “the research,” “the scholarship,” and “the literature” used mostly interchangeably.

Where, when, and why would I write a lit review?

There are a number of different situations where you might write a literature review, each with slightly different expectations; different disciplines, too, have field-specific expectations for what a literature review is and does. For instance, in the humanities, authors might include more overt argumentation and interpretation of source material in their literature reviews, whereas in the sciences, authors are more likely to report study designs and results in their literature reviews; these differences reflect these disciplines’ purposes and conventions in scholarship. You should always look at examples from your own discipline and talk to professors or mentors in your field to be sure you understand your discipline’s conventions, for literature reviews as well as for any other genre.

A literature review can be a part of a research paper or scholarly article, usually falling after the introduction and before the research methods sections. In these cases, the lit review just needs to cover scholarship that is important to the issue you are writing about; sometimes it will also cover key sources that informed your research methodology.

Lit reviews can also be standalone pieces, either as assignments in a class or as publications. In a class, a lit review may be assigned to help students familiarize themselves with a topic and with scholarship in their field, get an idea of the other researchers working on the topic they’re interested in, find gaps in existing research in order to propose new projects, and/or develop a theoretical framework and methodology for later research. As a publication, a lit review usually is meant to help make other scholars’ lives easier by collecting and summarizing, synthesizing, and analyzing existing research on a topic. This can be especially helpful for students or scholars getting into a new research area, or for directing an entire community of scholars toward questions that have not yet been answered.

What are the parts of a lit review?

Most lit reviews use a basic introduction-body-conclusion structure; if your lit review is part of a larger paper, the introduction and conclusion pieces may be just a few sentences while you focus most of your attention on the body. If your lit review is a standalone piece, the introduction and conclusion take up more space and give you a place to discuss your goals, research methods, and conclusions separately from where you discuss the literature itself.

Introduction:

  • An introductory paragraph that explains what your working topic and thesis is
  • A forecast of key topics or texts that will appear in the review
  • Potentially, a description of how you found sources and how you analyzed them for inclusion and discussion in the review (more often found in published, standalone literature reviews than in lit review sections in an article or research paper)
  • Summarize and synthesize: Give an overview of the main points of each source and combine them into a coherent whole
  • Analyze and interpret: Don’t just paraphrase other researchers – add your own interpretations where possible, discussing the significance of findings in relation to the literature as a whole
  • Critically Evaluate: Mention the strengths and weaknesses of your sources
  • Write in well-structured paragraphs: Use transition words and topic sentence to draw connections, comparisons, and contrasts.

Conclusion:

  • Summarize the key findings you have taken from the literature and emphasize their significance
  • Connect it back to your primary research question

How should I organize my lit review?

Lit reviews can take many different organizational patterns depending on what you are trying to accomplish with the review. Here are some examples:

  • Chronological : The simplest approach is to trace the development of the topic over time, which helps familiarize the audience with the topic (for instance if you are introducing something that is not commonly known in your field). If you choose this strategy, be careful to avoid simply listing and summarizing sources in order. Try to analyze the patterns, turning points, and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred (as mentioned previously, this may not be appropriate in your discipline — check with a teacher or mentor if you’re unsure).
  • Thematic : If you have found some recurring central themes that you will continue working with throughout your piece, you can organize your literature review into subsections that address different aspects of the topic. For example, if you are reviewing literature about women and religion, key themes can include the role of women in churches and the religious attitude towards women.
  • Qualitative versus quantitative research
  • Empirical versus theoretical scholarship
  • Divide the research by sociological, historical, or cultural sources
  • Theoretical : In many humanities articles, the literature review is the foundation for the theoretical framework. You can use it to discuss various theories, models, and definitions of key concepts. You can argue for the relevance of a specific theoretical approach or combine various theorical concepts to create a framework for your research.

What are some strategies or tips I can use while writing my lit review?

Any lit review is only as good as the research it discusses; make sure your sources are well-chosen and your research is thorough. Don’t be afraid to do more research if you discover a new thread as you’re writing. More info on the research process is available in our "Conducting Research" resources .

As you’re doing your research, create an annotated bibliography ( see our page on the this type of document ). Much of the information used in an annotated bibliography can be used also in a literature review, so you’ll be not only partially drafting your lit review as you research, but also developing your sense of the larger conversation going on among scholars, professionals, and any other stakeholders in your topic.

Usually you will need to synthesize research rather than just summarizing it. This means drawing connections between sources to create a picture of the scholarly conversation on a topic over time. Many student writers struggle to synthesize because they feel they don’t have anything to add to the scholars they are citing; here are some strategies to help you:

  • It often helps to remember that the point of these kinds of syntheses is to show your readers how you understand your research, to help them read the rest of your paper.
  • Writing teachers often say synthesis is like hosting a dinner party: imagine all your sources are together in a room, discussing your topic. What are they saying to each other?
  • Look at the in-text citations in each paragraph. Are you citing just one source for each paragraph? This usually indicates summary only. When you have multiple sources cited in a paragraph, you are more likely to be synthesizing them (not always, but often
  • Read more about synthesis here.

The most interesting literature reviews are often written as arguments (again, as mentioned at the beginning of the page, this is discipline-specific and doesn’t work for all situations). Often, the literature review is where you can establish your research as filling a particular gap or as relevant in a particular way. You have some chance to do this in your introduction in an article, but the literature review section gives a more extended opportunity to establish the conversation in the way you would like your readers to see it. You can choose the intellectual lineage you would like to be part of and whose definitions matter most to your thinking (mostly humanities-specific, but this goes for sciences as well). In addressing these points, you argue for your place in the conversation, which tends to make the lit review more compelling than a simple reporting of other sources.

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Guy Paré and Spyros Kitsiou .

9.1. Introduction

Literature reviews play a critical role in scholarship because science remains, first and foremost, a cumulative endeavour ( vom Brocke et al., 2009 ). As in any academic discipline, rigorous knowledge syntheses are becoming indispensable in keeping up with an exponentially growing eHealth literature, assisting practitioners, academics, and graduate students in finding, evaluating, and synthesizing the contents of many empirical and conceptual papers. Among other methods, literature reviews are essential for: (a) identifying what has been written on a subject or topic; (b) determining the extent to which a specific research area reveals any interpretable trends or patterns; (c) aggregating empirical findings related to a narrow research question to support evidence-based practice; (d) generating new frameworks and theories; and (e) identifying topics or questions requiring more investigation ( Paré, Trudel, Jaana, & Kitsiou, 2015 ).

Literature reviews can take two major forms. The most prevalent one is the “literature review” or “background” section within a journal paper or a chapter in a graduate thesis. This section synthesizes the extant literature and usually identifies the gaps in knowledge that the empirical study addresses ( Sylvester, Tate, & Johnstone, 2013 ). It may also provide a theoretical foundation for the proposed study, substantiate the presence of the research problem, justify the research as one that contributes something new to the cumulated knowledge, or validate the methods and approaches for the proposed study ( Hart, 1998 ; Levy & Ellis, 2006 ).

The second form of literature review, which is the focus of this chapter, constitutes an original and valuable work of research in and of itself ( Paré et al., 2015 ). Rather than providing a base for a researcher’s own work, it creates a solid starting point for all members of the community interested in a particular area or topic ( Mulrow, 1987 ). The so-called “review article” is a journal-length paper which has an overarching purpose to synthesize the literature in a field, without collecting or analyzing any primary data ( Green, Johnson, & Adams, 2006 ).

When appropriately conducted, review articles represent powerful information sources for practitioners looking for state-of-the art evidence to guide their decision-making and work practices ( Paré et al., 2015 ). Further, high-quality reviews become frequently cited pieces of work which researchers seek out as a first clear outline of the literature when undertaking empirical studies ( Cooper, 1988 ; Rowe, 2014 ). Scholars who track and gauge the impact of articles have found that review papers are cited and downloaded more often than any other type of published article ( Cronin, Ryan, & Coughlan, 2008 ; Montori, Wilczynski, Morgan, Haynes, & Hedges, 2003 ; Patsopoulos, Analatos, & Ioannidis, 2005 ). The reason for their popularity may be the fact that reading the review enables one to have an overview, if not a detailed knowledge of the area in question, as well as references to the most useful primary sources ( Cronin et al., 2008 ). Although they are not easy to conduct, the commitment to complete a review article provides a tremendous service to one’s academic community ( Paré et al., 2015 ; Petticrew & Roberts, 2006 ). Most, if not all, peer-reviewed journals in the fields of medical informatics publish review articles of some type.

The main objectives of this chapter are fourfold: (a) to provide an overview of the major steps and activities involved in conducting a stand-alone literature review; (b) to describe and contrast the different types of review articles that can contribute to the eHealth knowledge base; (c) to illustrate each review type with one or two examples from the eHealth literature; and (d) to provide a series of recommendations for prospective authors of review articles in this domain.

9.2. Overview of the Literature Review Process and Steps

As explained in Templier and Paré (2015) , there are six generic steps involved in conducting a review article:

  • formulating the research question(s) and objective(s),
  • searching the extant literature,
  • screening for inclusion,
  • assessing the quality of primary studies,
  • extracting data, and
  • analyzing data.

Although these steps are presented here in sequential order, one must keep in mind that the review process can be iterative and that many activities can be initiated during the planning stage and later refined during subsequent phases ( Finfgeld-Connett & Johnson, 2013 ; Kitchenham & Charters, 2007 ).

Formulating the research question(s) and objective(s): As a first step, members of the review team must appropriately justify the need for the review itself ( Petticrew & Roberts, 2006 ), identify the review’s main objective(s) ( Okoli & Schabram, 2010 ), and define the concepts or variables at the heart of their synthesis ( Cooper & Hedges, 2009 ; Webster & Watson, 2002 ). Importantly, they also need to articulate the research question(s) they propose to investigate ( Kitchenham & Charters, 2007 ). In this regard, we concur with Jesson, Matheson, and Lacey (2011) that clearly articulated research questions are key ingredients that guide the entire review methodology; they underscore the type of information that is needed, inform the search for and selection of relevant literature, and guide or orient the subsequent analysis. Searching the extant literature: The next step consists of searching the literature and making decisions about the suitability of material to be considered in the review ( Cooper, 1988 ). There exist three main coverage strategies. First, exhaustive coverage means an effort is made to be as comprehensive as possible in order to ensure that all relevant studies, published and unpublished, are included in the review and, thus, conclusions are based on this all-inclusive knowledge base. The second type of coverage consists of presenting materials that are representative of most other works in a given field or area. Often authors who adopt this strategy will search for relevant articles in a small number of top-tier journals in a field ( Paré et al., 2015 ). In the third strategy, the review team concentrates on prior works that have been central or pivotal to a particular topic. This may include empirical studies or conceptual papers that initiated a line of investigation, changed how problems or questions were framed, introduced new methods or concepts, or engendered important debate ( Cooper, 1988 ). Screening for inclusion: The following step consists of evaluating the applicability of the material identified in the preceding step ( Levy & Ellis, 2006 ; vom Brocke et al., 2009 ). Once a group of potential studies has been identified, members of the review team must screen them to determine their relevance ( Petticrew & Roberts, 2006 ). A set of predetermined rules provides a basis for including or excluding certain studies. This exercise requires a significant investment on the part of researchers, who must ensure enhanced objectivity and avoid biases or mistakes. As discussed later in this chapter, for certain types of reviews there must be at least two independent reviewers involved in the screening process and a procedure to resolve disagreements must also be in place ( Liberati et al., 2009 ; Shea et al., 2009 ). Assessing the quality of primary studies: In addition to screening material for inclusion, members of the review team may need to assess the scientific quality of the selected studies, that is, appraise the rigour of the research design and methods. Such formal assessment, which is usually conducted independently by at least two coders, helps members of the review team refine which studies to include in the final sample, determine whether or not the differences in quality may affect their conclusions, or guide how they analyze the data and interpret the findings ( Petticrew & Roberts, 2006 ). Ascribing quality scores to each primary study or considering through domain-based evaluations which study components have or have not been designed and executed appropriately makes it possible to reflect on the extent to which the selected study addresses possible biases and maximizes validity ( Shea et al., 2009 ). Extracting data: The following step involves gathering or extracting applicable information from each primary study included in the sample and deciding what is relevant to the problem of interest ( Cooper & Hedges, 2009 ). Indeed, the type of data that should be recorded mainly depends on the initial research questions ( Okoli & Schabram, 2010 ). However, important information may also be gathered about how, when, where and by whom the primary study was conducted, the research design and methods, or qualitative/quantitative results ( Cooper & Hedges, 2009 ). Analyzing and synthesizing data : As a final step, members of the review team must collate, summarize, aggregate, organize, and compare the evidence extracted from the included studies. The extracted data must be presented in a meaningful way that suggests a new contribution to the extant literature ( Jesson et al., 2011 ). Webster and Watson (2002) warn researchers that literature reviews should be much more than lists of papers and should provide a coherent lens to make sense of extant knowledge on a given topic. There exist several methods and techniques for synthesizing quantitative (e.g., frequency analysis, meta-analysis) and qualitative (e.g., grounded theory, narrative analysis, meta-ethnography) evidence ( Dixon-Woods, Agarwal, Jones, Young, & Sutton, 2005 ; Thomas & Harden, 2008 ).

9.3. Types of Review Articles and Brief Illustrations

EHealth researchers have at their disposal a number of approaches and methods for making sense out of existing literature, all with the purpose of casting current research findings into historical contexts or explaining contradictions that might exist among a set of primary research studies conducted on a particular topic. Our classification scheme is largely inspired from Paré and colleagues’ (2015) typology. Below we present and illustrate those review types that we feel are central to the growth and development of the eHealth domain.

9.3.1. Narrative Reviews

The narrative review is the “traditional” way of reviewing the extant literature and is skewed towards a qualitative interpretation of prior knowledge ( Sylvester et al., 2013 ). Put simply, a narrative review attempts to summarize or synthesize what has been written on a particular topic but does not seek generalization or cumulative knowledge from what is reviewed ( Davies, 2000 ; Green et al., 2006 ). Instead, the review team often undertakes the task of accumulating and synthesizing the literature to demonstrate the value of a particular point of view ( Baumeister & Leary, 1997 ). As such, reviewers may selectively ignore or limit the attention paid to certain studies in order to make a point. In this rather unsystematic approach, the selection of information from primary articles is subjective, lacks explicit criteria for inclusion and can lead to biased interpretations or inferences ( Green et al., 2006 ). There are several narrative reviews in the particular eHealth domain, as in all fields, which follow such an unstructured approach ( Silva et al., 2015 ; Paul et al., 2015 ).

Despite these criticisms, this type of review can be very useful in gathering together a volume of literature in a specific subject area and synthesizing it. As mentioned above, its primary purpose is to provide the reader with a comprehensive background for understanding current knowledge and highlighting the significance of new research ( Cronin et al., 2008 ). Faculty like to use narrative reviews in the classroom because they are often more up to date than textbooks, provide a single source for students to reference, and expose students to peer-reviewed literature ( Green et al., 2006 ). For researchers, narrative reviews can inspire research ideas by identifying gaps or inconsistencies in a body of knowledge, thus helping researchers to determine research questions or formulate hypotheses. Importantly, narrative reviews can also be used as educational articles to bring practitioners up to date with certain topics of issues ( Green et al., 2006 ).

Recently, there have been several efforts to introduce more rigour in narrative reviews that will elucidate common pitfalls and bring changes into their publication standards. Information systems researchers, among others, have contributed to advancing knowledge on how to structure a “traditional” review. For instance, Levy and Ellis (2006) proposed a generic framework for conducting such reviews. Their model follows the systematic data processing approach comprised of three steps, namely: (a) literature search and screening; (b) data extraction and analysis; and (c) writing the literature review. They provide detailed and very helpful instructions on how to conduct each step of the review process. As another methodological contribution, vom Brocke et al. (2009) offered a series of guidelines for conducting literature reviews, with a particular focus on how to search and extract the relevant body of knowledge. Last, Bandara, Miskon, and Fielt (2011) proposed a structured, predefined and tool-supported method to identify primary studies within a feasible scope, extract relevant content from identified articles, synthesize and analyze the findings, and effectively write and present the results of the literature review. We highly recommend that prospective authors of narrative reviews consult these useful sources before embarking on their work.

Darlow and Wen (2015) provide a good example of a highly structured narrative review in the eHealth field. These authors synthesized published articles that describe the development process of mobile health ( m-health ) interventions for patients’ cancer care self-management. As in most narrative reviews, the scope of the research questions being investigated is broad: (a) how development of these systems are carried out; (b) which methods are used to investigate these systems; and (c) what conclusions can be drawn as a result of the development of these systems. To provide clear answers to these questions, a literature search was conducted on six electronic databases and Google Scholar . The search was performed using several terms and free text words, combining them in an appropriate manner. Four inclusion and three exclusion criteria were utilized during the screening process. Both authors independently reviewed each of the identified articles to determine eligibility and extract study information. A flow diagram shows the number of studies identified, screened, and included or excluded at each stage of study selection. In terms of contributions, this review provides a series of practical recommendations for m-health intervention development.

9.3.2. Descriptive or Mapping Reviews

The primary goal of a descriptive review is to determine the extent to which a body of knowledge in a particular research topic reveals any interpretable pattern or trend with respect to pre-existing propositions, theories, methodologies or findings ( King & He, 2005 ; Paré et al., 2015 ). In contrast with narrative reviews, descriptive reviews follow a systematic and transparent procedure, including searching, screening and classifying studies ( Petersen, Vakkalanka, & Kuzniarz, 2015 ). Indeed, structured search methods are used to form a representative sample of a larger group of published works ( Paré et al., 2015 ). Further, authors of descriptive reviews extract from each study certain characteristics of interest, such as publication year, research methods, data collection techniques, and direction or strength of research outcomes (e.g., positive, negative, or non-significant) in the form of frequency analysis to produce quantitative results ( Sylvester et al., 2013 ). In essence, each study included in a descriptive review is treated as the unit of analysis and the published literature as a whole provides a database from which the authors attempt to identify any interpretable trends or draw overall conclusions about the merits of existing conceptualizations, propositions, methods or findings ( Paré et al., 2015 ). In doing so, a descriptive review may claim that its findings represent the state of the art in a particular domain ( King & He, 2005 ).

In the fields of health sciences and medical informatics, reviews that focus on examining the range, nature and evolution of a topic area are described by Anderson, Allen, Peckham, and Goodwin (2008) as mapping reviews . Like descriptive reviews, the research questions are generic and usually relate to publication patterns and trends. There is no preconceived plan to systematically review all of the literature although this can be done. Instead, researchers often present studies that are representative of most works published in a particular area and they consider a specific time frame to be mapped.

An example of this approach in the eHealth domain is offered by DeShazo, Lavallie, and Wolf (2009). The purpose of this descriptive or mapping review was to characterize publication trends in the medical informatics literature over a 20-year period (1987 to 2006). To achieve this ambitious objective, the authors performed a bibliometric analysis of medical informatics citations indexed in medline using publication trends, journal frequencies, impact factors, Medical Subject Headings (MeSH) term frequencies, and characteristics of citations. Findings revealed that there were over 77,000 medical informatics articles published during the covered period in numerous journals and that the average annual growth rate was 12%. The MeSH term analysis also suggested a strong interdisciplinary trend. Finally, average impact scores increased over time with two notable growth periods. Overall, patterns in research outputs that seem to characterize the historic trends and current components of the field of medical informatics suggest it may be a maturing discipline (DeShazo et al., 2009).

9.3.3. Scoping Reviews

Scoping reviews attempt to provide an initial indication of the potential size and nature of the extant literature on an emergent topic (Arksey & O’Malley, 2005; Daudt, van Mossel, & Scott, 2013 ; Levac, Colquhoun, & O’Brien, 2010). A scoping review may be conducted to examine the extent, range and nature of research activities in a particular area, determine the value of undertaking a full systematic review (discussed next), or identify research gaps in the extant literature ( Paré et al., 2015 ). In line with their main objective, scoping reviews usually conclude with the presentation of a detailed research agenda for future works along with potential implications for both practice and research.

Unlike narrative and descriptive reviews, the whole point of scoping the field is to be as comprehensive as possible, including grey literature (Arksey & O’Malley, 2005). Inclusion and exclusion criteria must be established to help researchers eliminate studies that are not aligned with the research questions. It is also recommended that at least two independent coders review abstracts yielded from the search strategy and then the full articles for study selection ( Daudt et al., 2013 ). The synthesized evidence from content or thematic analysis is relatively easy to present in tabular form (Arksey & O’Malley, 2005; Thomas & Harden, 2008 ).

One of the most highly cited scoping reviews in the eHealth domain was published by Archer, Fevrier-Thomas, Lokker, McKibbon, and Straus (2011) . These authors reviewed the existing literature on personal health record ( phr ) systems including design, functionality, implementation, applications, outcomes, and benefits. Seven databases were searched from 1985 to March 2010. Several search terms relating to phr s were used during this process. Two authors independently screened titles and abstracts to determine inclusion status. A second screen of full-text articles, again by two independent members of the research team, ensured that the studies described phr s. All in all, 130 articles met the criteria and their data were extracted manually into a database. The authors concluded that although there is a large amount of survey, observational, cohort/panel, and anecdotal evidence of phr benefits and satisfaction for patients, more research is needed to evaluate the results of phr implementations. Their in-depth analysis of the literature signalled that there is little solid evidence from randomized controlled trials or other studies through the use of phr s. Hence, they suggested that more research is needed that addresses the current lack of understanding of optimal functionality and usability of these systems, and how they can play a beneficial role in supporting patient self-management ( Archer et al., 2011 ).

9.3.4. Forms of Aggregative Reviews

Healthcare providers, practitioners, and policy-makers are nowadays overwhelmed with large volumes of information, including research-based evidence from numerous clinical trials and evaluation studies, assessing the effectiveness of health information technologies and interventions ( Ammenwerth & de Keizer, 2004 ; Deshazo et al., 2009 ). It is unrealistic to expect that all these disparate actors will have the time, skills, and necessary resources to identify the available evidence in the area of their expertise and consider it when making decisions. Systematic reviews that involve the rigorous application of scientific strategies aimed at limiting subjectivity and bias (i.e., systematic and random errors) can respond to this challenge.

Systematic reviews attempt to aggregate, appraise, and synthesize in a single source all empirical evidence that meet a set of previously specified eligibility criteria in order to answer a clearly formulated and often narrow research question on a particular topic of interest to support evidence-based practice ( Liberati et al., 2009 ). They adhere closely to explicit scientific principles ( Liberati et al., 2009 ) and rigorous methodological guidelines (Higgins & Green, 2008) aimed at reducing random and systematic errors that can lead to deviations from the truth in results or inferences. The use of explicit methods allows systematic reviews to aggregate a large body of research evidence, assess whether effects or relationships are in the same direction and of the same general magnitude, explain possible inconsistencies between study results, and determine the strength of the overall evidence for every outcome of interest based on the quality of included studies and the general consistency among them ( Cook, Mulrow, & Haynes, 1997 ). The main procedures of a systematic review involve:

  • Formulating a review question and developing a search strategy based on explicit inclusion criteria for the identification of eligible studies (usually described in the context of a detailed review protocol).
  • Searching for eligible studies using multiple databases and information sources, including grey literature sources, without any language restrictions.
  • Selecting studies, extracting data, and assessing risk of bias in a duplicate manner using two independent reviewers to avoid random or systematic errors in the process.
  • Analyzing data using quantitative or qualitative methods.
  • Presenting results in summary of findings tables.
  • Interpreting results and drawing conclusions.

Many systematic reviews, but not all, use statistical methods to combine the results of independent studies into a single quantitative estimate or summary effect size. Known as meta-analyses , these reviews use specific data extraction and statistical techniques (e.g., network, frequentist, or Bayesian meta-analyses) to calculate from each study by outcome of interest an effect size along with a confidence interval that reflects the degree of uncertainty behind the point estimate of effect ( Borenstein, Hedges, Higgins, & Rothstein, 2009 ; Deeks, Higgins, & Altman, 2008 ). Subsequently, they use fixed or random-effects analysis models to combine the results of the included studies, assess statistical heterogeneity, and calculate a weighted average of the effect estimates from the different studies, taking into account their sample sizes. The summary effect size is a value that reflects the average magnitude of the intervention effect for a particular outcome of interest or, more generally, the strength of a relationship between two variables across all studies included in the systematic review. By statistically combining data from multiple studies, meta-analyses can create more precise and reliable estimates of intervention effects than those derived from individual studies alone, when these are examined independently as discrete sources of information.

The review by Gurol-Urganci, de Jongh, Vodopivec-Jamsek, Atun, and Car (2013) on the effects of mobile phone messaging reminders for attendance at healthcare appointments is an illustrative example of a high-quality systematic review with meta-analysis. Missed appointments are a major cause of inefficiency in healthcare delivery with substantial monetary costs to health systems. These authors sought to assess whether mobile phone-based appointment reminders delivered through Short Message Service ( sms ) or Multimedia Messaging Service ( mms ) are effective in improving rates of patient attendance and reducing overall costs. To this end, they conducted a comprehensive search on multiple databases using highly sensitive search strategies without language or publication-type restrictions to identify all rct s that are eligible for inclusion. In order to minimize the risk of omitting eligible studies not captured by the original search, they supplemented all electronic searches with manual screening of trial registers and references contained in the included studies. Study selection, data extraction, and risk of bias assessments were performed inde­­pen­dently by two coders using standardized methods to ensure consistency and to eliminate potential errors. Findings from eight rct s involving 6,615 participants were pooled into meta-analyses to calculate the magnitude of effects that mobile text message reminders have on the rate of attendance at healthcare appointments compared to no reminders and phone call reminders.

Meta-analyses are regarded as powerful tools for deriving meaningful conclusions. However, there are situations in which it is neither reasonable nor appropriate to pool studies together using meta-analytic methods simply because there is extensive clinical heterogeneity between the included studies or variation in measurement tools, comparisons, or outcomes of interest. In these cases, systematic reviews can use qualitative synthesis methods such as vote counting, content analysis, classification schemes and tabulations, as an alternative approach to narratively synthesize the results of the independent studies included in the review. This form of review is known as qualitative systematic review.

A rigorous example of one such review in the eHealth domain is presented by Mickan, Atherton, Roberts, Heneghan, and Tilson (2014) on the use of handheld computers by healthcare professionals and their impact on access to information and clinical decision-making. In line with the methodological guide­lines for systematic reviews, these authors: (a) developed and registered with prospero ( www.crd.york.ac.uk/ prospero / ) an a priori review protocol; (b) conducted comprehensive searches for eligible studies using multiple databases and other supplementary strategies (e.g., forward searches); and (c) subsequently carried out study selection, data extraction, and risk of bias assessments in a duplicate manner to eliminate potential errors in the review process. Heterogeneity between the included studies in terms of reported outcomes and measures precluded the use of meta-analytic methods. To this end, the authors resorted to using narrative analysis and synthesis to describe the effectiveness of handheld computers on accessing information for clinical knowledge, adherence to safety and clinical quality guidelines, and diagnostic decision-making.

In recent years, the number of systematic reviews in the field of health informatics has increased considerably. Systematic reviews with discordant findings can cause great confusion and make it difficult for decision-makers to interpret the review-level evidence ( Moher, 2013 ). Therefore, there is a growing need for appraisal and synthesis of prior systematic reviews to ensure that decision-making is constantly informed by the best available accumulated evidence. Umbrella reviews , also known as overviews of systematic reviews, are tertiary types of evidence synthesis that aim to accomplish this; that is, they aim to compare and contrast findings from multiple systematic reviews and meta-analyses ( Becker & Oxman, 2008 ). Umbrella reviews generally adhere to the same principles and rigorous methodological guidelines used in systematic reviews. However, the unit of analysis in umbrella reviews is the systematic review rather than the primary study ( Becker & Oxman, 2008 ). Unlike systematic reviews that have a narrow focus of inquiry, umbrella reviews focus on broader research topics for which there are several potential interventions ( Smith, Devane, Begley, & Clarke, 2011 ). A recent umbrella review on the effects of home telemonitoring interventions for patients with heart failure critically appraised, compared, and synthesized evidence from 15 systematic reviews to investigate which types of home telemonitoring technologies and forms of interventions are more effective in reducing mortality and hospital admissions ( Kitsiou, Paré, & Jaana, 2015 ).

9.3.5. Realist Reviews

Realist reviews are theory-driven interpretative reviews developed to inform, enhance, or supplement conventional systematic reviews by making sense of heterogeneous evidence about complex interventions applied in diverse contexts in a way that informs policy decision-making ( Greenhalgh, Wong, Westhorp, & Pawson, 2011 ). They originated from criticisms of positivist systematic reviews which centre on their “simplistic” underlying assumptions ( Oates, 2011 ). As explained above, systematic reviews seek to identify causation. Such logic is appropriate for fields like medicine and education where findings of randomized controlled trials can be aggregated to see whether a new treatment or intervention does improve outcomes. However, many argue that it is not possible to establish such direct causal links between interventions and outcomes in fields such as social policy, management, and information systems where for any intervention there is unlikely to be a regular or consistent outcome ( Oates, 2011 ; Pawson, 2006 ; Rousseau, Manning, & Denyer, 2008 ).

To circumvent these limitations, Pawson, Greenhalgh, Harvey, and Walshe (2005) have proposed a new approach for synthesizing knowledge that seeks to unpack the mechanism of how “complex interventions” work in particular contexts. The basic research question — what works? — which is usually associated with systematic reviews changes to: what is it about this intervention that works, for whom, in what circumstances, in what respects and why? Realist reviews have no particular preference for either quantitative or qualitative evidence. As a theory-building approach, a realist review usually starts by articulating likely underlying mechanisms and then scrutinizes available evidence to find out whether and where these mechanisms are applicable ( Shepperd et al., 2009 ). Primary studies found in the extant literature are viewed as case studies which can test and modify the initial theories ( Rousseau et al., 2008 ).

The main objective pursued in the realist review conducted by Otte-Trojel, de Bont, Rundall, and van de Klundert (2014) was to examine how patient portals contribute to health service delivery and patient outcomes. The specific goals were to investigate how outcomes are produced and, most importantly, how variations in outcomes can be explained. The research team started with an exploratory review of background documents and research studies to identify ways in which patient portals may contribute to health service delivery and patient outcomes. The authors identified six main ways which represent “educated guesses” to be tested against the data in the evaluation studies. These studies were identified through a formal and systematic search in four databases between 2003 and 2013. Two members of the research team selected the articles using a pre-established list of inclusion and exclusion criteria and following a two-step procedure. The authors then extracted data from the selected articles and created several tables, one for each outcome category. They organized information to bring forward those mechanisms where patient portals contribute to outcomes and the variation in outcomes across different contexts.

9.3.6. Critical Reviews

Lastly, critical reviews aim to provide a critical evaluation and interpretive analysis of existing literature on a particular topic of interest to reveal strengths, weaknesses, contradictions, controversies, inconsistencies, and/or other important issues with respect to theories, hypotheses, research methods or results ( Baumeister & Leary, 1997 ; Kirkevold, 1997 ). Unlike other review types, critical reviews attempt to take a reflective account of the research that has been done in a particular area of interest, and assess its credibility by using appraisal instruments or critical interpretive methods. In this way, critical reviews attempt to constructively inform other scholars about the weaknesses of prior research and strengthen knowledge development by giving focus and direction to studies for further improvement ( Kirkevold, 1997 ).

Kitsiou, Paré, and Jaana (2013) provide an example of a critical review that assessed the methodological quality of prior systematic reviews of home telemonitoring studies for chronic patients. The authors conducted a comprehensive search on multiple databases to identify eligible reviews and subsequently used a validated instrument to conduct an in-depth quality appraisal. Results indicate that the majority of systematic reviews in this particular area suffer from important methodological flaws and biases that impair their internal validity and limit their usefulness for clinical and decision-making purposes. To this end, they provide a number of recommendations to strengthen knowledge development towards improving the design and execution of future reviews on home telemonitoring.

9.4. Summary

Table 9.1 outlines the main types of literature reviews that were described in the previous sub-sections and summarizes the main characteristics that distinguish one review type from another. It also includes key references to methodological guidelines and useful sources that can be used by eHealth scholars and researchers for planning and developing reviews.

Table 9.1. Typology of Literature Reviews (adapted from Paré et al., 2015).

Typology of Literature Reviews (adapted from Paré et al., 2015).

As shown in Table 9.1 , each review type addresses different kinds of research questions or objectives, which subsequently define and dictate the methods and approaches that need to be used to achieve the overarching goal(s) of the review. For example, in the case of narrative reviews, there is greater flexibility in searching and synthesizing articles ( Green et al., 2006 ). Researchers are often relatively free to use a diversity of approaches to search, identify, and select relevant scientific articles, describe their operational characteristics, present how the individual studies fit together, and formulate conclusions. On the other hand, systematic reviews are characterized by their high level of systematicity, rigour, and use of explicit methods, based on an “a priori” review plan that aims to minimize bias in the analysis and synthesis process (Higgins & Green, 2008). Some reviews are exploratory in nature (e.g., scoping/mapping reviews), whereas others may be conducted to discover patterns (e.g., descriptive reviews) or involve a synthesis approach that may include the critical analysis of prior research ( Paré et al., 2015 ). Hence, in order to select the most appropriate type of review, it is critical to know before embarking on a review project, why the research synthesis is conducted and what type of methods are best aligned with the pursued goals.

9.5. Concluding Remarks

In light of the increased use of evidence-based practice and research generating stronger evidence ( Grady et al., 2011 ; Lyden et al., 2013 ), review articles have become essential tools for summarizing, synthesizing, integrating or critically appraising prior knowledge in the eHealth field. As mentioned earlier, when rigorously conducted review articles represent powerful information sources for eHealth scholars and practitioners looking for state-of-the-art evidence. The typology of literature reviews we used herein will allow eHealth researchers, graduate students and practitioners to gain a better understanding of the similarities and differences between review types.

We must stress that this classification scheme does not privilege any specific type of review as being of higher quality than another ( Paré et al., 2015 ). As explained above, each type of review has its own strengths and limitations. Having said that, we realize that the methodological rigour of any review — be it qualitative, quantitative or mixed — is a critical aspect that should be considered seriously by prospective authors. In the present context, the notion of rigour refers to the reliability and validity of the review process described in section 9.2. For one thing, reliability is related to the reproducibility of the review process and steps, which is facilitated by a comprehensive documentation of the literature search process, extraction, coding and analysis performed in the review. Whether the search is comprehensive or not, whether it involves a methodical approach for data extraction and synthesis or not, it is important that the review documents in an explicit and transparent manner the steps and approach that were used in the process of its development. Next, validity characterizes the degree to which the review process was conducted appropriately. It goes beyond documentation and reflects decisions related to the selection of the sources, the search terms used, the period of time covered, the articles selected in the search, and the application of backward and forward searches ( vom Brocke et al., 2009 ). In short, the rigour of any review article is reflected by the explicitness of its methods (i.e., transparency) and the soundness of the approach used. We refer those interested in the concepts of rigour and quality to the work of Templier and Paré (2015) which offers a detailed set of methodological guidelines for conducting and evaluating various types of review articles.

To conclude, our main objective in this chapter was to demystify the various types of literature reviews that are central to the continuous development of the eHealth field. It is our hope that our descriptive account will serve as a valuable source for those conducting, evaluating or using reviews in this important and growing domain.

  • Ammenwerth E., de Keizer N. An inventory of evaluation studies of information technology in health care. Trends in evaluation research, 1982-2002. International Journal of Medical Informatics. 2004; 44 (1):44–56. [ PubMed : 15778794 ]
  • Anderson S., Allen P., Peckham S., Goodwin N. Asking the right questions: scoping studies in the commissioning of research on the organisation and delivery of health services. Health Research Policy and Systems. 2008; 6 (7):1–12. [ PMC free article : PMC2500008 ] [ PubMed : 18613961 ] [ CrossRef ]
  • Archer N., Fevrier-Thomas U., Lokker C., McKibbon K. A., Straus S.E. Personal health records: a scoping review. Journal of American Medical Informatics Association. 2011; 18 (4):515–522. [ PMC free article : PMC3128401 ] [ PubMed : 21672914 ]
  • Arksey H., O’Malley L. Scoping studies: towards a methodological framework. International Journal of Social Research Methodology. 2005; 8 (1):19–32.
  • A systematic, tool-supported method for conducting literature reviews in information systems. Paper presented at the Proceedings of the 19th European Conference on Information Systems ( ecis 2011); June 9 to 11; Helsinki, Finland. 2011.
  • Baumeister R. F., Leary M.R. Writing narrative literature reviews. Review of General Psychology. 1997; 1 (3):311–320.
  • Becker L. A., Oxman A.D. In: Cochrane handbook for systematic reviews of interventions. Higgins J. P. T., Green S., editors. Hoboken, nj : John Wiley & Sons, Ltd; 2008. Overviews of reviews; pp. 607–631.
  • Borenstein M., Hedges L., Higgins J., Rothstein H. Introduction to meta-analysis. Hoboken, nj : John Wiley & Sons Inc; 2009.
  • Cook D. J., Mulrow C. D., Haynes B. Systematic reviews: Synthesis of best evidence for clinical decisions. Annals of Internal Medicine. 1997; 126 (5):376–380. [ PubMed : 9054282 ]
  • Cooper H., Hedges L.V. In: The handbook of research synthesis and meta-analysis. 2nd ed. Cooper H., Hedges L. V., Valentine J. C., editors. New York: Russell Sage Foundation; 2009. Research synthesis as a scientific process; pp. 3–17.
  • Cooper H. M. Organizing knowledge syntheses: A taxonomy of literature reviews. Knowledge in Society. 1988; 1 (1):104–126.
  • Cronin P., Ryan F., Coughlan M. Undertaking a literature review: a step-by-step approach. British Journal of Nursing. 2008; 17 (1):38–43. [ PubMed : 18399395 ]
  • Darlow S., Wen K.Y. Development testing of mobile health interventions for cancer patient self-management: A review. Health Informatics Journal. 2015 (online before print). [ PubMed : 25916831 ] [ CrossRef ]
  • Daudt H. M., van Mossel C., Scott S.J. Enhancing the scoping study methodology: a large, inter-professional team’s experience with Arksey and O’Malley’s framework. bmc Medical Research Methodology. 2013; 13 :48. [ PMC free article : PMC3614526 ] [ PubMed : 23522333 ] [ CrossRef ]
  • Davies P. The relevance of systematic reviews to educational policy and practice. Oxford Review of Education. 2000; 26 (3-4):365–378.
  • Deeks J. J., Higgins J. P. T., Altman D.G. In: Cochrane handbook for systematic reviews of interventions. Higgins J. P. T., Green S., editors. Hoboken, nj : John Wiley & Sons, Ltd; 2008. Analysing data and undertaking meta-analyses; pp. 243–296.
  • Deshazo J. P., Lavallie D. L., Wolf F.M. Publication trends in the medical informatics literature: 20 years of “Medical Informatics” in mesh . bmc Medical Informatics and Decision Making. 2009; 9 :7. [ PMC free article : PMC2652453 ] [ PubMed : 19159472 ] [ CrossRef ]
  • Dixon-Woods M., Agarwal S., Jones D., Young B., Sutton A. Synthesising qualitative and quantitative evidence: a review of possible methods. Journal of Health Services Research and Policy. 2005; 10 (1):45–53. [ PubMed : 15667704 ]
  • Finfgeld-Connett D., Johnson E.D. Literature search strategies for conducting knowledge-building and theory-generating qualitative systematic reviews. Journal of Advanced Nursing. 2013; 69 (1):194–204. [ PMC free article : PMC3424349 ] [ PubMed : 22591030 ]
  • Grady B., Myers K. M., Nelson E. L., Belz N., Bennett L., Carnahan L. … Guidelines Working Group. Evidence-based practice for telemental health. Telemedicine Journal and E Health. 2011; 17 (2):131–148. [ PubMed : 21385026 ]
  • Green B. N., Johnson C. D., Adams A. Writing narrative literature reviews for peer-reviewed journals: secrets of the trade. Journal of Chiropractic Medicine. 2006; 5 (3):101–117. [ PMC free article : PMC2647067 ] [ PubMed : 19674681 ]
  • Greenhalgh T., Wong G., Westhorp G., Pawson R. Protocol–realist and meta-narrative evidence synthesis: evolving standards ( rameses ). bmc Medical Research Methodology. 2011; 11 :115. [ PMC free article : PMC3173389 ] [ PubMed : 21843376 ]
  • Gurol-Urganci I., de Jongh T., Vodopivec-Jamsek V., Atun R., Car J. Mobile phone messaging reminders for attendance at healthcare appointments. Cochrane Database System Review. 2013; 12 cd 007458. [ PMC free article : PMC6485985 ] [ PubMed : 24310741 ] [ CrossRef ]
  • Hart C. Doing a literature review: Releasing the social science research imagination. London: SAGE Publications; 1998.
  • Higgins J. P. T., Green S., editors. Cochrane handbook for systematic reviews of interventions: Cochrane book series. Hoboken, nj : Wiley-Blackwell; 2008.
  • Jesson J., Matheson L., Lacey F.M. Doing your literature review: traditional and systematic techniques. Los Angeles & London: SAGE Publications; 2011.
  • King W. R., He J. Understanding the role and methods of meta-analysis in IS research. Communications of the Association for Information Systems. 2005; 16 :1.
  • Kirkevold M. Integrative nursing research — an important strategy to further the development of nursing science and nursing practice. Journal of Advanced Nursing. 1997; 25 (5):977–984. [ PubMed : 9147203 ]
  • Kitchenham B., Charters S. ebse Technical Report Version 2.3. Keele & Durham. uk : Keele University & University of Durham; 2007. Guidelines for performing systematic literature reviews in software engineering.
  • Kitsiou S., Paré G., Jaana M. Systematic reviews and meta-analyses of home telemonitoring interventions for patients with chronic diseases: a critical assessment of their methodological quality. Journal of Medical Internet Research. 2013; 15 (7):e150. [ PMC free article : PMC3785977 ] [ PubMed : 23880072 ]
  • Kitsiou S., Paré G., Jaana M. Effects of home telemonitoring interventions on patients with chronic heart failure: an overview of systematic reviews. Journal of Medical Internet Research. 2015; 17 (3):e63. [ PMC free article : PMC4376138 ] [ PubMed : 25768664 ]
  • Levac D., Colquhoun H., O’Brien K. K. Scoping studies: advancing the methodology. Implementation Science. 2010; 5 (1):69. [ PMC free article : PMC2954944 ] [ PubMed : 20854677 ]
  • Levy Y., Ellis T.J. A systems approach to conduct an effective literature review in support of information systems research. Informing Science. 2006; 9 :181–211.
  • Liberati A., Altman D. G., Tetzlaff J., Mulrow C., Gøtzsche P. C., Ioannidis J. P. A. et al. Moher D. The prisma statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. Annals of Internal Medicine. 2009; 151 (4):W-65. [ PubMed : 19622512 ]
  • Lyden J. R., Zickmund S. L., Bhargava T. D., Bryce C. L., Conroy M. B., Fischer G. S. et al. McTigue K. M. Implementing health information technology in a patient-centered manner: Patient experiences with an online evidence-based lifestyle intervention. Journal for Healthcare Quality. 2013; 35 (5):47–57. [ PubMed : 24004039 ]
  • Mickan S., Atherton H., Roberts N. W., Heneghan C., Tilson J.K. Use of handheld computers in clinical practice: a systematic review. bmc Medical Informatics and Decision Making. 2014; 14 :56. [ PMC free article : PMC4099138 ] [ PubMed : 24998515 ]
  • Moher D. The problem of duplicate systematic reviews. British Medical Journal. 2013; 347 (5040) [ PubMed : 23945367 ] [ CrossRef ]
  • Montori V. M., Wilczynski N. L., Morgan D., Haynes R. B., Hedges T. Systematic reviews: a cross-sectional study of location and citation counts. bmc Medicine. 2003; 1 :2. [ PMC free article : PMC281591 ] [ PubMed : 14633274 ]
  • Mulrow C. D. The medical review article: state of the science. Annals of Internal Medicine. 1987; 106 (3):485–488. [ PubMed : 3813259 ] [ CrossRef ]
  • Evidence-based information systems: A decade later. Proceedings of the European Conference on Information Systems ; 2011. Retrieved from http://aisel ​.aisnet.org/cgi/viewcontent ​.cgi?article ​=1221&context ​=ecis2011 .
  • Okoli C., Schabram K. A guide to conducting a systematic literature review of information systems research. ssrn Electronic Journal. 2010
  • Otte-Trojel T., de Bont A., Rundall T. G., van de Klundert J. How outcomes are achieved through patient portals: a realist review. Journal of American Medical Informatics Association. 2014; 21 (4):751–757. [ PMC free article : PMC4078283 ] [ PubMed : 24503882 ]
  • Paré G., Trudel M.-C., Jaana M., Kitsiou S. Synthesizing information systems knowledge: A typology of literature reviews. Information & Management. 2015; 52 (2):183–199.
  • Patsopoulos N. A., Analatos A. A., Ioannidis J.P. A. Relative citation impact of various study designs in the health sciences. Journal of the American Medical Association. 2005; 293 (19):2362–2366. [ PubMed : 15900006 ]
  • Paul M. M., Greene C. M., Newton-Dame R., Thorpe L. E., Perlman S. E., McVeigh K. H., Gourevitch M.N. The state of population health surveillance using electronic health records: A narrative review. Population Health Management. 2015; 18 (3):209–216. [ PubMed : 25608033 ]
  • Pawson R. Evidence-based policy: a realist perspective. London: SAGE Publications; 2006.
  • Pawson R., Greenhalgh T., Harvey G., Walshe K. Realist review—a new method of systematic review designed for complex policy interventions. Journal of Health Services Research & Policy. 2005; 10 (Suppl 1):21–34. [ PubMed : 16053581 ]
  • Petersen K., Vakkalanka S., Kuzniarz L. Guidelines for conducting systematic mapping studies in software engineering: An update. Information and Software Technology. 2015; 64 :1–18.
  • Petticrew M., Roberts H. Systematic reviews in the social sciences: A practical guide. Malden, ma : Blackwell Publishing Co; 2006.
  • Rousseau D. M., Manning J., Denyer D. Evidence in management and organizational science: Assembling the field’s full weight of scientific knowledge through syntheses. The Academy of Management Annals. 2008; 2 (1):475–515.
  • Rowe F. What literature review is not: diversity, boundaries and recommendations. European Journal of Information Systems. 2014; 23 (3):241–255.
  • Shea B. J., Hamel C., Wells G. A., Bouter L. M., Kristjansson E., Grimshaw J. et al. Boers M. amstar is a reliable and valid measurement tool to assess the methodological quality of systematic reviews. Journal of Clinical Epidemiology. 2009; 62 (10):1013–1020. [ PubMed : 19230606 ]
  • Shepperd S., Lewin S., Straus S., Clarke M., Eccles M. P., Fitzpatrick R. et al. Sheikh A. Can we systematically review studies that evaluate complex interventions? PLoS Medicine. 2009; 6 (8):e1000086. [ PMC free article : PMC2717209 ] [ PubMed : 19668360 ]
  • Silva B. M., Rodrigues J. J., de la Torre Díez I., López-Coronado M., Saleem K. Mobile-health: A review of current state in 2015. Journal of Biomedical Informatics. 2015; 56 :265–272. [ PubMed : 26071682 ]
  • Smith V., Devane D., Begley C., Clarke M. Methodology in conducting a systematic review of systematic reviews of healthcare interventions. bmc Medical Research Methodology. 2011; 11 (1):15. [ PMC free article : PMC3039637 ] [ PubMed : 21291558 ]
  • Sylvester A., Tate M., Johnstone D. Beyond synthesis: re-presenting heterogeneous research literature. Behaviour & Information Technology. 2013; 32 (12):1199–1215.
  • Templier M., Paré G. A framework for guiding and evaluating literature reviews. Communications of the Association for Information Systems. 2015; 37 (6):112–137.
  • Thomas J., Harden A. Methods for the thematic synthesis of qualitative research in systematic reviews. bmc Medical Research Methodology. 2008; 8 (1):45. [ PMC free article : PMC2478656 ] [ PubMed : 18616818 ]
  • Reconstructing the giant: on the importance of rigour in documenting the literature search process. Paper presented at the Proceedings of the 17th European Conference on Information Systems ( ecis 2009); Verona, Italy. 2009.
  • Webster J., Watson R.T. Analyzing the past to prepare for the future: Writing a literature review. Management Information Systems Quarterly. 2002; 26 (2):11.
  • Whitlock E. P., Lin J. S., Chou R., Shekelle P., Robinson K.A. Using existing systematic reviews in complex systematic reviews. Annals of Internal Medicine. 2008; 148 (10):776–782. [ PubMed : 18490690 ]

This publication is licensed under a Creative Commons License, Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0): see https://creativecommons.org/licenses/by-nc/4.0/

  • Cite this Page Paré G, Kitsiou S. Chapter 9 Methods for Literature Reviews. In: Lau F, Kuziemsky C, editors. Handbook of eHealth Evaluation: An Evidence-based Approach [Internet]. Victoria (BC): University of Victoria; 2017 Feb 27.
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What is a literature review?

A literature review is an integrated analysis -- not just a summary-- of scholarly writings and other relevant evidence related directly to your research question.  That is, it represents a synthesis of the evidence that provides background information on your topic and shows a association between the evidence and your research question.

A literature review may be a stand alone work or the introduction to a larger research paper, depending on the assignment.  Rely heavily on the guidelines your instructor has given you.

Why is it important?

A literature review is important because it:

  • Explains the background of research on a topic.
  • Demonstrates why a topic is significant to a subject area.
  • Discovers relationships between research studies/ideas.
  • Identifies major themes, concepts, and researchers on a topic.
  • Identifies critical gaps and points of disagreement.
  • Discusses further research questions that logically come out of the previous studies.

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1. Choose a topic. Define your research question.

Your literature review should be guided by your central research question.  The literature represents background and research developments related to a specific research question, interpreted and analyzed by you in a synthesized way.

  • Make sure your research question is not too broad or too narrow.  Is it manageable?
  • Begin writing down terms that are related to your question. These will be useful for searches later.
  • If you have the opportunity, discuss your topic with your professor and your class mates.

2. Decide on the scope of your review

How many studies do you need to look at? How comprehensive should it be? How many years should it cover? 

  • This may depend on your assignment.  How many sources does the assignment require?

3. Select the databases you will use to conduct your searches.

Make a list of the databases you will search. 

Where to find databases:

  • use the tabs on this guide
  • Find other databases in the Nursing Information Resources web page
  • More on the Medical Library web page
  • ... and more on the Yale University Library web page

4. Conduct your searches to find the evidence. Keep track of your searches.

  • Use the key words in your question, as well as synonyms for those words, as terms in your search. Use the database tutorials for help.
  • Save the searches in the databases. This saves time when you want to redo, or modify, the searches. It is also helpful to use as a guide is the searches are not finding any useful results.
  • Review the abstracts of research studies carefully. This will save you time.
  • Use the bibliographies and references of research studies you find to locate others.
  • Check with your professor, or a subject expert in the field, if you are missing any key works in the field.
  • Ask your librarian for help at any time.
  • Use a citation manager, such as EndNote as the repository for your citations. See the EndNote tutorials for help.

Review the literature

Some questions to help you analyze the research:

  • What was the research question of the study you are reviewing? What were the authors trying to discover?
  • Was the research funded by a source that could influence the findings?
  • What were the research methodologies? Analyze its literature review, the samples and variables used, the results, and the conclusions.
  • Does the research seem to be complete? Could it have been conducted more soundly? What further questions does it raise?
  • If there are conflicting studies, why do you think that is?
  • How are the authors viewed in the field? Has this study been cited? If so, how has it been analyzed?

Tips: 

  • Review the abstracts carefully.  
  • Keep careful notes so that you may track your thought processes during the research process.
  • Create a matrix of the studies for easy analysis, and synthesis, across all of the studies.
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How To Structure Your Literature Review

3 options to help structure your chapter.

By: Amy Rommelspacher (PhD) | Reviewer: Dr Eunice Rautenbach | November 2020 (Updated May 2023)

Writing the literature review chapter can seem pretty daunting when you’re piecing together your dissertation or thesis. As  we’ve discussed before , a good literature review needs to achieve a few very important objectives – it should:

  • Demonstrate your knowledge of the research topic
  • Identify the gaps in the literature and show how your research links to these
  • Provide the foundation for your conceptual framework (if you have one)
  • Inform your own  methodology and research design

To achieve this, your literature review needs a well-thought-out structure . Get the structure of your literature review chapter wrong and you’ll struggle to achieve these objectives. Don’t worry though – in this post, we’ll look at how to structure your literature review for maximum impact (and marks!).

The function of the lit review

But wait – is this the right time?

Deciding on the structure of your literature review should come towards the end of the literature review process – after you have collected and digested the literature, but before you start writing the chapter. 

In other words, you need to first develop a rich understanding of the literature before you even attempt to map out a structure. There’s no use trying to develop a structure before you’ve fully wrapped your head around the existing research.

Equally importantly, you need to have a structure in place before you start writing , or your literature review will most likely end up a rambling, disjointed mess. 

Importantly, don’t feel that once you’ve defined a structure you can’t iterate on it. It’s perfectly natural to adjust as you engage in the writing process. As we’ve discussed before , writing is a way of developing your thinking, so it’s quite common for your thinking to change – and therefore, for your chapter structure to change – as you write. 

Need a helping hand?

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Like any other chapter in your thesis or dissertation, your literature review needs to have a clear, logical structure. At a minimum, it should have three essential components – an  introduction , a  body   and a  conclusion . 

Let’s take a closer look at each of these.

1: The Introduction Section

Just like any good introduction, the introduction section of your literature review should introduce the purpose and layout (organisation) of the chapter. In other words, your introduction needs to give the reader a taste of what’s to come, and how you’re going to lay that out. Essentially, you should provide the reader with a high-level roadmap of your chapter to give them a taste of the journey that lies ahead.

Here’s an example of the layout visualised in a literature review introduction:

Example of literature review outline structure

Your introduction should also outline your topic (including any tricky terminology or jargon) and provide an explanation of the scope of your literature review – in other words, what you  will   and  won’t   be covering (the delimitations ). This helps ringfence your review and achieve a clear focus . The clearer and narrower your focus, the deeper you can dive into the topic (which is typically where the magic lies). 

Depending on the nature of your project, you could also present your stance or point of view at this stage. In other words, after grappling with the literature you’ll have an opinion about what the trends and concerns are in the field as well as what’s lacking. The introduction section can then present these ideas so that it is clear to examiners that you’re aware of how your research connects with existing knowledge .

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2: The Body Section

The body of your literature review is the centre of your work. This is where you’ll present, analyse, evaluate and synthesise the existing research. In other words, this is where you’re going to earn (or lose) the most marks. Therefore, it’s important to carefully think about how you will organise your discussion to present it in a clear way. 

The body of your literature review should do just as the description of this chapter suggests. It should “review” the literature – in other words, identify, analyse, and synthesise it. So, when thinking about structuring your literature review, you need to think about which structural approach will provide the best “review” for your specific type of research and objectives (we’ll get to this shortly).

There are (broadly speaking)  three options  for organising your literature review.

The body section of your literature review is the where you'll present, analyse, evaluate and synthesise the existing research.

Option 1: Chronological (according to date)

Organising the literature chronologically is one of the simplest ways to structure your literature review. You start with what was published first and work your way through the literature until you reach the work published most recently. Pretty straightforward.

The benefit of this option is that it makes it easy to discuss the developments and debates in the field as they emerged over time. Organising your literature chronologically also allows you to highlight how specific articles or pieces of work might have changed the course of the field – in other words, which research has had the most impact . Therefore, this approach is very useful when your research is aimed at understanding how the topic has unfolded over time and is often used by scholars in the field of history. That said, this approach can be utilised by anyone that wants to explore change over time .

Adopting the chronological structure allows you to discuss the developments and debates in the field as they emerged over time.

For example , if a student of politics is investigating how the understanding of democracy has evolved over time, they could use the chronological approach to provide a narrative that demonstrates how this understanding has changed through the ages.

Here are some questions you can ask yourself to help you structure your literature review chronologically.

  • What is the earliest literature published relating to this topic?
  • How has the field changed over time? Why?
  • What are the most recent discoveries/theories?

In some ways, chronology plays a part whichever way you decide to structure your literature review, because you will always, to a certain extent, be analysing how the literature has developed. However, with the chronological approach, the emphasis is very firmly on how the discussion has evolved over time , as opposed to how all the literature links together (which we’ll discuss next ).

Option 2: Thematic (grouped by theme)

The thematic approach to structuring a literature review means organising your literature by theme or category – for example, by independent variables (i.e. factors that have an impact on a specific outcome).

As you’ve been collecting and synthesising literature , you’ll likely have started seeing some themes or patterns emerging. You can then use these themes or patterns as a structure for your body discussion. The thematic approach is the most common approach and is useful for structuring literature reviews in most fields.

For example, if you were researching which factors contributed towards people trusting an organisation, you might find themes such as consumers’ perceptions of an organisation’s competence, benevolence and integrity. Structuring your literature review thematically would mean structuring your literature review’s body section to discuss each of these themes, one section at a time.

The thematic structure allows you to organise your literature by theme or category  – e.g. by independent variables.

Here are some questions to ask yourself when structuring your literature review by themes:

  • Are there any patterns that have come to light in the literature?
  • What are the central themes and categories used by the researchers?
  • Do I have enough evidence of these themes?

PS – you can see an example of a thematically structured literature review in our literature review sample walkthrough video here.

Option 3: Methodological

The methodological option is a way of structuring your literature review by the research methodologies used . In other words, organising your discussion based on the angle from which each piece of research was approached – for example, qualitative , quantitative or mixed  methodologies.

Structuring your literature review by methodology can be useful if you are drawing research from a variety of disciplines and are critiquing different methodologies. The point of this approach is to question  how  existing research has been conducted, as opposed to  what  the conclusions and/or findings the research were.

The methodological structure allows you to organise your chapter by the analysis method  used - e.g. qual, quant or mixed.

For example, a sociologist might centre their research around critiquing specific fieldwork practices. Their literature review will then be a summary of the fieldwork methodologies used by different studies.

Here are some questions you can ask yourself when structuring your literature review according to methodology:

  • Which methodologies have been utilised in this field?
  • Which methodology is the most popular (and why)?
  • What are the strengths and weaknesses of the various methodologies?
  • How can the existing methodologies inform my own methodology?

3: The Conclusion Section

Once you’ve completed the body section of your literature review using one of the structural approaches we discussed above, you’ll need to “wrap up” your literature review and pull all the pieces together to set the direction for the rest of your dissertation or thesis.

The conclusion is where you’ll present the key findings of your literature review. In this section, you should emphasise the research that is especially important to your research questions and highlight the gaps that exist in the literature. Based on this, you need to make it clear what you will add to the literature – in other words, justify your own research by showing how it will help fill one or more of the gaps you just identified.

Last but not least, if it’s your intention to develop a conceptual framework for your dissertation or thesis, the conclusion section is a good place to present this.

In the conclusion section, you’ll need to present the key findings of your literature review and highlight the gaps that exist in the literature. Based on this, you'll  need to make it clear what your study will add  to the literature.

Example: Thematically Structured Review

In the video below, we unpack a literature review chapter so that you can see an example of a thematically structure review in practice.

Let’s Recap

In this article, we’ve  discussed how to structure your literature review for maximum impact. Here’s a quick recap of what  you need to keep in mind when deciding on your literature review structure:

  • Just like other chapters, your literature review needs a clear introduction , body and conclusion .
  • The introduction section should provide an overview of what you will discuss in your literature review.
  • The body section of your literature review can be organised by chronology , theme or methodology . The right structural approach depends on what you’re trying to achieve with your research.
  • The conclusion section should draw together the key findings of your literature review and link them to your research questions.

If you’re ready to get started, be sure to download our free literature review template to fast-track your chapter outline.

Literature Review Course

Psst… there’s more!

This post is an extract from our bestselling Udemy Course, Literature Review Bootcamp . If you want to work smart, you don't want to miss this .

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Literature review 101 - how to find articles

27 Comments

Marin

Great work. This is exactly what I was looking for and helps a lot together with your previous post on literature review. One last thing is missing: a link to a great literature chapter of an journal article (maybe with comments of the different sections in this review chapter). Do you know any great literature review chapters?

ISHAYA JEREMIAH AYOCK

I agree with you Marin… A great piece

Qaiser

I agree with Marin. This would be quite helpful if you annotate a nicely structured literature from previously published research articles.

Maurice Kagwi

Awesome article for my research.

Ache Roland Ndifor

I thank you immensely for this wonderful guide

Malik Imtiaz Ahmad

It is indeed thought and supportive work for the futurist researcher and students

Franklin Zon

Very educative and good time to get guide. Thank you

Dozie

Great work, very insightful. Thank you.

KAWU ALHASSAN

Thanks for this wonderful presentation. My question is that do I put all the variables into a single conceptual framework or each hypothesis will have it own conceptual framework?

CYRUS ODUAH

Thank you very much, very helpful

Michael Sanya Oluyede

This is very educative and precise . Thank you very much for dropping this kind of write up .

Karla Buchanan

Pheeww, so damn helpful, thank you for this informative piece.

Enang Lazarus

I’m doing a research project topic ; stool analysis for parasitic worm (enteric) worm, how do I structure it, thanks.

Biswadeb Dasgupta

comprehensive explanation. Help us by pasting the URL of some good “literature review” for better understanding.

Vik

great piece. thanks for the awesome explanation. it is really worth sharing. I have a little question, if anyone can help me out, which of the options in the body of literature can be best fit if you are writing an architectural thesis that deals with design?

S Dlamini

I am doing a research on nanofluids how can l structure it?

PATRICK MACKARNESS

Beautifully clear.nThank you!

Lucid! Thankyou!

Abraham

Brilliant work, well understood, many thanks

Nour

I like how this was so clear with simple language 😊😊 thank you so much 😊 for these information 😊

Lindiey

Insightful. I was struggling to come up with a sensible literature review but this has been really helpful. Thank you!

NAGARAJU K

You have given thought-provoking information about the review of the literature.

Vakaloloma

Thank you. It has made my own research better and to impart your work to students I teach

Alphonse NSHIMIYIMANA

I learnt a lot from this teaching. It’s a great piece.

Resa

I am doing research on EFL teacher motivation for his/her job. How Can I structure it? Is there any detailed template, additional to this?

Gerald Gormanous

You are so cool! I do not think I’ve read through something like this before. So nice to find somebody with some genuine thoughts on this issue. Seriously.. thank you for starting this up. This site is one thing that is required on the internet, someone with a little originality!

kan

I’m asked to do conceptual, theoretical and empirical literature, and i just don’t know how to structure it

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Literature review

A general guide on how to conduct and write a literature review.

Please check course or programme information and materials provided by teaching staff , including your project supervisor, for subject-specific guidance.

What is a literature review?

A literature review is a piece of academic writing demonstrating knowledge and understanding of the academic literature on a specific topic placed in context.  A literature review also includes a critical evaluation of the material; this is why it is called a literature review rather than a literature report. It is a process of reviewing the literature, as well as a form of writing.

To illustrate the difference between reporting and reviewing, think about television or film review articles.  These articles include content such as a brief synopsis or the key points of the film or programme plus the critic’s own evaluation.  Similarly the two main objectives of a literature review are firstly the content covering existing research, theories and evidence, and secondly your own critical evaluation and discussion of this content. 

Usually a literature review forms a section or part of a dissertation, research project or long essay.  However, it can also be set and assessed as a standalone piece of work.

What is the purpose of a literature review?

…your task is to build an argument, not a library. Rudestam, K.E. and Newton, R.R. (1992) Surviving your dissertation: A comprehensive guide to content and process. California: Sage, p49.

In a larger piece of written work, such as a dissertation or project, a literature review is usually one of the first tasks carried out after deciding on a topic.  Reading combined with critical analysis can help to refine a topic and frame research questions.  Conducting a literature review establishes your familiarity with and understanding of current research in a particular field before carrying out a new investigation.  After doing a literature review, you should know what research has already been done and be able to identify what is unknown within your topic.

When doing and writing a literature review, it is good practice to:

  • summarise and analyse previous research and theories;
  • identify areas of controversy and contested claims;
  • highlight any gaps that may exist in research to date.

Conducting a literature review

Focusing on different aspects of your literature review can be useful to help plan, develop, refine and write it.  You can use and adapt the prompt questions in our worksheet below at different points in the process of researching and writing your review.  These are suggestions to get you thinking and writing.

Developing and refining your literature review (pdf)

Developing and refining your literature review (Word)

Developing and refining your literature review (Word rtf)

Writing a literature review has a lot in common with other assignment tasks.  There is advice on our other pages about thinking critically, reading strategies and academic writing.  Our literature review top tips suggest some specific things you can do to help you submit a successful review.

Literature review top tips (pdf)

Literature review top tips (Word rtf)

Our reading page includes strategies and advice on using books and articles and a notes record sheet grid you can use.

Reading at university

The Academic writing page suggests ways to organise and structure information from a range of sources and how you can develop your argument as you read and write.

Academic writing

The Critical thinking page has advice on how to be a more critical researcher and a form you can use to help you think and break down the stages of developing your argument.

Critical thinking

As with other forms of academic writing, your literature review needs to demonstrate good academic practice by following the Code of Student Conduct and acknowledging the work of others through citing and referencing your sources.  

Good academic practice

As with any writing task, you will need to review, edit and rewrite sections of your literature review.  The Editing and proofreading page includes tips on how to do this and strategies for standing back and thinking about your structure and checking the flow of your argument.

Editing and proofreading

Guidance on literature searching from the University Library

The Academic Support Librarians have developed LibSmart I and II, Learn courses to help you develop and enhance your digital research skills and capabilities; from getting started with the Library to managing data for your dissertation.

Searching using the library’s DiscoverEd tool: DiscoverEd

Finding resources in your subject: Subject guides

The Academic Support Librarians also provide one-to-one appointments to help you develop your research strategies.

1 to 1 support for literature searching and systematic reviews

Advice to help you optimise use of Google Scholar, Google Books and Google for your research and study: Using Google

Managing and curating your references

A referencing management tool can help you to collect and organise and your source material to produce a bibliography or reference list. 

Referencing and reference management

Information Services provide access to Cite them right online which is a guide to the main referencing systems and tells you how to reference just about any source (EASE log-in may be required).

Cite them right

Published study guides

There are a number of scholarship skills books and guides available which can help with writing a literature review.  Our Resource List of study skills guides includes sections on Referencing, Dissertation and project writing and Literature reviews.

Study skills guides

  • USC Libraries
  • Research Guides

Organizing Your Social Sciences Research Paper

  • 5. The Literature Review
  • Purpose of Guide
  • Design Flaws to Avoid
  • Independent and Dependent Variables
  • Glossary of Research Terms
  • Reading Research Effectively
  • Narrowing a Topic Idea
  • Broadening a Topic Idea
  • Extending the Timeliness of a Topic Idea
  • Academic Writing Style
  • Choosing a Title
  • Making an Outline
  • Paragraph Development
  • Research Process Video Series
  • Executive Summary
  • The C.A.R.S. Model
  • Background Information
  • The Research Problem/Question
  • Theoretical Framework
  • Citation Tracking
  • Content Alert Services
  • Evaluating Sources
  • Primary Sources
  • Secondary Sources
  • Tiertiary Sources
  • Scholarly vs. Popular Publications
  • Qualitative Methods
  • Quantitative Methods
  • Insiderness
  • Using Non-Textual Elements
  • Limitations of the Study
  • Common Grammar Mistakes
  • Writing Concisely
  • Avoiding Plagiarism
  • Footnotes or Endnotes?
  • Further Readings
  • Generative AI and Writing
  • USC Libraries Tutorials and Other Guides
  • Bibliography

A literature review surveys prior research published in books, scholarly articles, and any other sources relevant to a particular issue, area of research, or theory, and by so doing, provides a description, summary, and critical evaluation of these works in relation to the research problem being investigated. Literature reviews are designed to provide an overview of sources you have used in researching a particular topic and to demonstrate to your readers how your research fits within existing scholarship about the topic.

Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . Fourth edition. Thousand Oaks, CA: SAGE, 2014.

Importance of a Good Literature Review

A literature review may consist of simply a summary of key sources, but in the social sciences, a literature review usually has an organizational pattern and combines both summary and synthesis, often within specific conceptual categories . A summary is a recap of the important information of the source, but a synthesis is a re-organization, or a reshuffling, of that information in a way that informs how you are planning to investigate a research problem. The analytical features of a literature review might:

  • Give a new interpretation of old material or combine new with old interpretations,
  • Trace the intellectual progression of the field, including major debates,
  • Depending on the situation, evaluate the sources and advise the reader on the most pertinent or relevant research, or
  • Usually in the conclusion of a literature review, identify where gaps exist in how a problem has been researched to date.

Given this, the purpose of a literature review is to:

  • Place each work in the context of its contribution to understanding the research problem being studied.
  • Describe the relationship of each work to the others under consideration.
  • Identify new ways to interpret prior research.
  • Reveal any gaps that exist in the literature.
  • Resolve conflicts amongst seemingly contradictory previous studies.
  • Identify areas of prior scholarship to prevent duplication of effort.
  • Point the way in fulfilling a need for additional research.
  • Locate your own research within the context of existing literature [very important].

Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper. 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Jesson, Jill. Doing Your Literature Review: Traditional and Systematic Techniques . Los Angeles, CA: SAGE, 2011; Knopf, Jeffrey W. "Doing a Literature Review." PS: Political Science and Politics 39 (January 2006): 127-132; Ridley, Diana. The Literature Review: A Step-by-Step Guide for Students . 2nd ed. Los Angeles, CA: SAGE, 2012.

Types of Literature Reviews

It is important to think of knowledge in a given field as consisting of three layers. First, there are the primary studies that researchers conduct and publish. Second are the reviews of those studies that summarize and offer new interpretations built from and often extending beyond the primary studies. Third, there are the perceptions, conclusions, opinion, and interpretations that are shared informally among scholars that become part of the body of epistemological traditions within the field.

In composing a literature review, it is important to note that it is often this third layer of knowledge that is cited as "true" even though it often has only a loose relationship to the primary studies and secondary literature reviews. Given this, while literature reviews are designed to provide an overview and synthesis of pertinent sources you have explored, there are a number of approaches you could adopt depending upon the type of analysis underpinning your study.

Argumentative Review This form examines literature selectively in order to support or refute an argument, deeply embedded assumption, or philosophical problem already established in the literature. The purpose is to develop a body of literature that establishes a contrarian viewpoint. Given the value-laden nature of some social science research [e.g., educational reform; immigration control], argumentative approaches to analyzing the literature can be a legitimate and important form of discourse. However, note that they can also introduce problems of bias when they are used to make summary claims of the sort found in systematic reviews [see below].

Integrative Review Considered a form of research that reviews, critiques, and synthesizes representative literature on a topic in an integrated way such that new frameworks and perspectives on the topic are generated. The body of literature includes all studies that address related or identical hypotheses or research problems. A well-done integrative review meets the same standards as primary research in regard to clarity, rigor, and replication. This is the most common form of review in the social sciences.

Historical Review Few things rest in isolation from historical precedent. Historical literature reviews focus on examining research throughout a period of time, often starting with the first time an issue, concept, theory, phenomena emerged in the literature, then tracing its evolution within the scholarship of a discipline. The purpose is to place research in a historical context to show familiarity with state-of-the-art developments and to identify the likely directions for future research.

Methodological Review A review does not always focus on what someone said [findings], but how they came about saying what they say [method of analysis]. Reviewing methods of analysis provides a framework of understanding at different levels [i.e. those of theory, substantive fields, research approaches, and data collection and analysis techniques], how researchers draw upon a wide variety of knowledge ranging from the conceptual level to practical documents for use in fieldwork in the areas of ontological and epistemological consideration, quantitative and qualitative integration, sampling, interviewing, data collection, and data analysis. This approach helps highlight ethical issues which you should be aware of and consider as you go through your own study.

Systematic Review This form consists of an overview of existing evidence pertinent to a clearly formulated research question, which uses pre-specified and standardized methods to identify and critically appraise relevant research, and to collect, report, and analyze data from the studies that are included in the review. The goal is to deliberately document, critically evaluate, and summarize scientifically all of the research about a clearly defined research problem . Typically it focuses on a very specific empirical question, often posed in a cause-and-effect form, such as "To what extent does A contribute to B?" This type of literature review is primarily applied to examining prior research studies in clinical medicine and allied health fields, but it is increasingly being used in the social sciences.

Theoretical Review The purpose of this form is to examine the corpus of theory that has accumulated in regard to an issue, concept, theory, phenomena. The theoretical literature review helps to establish what theories already exist, the relationships between them, to what degree the existing theories have been investigated, and to develop new hypotheses to be tested. Often this form is used to help establish a lack of appropriate theories or reveal that current theories are inadequate for explaining new or emerging research problems. The unit of analysis can focus on a theoretical concept or a whole theory or framework.

NOTE : Most often the literature review will incorporate some combination of types. For example, a review that examines literature supporting or refuting an argument, assumption, or philosophical problem related to the research problem will also need to include writing supported by sources that establish the history of these arguments in the literature.

Baumeister, Roy F. and Mark R. Leary. "Writing Narrative Literature Reviews."  Review of General Psychology 1 (September 1997): 311-320; Mark R. Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Kennedy, Mary M. "Defining a Literature." Educational Researcher 36 (April 2007): 139-147; Petticrew, Mark and Helen Roberts. Systematic Reviews in the Social Sciences: A Practical Guide . Malden, MA: Blackwell Publishers, 2006; Torracro, Richard. "Writing Integrative Literature Reviews: Guidelines and Examples." Human Resource Development Review 4 (September 2005): 356-367; Rocco, Tonette S. and Maria S. Plakhotnik. "Literature Reviews, Conceptual Frameworks, and Theoretical Frameworks: Terms, Functions, and Distinctions." Human Ressource Development Review 8 (March 2008): 120-130; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016.

Structure and Writing Style

I.  Thinking About Your Literature Review

The structure of a literature review should include the following in support of understanding the research problem :

  • An overview of the subject, issue, or theory under consideration, along with the objectives of the literature review,
  • Division of works under review into themes or categories [e.g. works that support a particular position, those against, and those offering alternative approaches entirely],
  • An explanation of how each work is similar to and how it varies from the others,
  • Conclusions as to which pieces are best considered in their argument, are most convincing of their opinions, and make the greatest contribution to the understanding and development of their area of research.

The critical evaluation of each work should consider :

  • Provenance -- what are the author's credentials? Are the author's arguments supported by evidence [e.g. primary historical material, case studies, narratives, statistics, recent scientific findings]?
  • Methodology -- were the techniques used to identify, gather, and analyze the data appropriate to addressing the research problem? Was the sample size appropriate? Were the results effectively interpreted and reported?
  • Objectivity -- is the author's perspective even-handed or prejudicial? Is contrary data considered or is certain pertinent information ignored to prove the author's point?
  • Persuasiveness -- which of the author's theses are most convincing or least convincing?
  • Validity -- are the author's arguments and conclusions convincing? Does the work ultimately contribute in any significant way to an understanding of the subject?

II.  Development of the Literature Review

Four Basic Stages of Writing 1.  Problem formulation -- which topic or field is being examined and what are its component issues? 2.  Literature search -- finding materials relevant to the subject being explored. 3.  Data evaluation -- determining which literature makes a significant contribution to the understanding of the topic. 4.  Analysis and interpretation -- discussing the findings and conclusions of pertinent literature.

Consider the following issues before writing the literature review: Clarify If your assignment is not specific about what form your literature review should take, seek clarification from your professor by asking these questions: 1.  Roughly how many sources would be appropriate to include? 2.  What types of sources should I review (books, journal articles, websites; scholarly versus popular sources)? 3.  Should I summarize, synthesize, or critique sources by discussing a common theme or issue? 4.  Should I evaluate the sources in any way beyond evaluating how they relate to understanding the research problem? 5.  Should I provide subheadings and other background information, such as definitions and/or a history? Find Models Use the exercise of reviewing the literature to examine how authors in your discipline or area of interest have composed their literature review sections. Read them to get a sense of the types of themes you might want to look for in your own research or to identify ways to organize your final review. The bibliography or reference section of sources you've already read, such as required readings in the course syllabus, are also excellent entry points into your own research. Narrow the Topic The narrower your topic, the easier it will be to limit the number of sources you need to read in order to obtain a good survey of relevant resources. Your professor will probably not expect you to read everything that's available about the topic, but you'll make the act of reviewing easier if you first limit scope of the research problem. A good strategy is to begin by searching the USC Libraries Catalog for recent books about the topic and review the table of contents for chapters that focuses on specific issues. You can also review the indexes of books to find references to specific issues that can serve as the focus of your research. For example, a book surveying the history of the Israeli-Palestinian conflict may include a chapter on the role Egypt has played in mediating the conflict, or look in the index for the pages where Egypt is mentioned in the text. Consider Whether Your Sources are Current Some disciplines require that you use information that is as current as possible. This is particularly true in disciplines in medicine and the sciences where research conducted becomes obsolete very quickly as new discoveries are made. However, when writing a review in the social sciences, a survey of the history of the literature may be required. In other words, a complete understanding the research problem requires you to deliberately examine how knowledge and perspectives have changed over time. Sort through other current bibliographies or literature reviews in the field to get a sense of what your discipline expects. You can also use this method to explore what is considered by scholars to be a "hot topic" and what is not.

III.  Ways to Organize Your Literature Review

Chronology of Events If your review follows the chronological method, you could write about the materials according to when they were published. This approach should only be followed if a clear path of research building on previous research can be identified and that these trends follow a clear chronological order of development. For example, a literature review that focuses on continuing research about the emergence of German economic power after the fall of the Soviet Union. By Publication Order your sources by publication chronology, then, only if the order demonstrates a more important trend. For instance, you could order a review of literature on environmental studies of brown fields if the progression revealed, for example, a change in the soil collection practices of the researchers who wrote and/or conducted the studies. Thematic [“conceptual categories”] A thematic literature review is the most common approach to summarizing prior research in the social and behavioral sciences. Thematic reviews are organized around a topic or issue, rather than the progression of time, although the progression of time may still be incorporated into a thematic review. For example, a review of the Internet’s impact on American presidential politics could focus on the development of online political satire. While the study focuses on one topic, the Internet’s impact on American presidential politics, it would still be organized chronologically reflecting technological developments in media. The difference in this example between a "chronological" and a "thematic" approach is what is emphasized the most: themes related to the role of the Internet in presidential politics. Note that more authentic thematic reviews tend to break away from chronological order. A review organized in this manner would shift between time periods within each section according to the point being made. Methodological A methodological approach focuses on the methods utilized by the researcher. For the Internet in American presidential politics project, one methodological approach would be to look at cultural differences between the portrayal of American presidents on American, British, and French websites. Or the review might focus on the fundraising impact of the Internet on a particular political party. A methodological scope will influence either the types of documents in the review or the way in which these documents are discussed.

Other Sections of Your Literature Review Once you've decided on the organizational method for your literature review, the sections you need to include in the paper should be easy to figure out because they arise from your organizational strategy. In other words, a chronological review would have subsections for each vital time period; a thematic review would have subtopics based upon factors that relate to the theme or issue. However, sometimes you may need to add additional sections that are necessary for your study, but do not fit in the organizational strategy of the body. What other sections you include in the body is up to you. However, only include what is necessary for the reader to locate your study within the larger scholarship about the research problem.

Here are examples of other sections, usually in the form of a single paragraph, you may need to include depending on the type of review you write:

  • Current Situation : Information necessary to understand the current topic or focus of the literature review.
  • Sources Used : Describes the methods and resources [e.g., databases] you used to identify the literature you reviewed.
  • History : The chronological progression of the field, the research literature, or an idea that is necessary to understand the literature review, if the body of the literature review is not already a chronology.
  • Selection Methods : Criteria you used to select (and perhaps exclude) sources in your literature review. For instance, you might explain that your review includes only peer-reviewed [i.e., scholarly] sources.
  • Standards : Description of the way in which you present your information.
  • Questions for Further Research : What questions about the field has the review sparked? How will you further your research as a result of the review?

IV.  Writing Your Literature Review

Once you've settled on how to organize your literature review, you're ready to write each section. When writing your review, keep in mind these issues.

Use Evidence A literature review section is, in this sense, just like any other academic research paper. Your interpretation of the available sources must be backed up with evidence [citations] that demonstrates that what you are saying is valid. Be Selective Select only the most important points in each source to highlight in the review. The type of information you choose to mention should relate directly to the research problem, whether it is thematic, methodological, or chronological. Related items that provide additional information, but that are not key to understanding the research problem, can be included in a list of further readings . Use Quotes Sparingly Some short quotes are appropriate if you want to emphasize a point, or if what an author stated cannot be easily paraphrased. Sometimes you may need to quote certain terminology that was coined by the author, is not common knowledge, or taken directly from the study. Do not use extensive quotes as a substitute for using your own words in reviewing the literature. Summarize and Synthesize Remember to summarize and synthesize your sources within each thematic paragraph as well as throughout the review. Recapitulate important features of a research study, but then synthesize it by rephrasing the study's significance and relating it to your own work and the work of others. Keep Your Own Voice While the literature review presents others' ideas, your voice [the writer's] should remain front and center. For example, weave references to other sources into what you are writing but maintain your own voice by starting and ending the paragraph with your own ideas and wording. Use Caution When Paraphrasing When paraphrasing a source that is not your own, be sure to represent the author's information or opinions accurately and in your own words. Even when paraphrasing an author’s work, you still must provide a citation to that work.

V.  Common Mistakes to Avoid

These are the most common mistakes made in reviewing social science research literature.

  • Sources in your literature review do not clearly relate to the research problem;
  • You do not take sufficient time to define and identify the most relevant sources to use in the literature review related to the research problem;
  • Relies exclusively on secondary analytical sources rather than including relevant primary research studies or data;
  • Uncritically accepts another researcher's findings and interpretations as valid, rather than examining critically all aspects of the research design and analysis;
  • Does not describe the search procedures that were used in identifying the literature to review;
  • Reports isolated statistical results rather than synthesizing them in chi-squared or meta-analytic methods; and,
  • Only includes research that validates assumptions and does not consider contrary findings and alternative interpretations found in the literature.

Cook, Kathleen E. and Elise Murowchick. “Do Literature Review Skills Transfer from One Course to Another?” Psychology Learning and Teaching 13 (March 2014): 3-11; Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Jesson, Jill. Doing Your Literature Review: Traditional and Systematic Techniques . London: SAGE, 2011; Literature Review Handout. Online Writing Center. Liberty University; Literature Reviews. The Writing Center. University of North Carolina; Onwuegbuzie, Anthony J. and Rebecca Frels. Seven Steps to a Comprehensive Literature Review: A Multimodal and Cultural Approach . Los Angeles, CA: SAGE, 2016; Ridley, Diana. The Literature Review: A Step-by-Step Guide for Students . 2nd ed. Los Angeles, CA: SAGE, 2012; Randolph, Justus J. “A Guide to Writing the Dissertation Literature Review." Practical Assessment, Research, and Evaluation. vol. 14, June 2009; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016; Taylor, Dena. The Literature Review: A Few Tips On Conducting It. University College Writing Centre. University of Toronto; Writing a Literature Review. Academic Skills Centre. University of Canberra.

Writing Tip

Break Out of Your Disciplinary Box!

Thinking interdisciplinarily about a research problem can be a rewarding exercise in applying new ideas, theories, or concepts to an old problem. For example, what might cultural anthropologists say about the continuing conflict in the Middle East? In what ways might geographers view the need for better distribution of social service agencies in large cities than how social workers might study the issue? You don’t want to substitute a thorough review of core research literature in your discipline for studies conducted in other fields of study. However, particularly in the social sciences, thinking about research problems from multiple vectors is a key strategy for finding new solutions to a problem or gaining a new perspective. Consult with a librarian about identifying research databases in other disciplines; almost every field of study has at least one comprehensive database devoted to indexing its research literature.

Frodeman, Robert. The Oxford Handbook of Interdisciplinarity . New York: Oxford University Press, 2010.

Another Writing Tip

Don't Just Review for Content!

While conducting a review of the literature, maximize the time you devote to writing this part of your paper by thinking broadly about what you should be looking for and evaluating. Review not just what scholars are saying, but how are they saying it. Some questions to ask:

  • How are they organizing their ideas?
  • What methods have they used to study the problem?
  • What theories have been used to explain, predict, or understand their research problem?
  • What sources have they cited to support their conclusions?
  • How have they used non-textual elements [e.g., charts, graphs, figures, etc.] to illustrate key points?

When you begin to write your literature review section, you'll be glad you dug deeper into how the research was designed and constructed because it establishes a means for developing more substantial analysis and interpretation of the research problem.

Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1 998.

Yet Another Writing Tip

When Do I Know I Can Stop Looking and Move On?

Here are several strategies you can utilize to assess whether you've thoroughly reviewed the literature:

  • Look for repeating patterns in the research findings . If the same thing is being said, just by different people, then this likely demonstrates that the research problem has hit a conceptual dead end. At this point consider: Does your study extend current research?  Does it forge a new path? Or, does is merely add more of the same thing being said?
  • Look at sources the authors cite to in their work . If you begin to see the same researchers cited again and again, then this is often an indication that no new ideas have been generated to address the research problem.
  • Search Google Scholar to identify who has subsequently cited leading scholars already identified in your literature review [see next sub-tab]. This is called citation tracking and there are a number of sources that can help you identify who has cited whom, particularly scholars from outside of your discipline. Here again, if the same authors are being cited again and again, this may indicate no new literature has been written on the topic.

Onwuegbuzie, Anthony J. and Rebecca Frels. Seven Steps to a Comprehensive Literature Review: A Multimodal and Cultural Approach . Los Angeles, CA: Sage, 2016; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016.

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Your Literature Review and Discussion Sections

3-minute read

  • 23rd November 2015

Many things go well together in this world, like fish and chips or the birds and the bees (figuratively speaking). However, one felicitous pairing that might not immediately jump to mind are the literature review and discussion sections of your dissertation.

This is because a dissertation is more than a set of discrete essays; rather, each part should be written in a way that contributes to your dissertation as a greater whole. Nowhere is this more important than in the discussion section, as it’s essential to refer to your literature review when interpreting your results.

Why? Let us explain via the ‘Three C-Words’ (no, not that one: we’re talking about context, comparison and contribution).

1.     Context!

The main purpose of your literature review is to contextualise your research by outlining previous studies conducted in the field. Referring back to the literature review in your discussion section therefore helps set the background against which your results should be interpreted, making it easier to explain their relevance to your hypothesis.

2.     Comparison!

Simply describing your results isn’t enough in the discussion section, as you also need to interpret and analyse data in terms of your research question. One way to do this is by comparing your results to those obtained in similar studies.

For example, you might want to discuss whether your results agree or disagree with those of other researchers. If there is a difference, you’ll also want to consider why this has happened and whether it’s significant.

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However, you should not introduce new research in the discussion section. Make sure that any studies you refer to in the discussion have been addressed in the literature review. And don’t be afraid to modify your literature review as your study progresses (every dissertation project will evolve as it goes on).

3.     Contribution!

As well as discussing the relevance of your results, your discussion section should usually include some reference to how your research contributes to knowledge in your field of study.

This, again, requires that you refer to your literature review, where you have discussed existing research in your field. Ideally, you will also have formulated your research questions to address a gap in the current research. Your discussion section is thus where you explain how your results fill this gap.

In summary, referring to your literature review will make sure that your discussion section is always on topic. And remember the three C-words: context, comparison and contribution.

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Thoughtful Threads: Sparking Rich Online Discussions

Thoughtful Threads: Sparking Rich Online Discussions

  • Resources & Preparation
  • Instructional Plan
  • Related Resources

Online literature circles provide students opportunities to discuss a literary work in a forum in which each student has a voice and the chance to share ideas without being interrupted by others. In this multisession lesson, students choose a novel that will spark discussion and elicit deep literature response from a list of selected titles. Students read and discuss their chosen text online with their peers and respond to both teacher- and student-created prompts. Student-constructed quality prompts invite group members to think deeper about the literature, engage in meaningful conversation, and share multiple perspectives and unique points of view. After completing an online discussion, students review a transcript of their discussions and reflect on the value of their experience.

Featured Resources

  • Reading Schedule for Online Literature Circles : Students can use this reading schedule to help guide their reading for their online literature circles. Following the reading schedule will ensure that students are always prepared for their online discussions.
  • Creating Prompts : Students can use this worksheet to help them create discussion prompts that inspire their peers to respond and comment about the literary work.

From Theory to Practice

  • Individual readers breathe life into written text through personal meaning making and prior experiences. Online literature circles have potential for fostering literacy skills as students exchange their unique perspectives and prior experiences.
  • Online literature circles support socially constructed learning as they provide students equitable opportunities to share their thoughts and voice individual opinions without being interrupted by others.
  • When students construct their own literature discussion prompts, they encourage group members to think deeper about the literature while maintaining ownership of the conversation.

Common Core Standards

This resource has been aligned to the Common Core State Standards for states in which they have been adopted. If a state does not appear in the drop-down, CCSS alignments are forthcoming.

State Standards

This lesson has been aligned to standards in the following states. If a state does not appear in the drop-down, standard alignments are not currently available for that state.

NCTE/IRA National Standards for the English Language Arts

  • 1. Students read a wide range of print and nonprint texts to build an understanding of texts, of themselves, and of the cultures of the United States and the world; to acquire new information; to respond to the needs and demands of society and the workplace; and for personal fulfillment. Among these texts are fiction and nonfiction, classic and contemporary works.
  • 3. Students apply a wide range of strategies to comprehend, interpret, evaluate, and appreciate texts. They draw on their prior experience, their interactions with other readers and writers, their knowledge of word meaning and of other texts, their word identification strategies, and their understanding of textual features (e.g., sound-letter correspondence, sentence structure, context, graphics).
  • 4. Students adjust their use of spoken, written, and visual language (e.g., conventions, style, vocabulary) to communicate effectively with a variety of audiences and for different purposes.
  • 8. Students use a variety of technological and information resources (e.g., libraries, databases, computer networks, video) to gather and synthesize information and to create and communicate knowledge.
  • 11. Students participate as knowledgeable, reflective, creative, and critical members of a variety of literacy communities.

Materials and Technology

  • Computers with Internet access
  • Classroom computer with projection capability (for demonstration)
  • Creating Prompts
  • Reading Schedule for Online Literature Circles
  • Student Progress Report
  • Transcript Group Reflection
  • Student Self-Reflection

Preparation

Student objectives.

Students will

  • Develop written communication skills as they draw on a wide range of prior experience and personal interpretation of literature and share these ideas with others
  • Formulate effective literature discussion prompts that elicit insightful conversations and encourage multiple perspectives
  • Participate as reflective members of an online literacy community by contributing to discussions and evaluating the effectiveness of such conversations

Homework: Students should complete the first reading assignment (as indicated on the Reading Schedule) prior to the next session.

Homework (due at the beginning of Session 3): Students should complete the second reading assignment. Encourage students to continue their discussion on the discussion forum.

Homework: Students should read the third section of their books (as indicated on the Reading Schedule ) prior to the next session. Encourage continued discussion on the discussion forum. Note: Prior to Session 4, review the online discussions and assess the quality of student-created prompts. (Which prompts sparked discussion? Are prompts open-ended? Do prompts invite sharing of alternative viewpoints and prior experiences?) Plan to adapt the activities in Session 4 as needed, based on the quality of students' discussions so far. Choose examples from the discussion forums to illustrate strengths and weaknesses of discussion prompts.

Homework (due at the beginning of Session 5): Students should complete the fourth reading assignment (as indicated on the Reading Schedule ). Tell students to temporarily halt their online discussion as you prepare the statistical reports for Session 5 (see note below). Note: Prior to Session 5, review the quality of students' prompts and replies. Access the statistical summary of the discussion forum (if available) and find a report showing the number and average length of each literature group's posts. Also print out an individual report for each student with information about his or her discussion forum activities, including number of posts and average length of each post (to be used in Session 5). If you are using a discussion platform (e.g., a wiki or e-mail mailing list) that does not generate statistical summaries, you will need to create comparable statistical reports. Consider copying and pasting the discussions into a Microsoft Word document and using the Word Count tool to determine the length of students' posts.

Homework (due at the beginning of Session 6): Students should read the fifth section of their books (as indicated on the Reading Schedule ) and continue communicating on the discussion board. Ask students to focus on both the length and quality of their discussions. Note: Prior to the next session print out a complete transcript of each group's online discussion and make a copy for each group member. Also create a brief example transcript (or choose an example from discussions conducted by another class) for use in Session 6.

Homework: Ask students to read the final section of their books (as indicated on the Reading Schedule ) prior to the next session and continue their online discussions. Remind students to keep their collaborative goals in mind. Note: Prior to Session 7, access the statistical summary of the discussion forum or create statistical reports as you did for Session 5 and print out individual reports for all students. (You will need to determine what kinds of reports are available to you and decide how to best use the information. For example, you may wish to include data from the beginning of the project, or only data for the time since the previous analysis in Session 5.)

  • Encourage the literature circle groups to visit websites relating to their book and its author. Authors' websites are listed on the Suggested Books handout. If you are using alternative titles, The Reading Zone at the Internet Public Library may serve as a springboard to many authors' websites.
  • Have each group prepare and present a book talk or book review about their book, to encourage other students to read it as well.
  • Next time students participate in face-to-face book clubs or literature circles, invite them to create their own prompts to spark discussion

Student Assessment / Reflections

  • Review students’ posts on the discussion board prior to each session. Notice the quality and length of each post. Address any concerns or misconceptions at the beginning of each session. Note: It is important to recognize that length does not always correspond with quality. The statistical summaries should not be used alone to evaluate students’ performance.
  • Before students post their first prompts at the end of Session 3, review each student’s Creating Prompts handout to check for quality and understanding. Continue to monitor the discussion forum to ensure high quality of prompts.
  • At the end of Session 5, collect the completed Student Progress Reports . Assess each student’s progress and discussion forum contributions in comparison to the group’s average. Meet with students individually to discuss their goals and support them in achieving those goals.
  • At the end of Session 6, collect the completed Transcript Group Reflections . Use students’ observations on the handout to make sure students understand how different kinds of prompts affect subsequent conversations. Discuss each group’s goals with the group members and support the groups in achieving those goals.
  • At the end of Session 7, collect the Student Self Reflection from each student. Review individual goals from Session 5 and note progress in achieving these goals. Offer feedback to individual students.
  • Lesson Plans
  • Strategy Guides
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  • Kindergarten K
  • Open access
  • Published: 04 October 2023

A scoping review of the barriers and facilitators to accessing and utilising mental health services across regional, rural, and remote Australia

  • Bianca E. Kavanagh   ORCID: orcid.org/0000-0002-1656-2775 1 ,
  • Kayla B. Corney 2 ,
  • Hannah Beks   ORCID: orcid.org/0000-0002-2851-6450 1 ,
  • Lana J. Williams   ORCID: orcid.org/0000-0002-1377-1272 2 ,
  • Shae E. Quirk 2 , 3 , 4 &
  • Vincent L. Versace   ORCID: orcid.org/0000-0002-8514-1763 1  

BMC Health Services Research volume  23 , Article number:  1060 ( 2023 ) Cite this article

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Inadequate healthcare access and utilisation are implicated in the mental health burden experienced by those living in regional, rural, and remote Australia. Facilitators that better enable access and utilisation are also reported in the literature. To date, a synthesis on both the barriers and facilitators to accessing and utilising mental health services within the rural Australian context has not been undertaken. This scoping review aims to (1) synthesise the barriers and facilitators to accessing and utilising mental health services in regional, rural, and remote Australia, as identified using the Modified Monash Model; and (2) better understand the relationship between barriers and facilitators and their geographical context.

A systematic search of Medline Complete, EMBASE, PsycINFO, Scopus, and CINAHL was undertaken to identify peer-reviewed literature. Grey literature was collated from relevant websites. Study characteristics, including barriers and facilitators, and location were extracted. A descriptive synthesis of results was conducted.

Fifty-three articles were included in this scoping review. Prominent barriers to access and utilisation included: limited resources; system complexity and navigation; attitudinal and social matters; technological limitations; distance to services; insufficient culturally-sensitive practice; and lack of awareness. Facilitators included person-centred and collaborative care; technological facilitation; environment and ease of access; community supports; mental health literacy and culturally-sensitive practice. The variability of the included studies precluded the geographical analysis from being completed.

Both healthcare providers and service users considered a number of barriers and facilitators to mental health service access and utilisation in the regional, rural, and remote Australian context. Barriers and facilitators should be considered when re-designing services, particularly in light of the findings and recommendations from the Royal Commission into Victoria’s Mental Health System, which may be relevant to other areas of Australia. Additional research generated from rural Australia is needed to better understand the geographical context in which specific barriers and facilitators occur.

Peer Review reports

Introduction

The mental health of Australians who live in regional, rural, and remote Australia is an ongoing concern [ 1 ]. Poor healthcare access is one of the key determinants of adverse mental health outcomes, with access issues being more pronounced in regional, rural, and remote Australia (hereafter referred to as rural , in line with the Australian Government’s definition under the Rural Health Multidisciplinary Training [RHMT] Program [ 2 ]), compared to metropolitan Australia [ 3 ]. People living in rural Australia often face difficulties in obtaining healthcare, and this care is often delayed and more expensive for the patient [ 4 ]. These difficulties in accessing and utilising healthcare are implicated in the higher mental disorder burden experienced by those living in rural Australia, shown by the higher rates of suicide, compared with major cities [ 5 ]. Moreover, this group is less likely than those living in major cities to take-up and complete mental health treatment [ 6 ]. Workforce maldistribution plays a role in these health inequalities [ 7 , 8 , 9 , 10 ], with more clinical full time equivalent (FTE) mental health professionals working in major cities, compared with rural areas (i.e., 92 vs. 30–80 mental health nurses, 15 vs. 2–6 psychiatrists, and 90 vs. 15–55 psychologists per 100,000/population) [ 3 ]. Other areas of the health workforce are similarly maldistributed across the country (i.e., 403 vs. 223–309 clinical FTE medical practitioners and 531 vs. 382–469 clinical FTE allied health professionals per 100,000/population in major cities versus rural areas) [ 11 ].

There are a number of factors that are implicated — both directly and indirectly — in the access and utilisation of mental health services, and these factors may be pertinent to the level of remoteness experienced. This includes particular aspatial (i.e., social) and spatial (i.e., geographical) dimensions [ 12 , 13 ]. Aspatial dimensions consist of the factors that affect the affordability , acceptability , accommodation , and awareness of healthcare access. In the rural context of Australia, this tends to relate to social matters [ 14 , 15 ] including stoicism, low help-seeking behaviours, and confidentiality concerns [ 16 ]. Spatial dimensions are concerned with the availability and accessibility of service access, including geographical isolation [ 14 ], service delivery capacity [ 17 ] [ 18 ], and dual-roles [ 14 ] (i.e., the intersection of professional and personal relationships) in rural areas. While here we define access as factors that pertain to the attributes/expectations of the individual and their alignment with the provider/services [ 12 ], other models conceptualise access as the opportunity to identify healthcare needs, seek services, reach resources, obtain or use services, and have the need for services fulfilled [ 19 ]. Utilisation refers to the generation of a healthcare plan throughout a healthcare encounter, as well as its implementation and follow-through [ 20 ].

Conceivably, mitigating the barriers and augmenting the facilitators to the utilisation of mental health services may be particularly important when considering the obstacles that people from rural areas face when accessing services. One previous study on rurally-based Australian adolescents suggested that barriers to accessing services, such as social exclusion and ostracism by members of their community, also likely prevented the continued utilisation of services and negatively affected treatment outcomes [ 21 ]. Cheesmond et al. [ 22 ], in a review of residents in rural Australia, Canada, and the United States of America, highlighted a link between sociocultural rurality, rural identity, and help-seeking behaviour. Cheesmond et al. [ 22 ] suggested that specific place-sensitive approaches are needed to overcome barriers to help-seeking, and that a greater understanding of help-seeking in the rural context is required. This includes further exploration of rurality as a concept, conducting research within diverse environments, allowing participants to contextualise barriers to help-seeking, and exploring the co-existence of multiple help-seeking barriers. Parallel to this, a paucity of research has focussed on the facilitators to accessing and utilising mental health services in rural Australia.

To the authors’ knowledge, no previous reviews have specifically focussed on understanding the barriers and facilitators to accessing and utilising mental health services within the rural Australian context. A scoping review was chosen as the preferred approach to this work because of the emerging and cross-disciplined nature of the research. The aim of this scoping review is to: (1) explore the barriers and facilitators to accessing and utilising mental health services for Australians living in rural areas; and (2) better understand the relationship between barriers and facilitators and their geographical context.

This scoping review conforms to the guidelines put forward by Arksey and O’Malley [ 23 ], follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRISMA-ScR) [ 24 ], and a published protocol [ 25 ].

Eligibility criteria

The scope of this review was intentionally broad to allow explanation of the nature and extent of the literature describing the barriers and facilitators to accessing and utilising mental health services across regional, rural, and remote Australia. Articles were eligible for inclusion if they met the following criteria:

Included individuals with a diagnosed mental disorder, experienced mental health issues, or were part of a mental health community service; or included healthcare providers that provided diagnostic, assessment, or treatment services for mental health issues.

Explained obstacles that impeded the uptake, quality, or level of mental health services being accessed or described facilitators that allowed the uptake, quality, or level of mental health services being received.

Included service users, healthcare providers, or services that were based in regional, rural, or remote Australia according to the Modified Monash Model (MMM) 2–7 ( regional centres to very remote communities ) [ 4 ] (i.e. the current RHMT definition of rural).

The population/concept/context (PCC) framework was used to generate the eligibility criteria for this scoping review and is described in Table  1 . The eligibility criteria for this review varied slightly from the published protocol [ 25 ]. In this review, we included pharmacists as healthcare providers, as it was identified that pharmacists play a key role in mental health services in some rural areas. We excluded mental health programs and health promotion activities that were considered to be a “structured activity” delivered by a service, reviews, viewpoints, declarations, tailpieces, frameworks, and commentaries. We also excluded articles that did not provide sufficient detail to describe the barriers or facilitators to accessing or utilising services, as well as articles that pooled results across participants from metropolitan and regional/rural/remote areas. The only exception to this was when authors referred to the study setting as regional/rural/remote, but upon further investigation using the health workforce locator [ 26 ] (see Sect.  2.8 Geographical analysis ), the location was deemed to be metropolitan according to the MMM [ 4 ] — this exception was allowed due to the differences in geographical models applied to Australian health research [ 27 , 28 ]. Separately, we decided to include articles that reported on the barriers and/or facilitators of a specific rural mental health service implementation activity or service model, as we felt that these articles offered important insights that may be translated to new service initiatives or research activities.

Information sources

The following databases were systematically searched: Medline Complete, EMBASE, PsycINFO, Scopus, and Cumulative Index of Nursing and Allied Health Literature (CINAHL). Websites of the Australian federal and state government’s Department of Health, Primary Health Network (PHN), key rural and remote peak bodies/agencies known to the authors from their collective experience on the topic, and Google were also searched to ascertain grey literature. The search was performed on 11th January 2022 and a 2012-current date filter was employed using the ‘start’ and ‘end’ publication year functions. Additional sources were identified through ‘snowball’ searching of included studies. Where needed, additional location information was obtained via a study’s first or corresponding author.

The search strategy was developed in consultation with two scholarly services librarians (JS and BK) to identify peer-reviewed studies and grey literature records. Relevant keywords, search terms, and wildcard symbols were applied to each database. An adapted search string was searched in Google using the advanced search function. The “all these words” and “any of these words” search options were engaged, and PDF files were requested. All (n = 11) pages of the search results were assessed for eligibility by one reviewer (BEK), and the research term agreed on their inclusion.

The full search strategy and grey literature sources are presented in Additional Table  1 .

Selection of sources of evidence

One reviewer (BEK) applied the search strategy to the databases and websites. Two reviewers (BEK and KBC) independently screened all articles using Covidence [ 29 ]. Where discrepancies concerning the eligibility of an article occurred, a meeting was held to determine consensus; if consensus could not be reached, a third reviewer (LJW) was consulted to make the final decision.

Data charting process

To ensure that the data charting process was consistent with the research question, a charting form was developed and piloted by two authors (BEK and KBC). One author (BEK) then charted the data for each of the eligible articles, using Microsoft Excel.

The following data items were extracted from eligible studies: author and year, study objective, study design, location, sample size, characteristics of participants, mental health diagnosis/issue and assessment method, healthcare provider type/role, barriers, facilitators, mental health service, regional/rural/remote area of Australia, and summary of findings (Additional Table  2 ). For literature that included participants from both metropolitan and regional/rural/remote areas, only information that pertained to those from regional/rural/remote areas was extracted, except for instances where statistical differences between groups were reported for comparison. Likewise, in instances where articles included participants who were eligible (e.g., healthcare providers) as well as participants who were ineligible (e.g., no evidence of mental health diagnosis/engagement with services), only information from eligible participants was extracted. First or corresponding authors of studies that did not specifically state where the study was conducted were contacted to provide additional location information.

Synthesis of results

A descriptive synthesis was conducted by providing an overview of the included study characteristics, setting and target groups, and barries and facilitators. Links to aspatial and spatial access factors were also described, where relevant. The study characteristics are presented in Table  2 and the barriers and facilitators pertaining to each included study are presented in Additional Table  3 . A quality appraisal of the included studies was not undertaken as scoping reviews aim to offer an overview or map of the pertinent evidence [ 30 ].

Geographical analysis

Geographical coordinates provided by the health workforce locator [ 26 ] were used to determine the remoteness of the study locations according to the MMM categories. These data were inputted into STATA to determine the number and proportion of each of the MMM categories.

The database search yielded 1,278 articles, of which 555 articles were removed due to duplication. Subsequently, 723 titles and abstracts were screened, and 441 were excluded due to ineligibility. At the full text stage, 282 articles were screened, with 181 studies being excluded, resulting in 47 articles meeting the eligibility criteria. The grey literature search yielded 128 potentially relevant sources, of which six were eligible after removing three for duplication. In total, 53 articles were included in this scoping review. A snowball search of the references of included records was also conducted and two additional records were identified but were deemed ineligible as they reported on studies/samples that were already included in the review. Figure  1 displays the PRISMA flow throughout each screening stage.

figure 1

PRISMA flow diagram of studies considered in this review

Study characteristics

Of the 53 included studies, 25 articles described barriers and/or facilitators from the healthcare provider perspective, 13 were from the point of view of the service user, eight reported on combined perspectives of both the healthcare provider and service user, and seven reported on barriers/facilitators from neither the healthcare provider nor service user perspective directly but did consider the barriers/facilitators of the service environment (e.g., service evaluations).

Most studies (n = 29, 54.7%) employed qualitative methods, including interviews and/or focus groups; 12 studies utilised quantitative cross-sectional or longitudinal methods, seven were mixed-methods research designs, and two were service description and classification studies.

The highest proportion of studies were conducted in New South Wales (NSW) (n = 13) [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ], followed by Australia broadly (n = 12) [ 33 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ], South Australia (SA) (n = 10) [ 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ], Victoria (VIC) (n = 6) [ 65 , 66 , 67 , 68 , 69 , 70 ], Queensland (QLD) (n = 5) [ 71 , 72 , 73 , 74 , 75 ], Western Australia (WA) (n = 3) [ 76 , 77 , 78 ], Tasmania (TAS) (n = 2) [ 79 , 80 ], and Northern Territory (NT) (n = 1) [ 81 ]. One study pertained to areas within NSW, QLD, and VIC [ 82 ], and another study concerned NSW and WA [ 83 ]. No studies were centred on Australian Capital Territory (ACT). Table  2 depicts the characteristics of the included studies.

Setting and target groups

Mental health service setting.

Fourteen studies reported on general or community-based mental health services [ 18 , 33 , 43 , 48 , 53 , 54 , 57 , 64 , 72 , 74 , 77 , 78 , 83 ]. Four studies described mental health services provided within emergency departments (EDs) and/or urgent care centres (UCCs) [ 40 , 41 , 46 , 65 ]. The remaining studies described mental health services provided by counsellors and GPs [ 38 ], nurses, peer-workers [ 71 ], personal helpers and mentors [ 35 ], pharmacists [ 47 ], and a combination of several healthcare providers [ 59 ]. Seven studies reported on technology-based or -enhanced mental health services [ 51 , 60 , 61 , 62 , 63 , 75 , 76 ].

Target groups

The population group focus of studies varied. Of the studies that commented on, or specified that they targeted specific subpopulations, four studies discussed care pertinent to Indigenous or Aboriginal and/or Torres Strait Islander Peoples [ 66 , 67 , 68 , 81 ]. Four studies discussed mental health services for young people [ 55 , 63 , 73 , 82 ]. Three studies specifically included at least a proportion of service users who were under the age of 18 years old [ 55 , 61 , 79 ]. Two studies reported on mental health services for older people [ 50 , 58 ]. Other studies described barriers and or facilitators specific to sex workers [ 80 ], medical doctors [ 45 ], LGBTIQA + people [ 51 ], immigrants [ 49 ], and women [ 39 ] or men [ 70 ] with specific mental health issues. Three studies described mental health services that were specific for supporting people with depression [ 34 , 39 , 55 ]; two studies were focussed on suicide [ 68 , 70 ]; two studies described care for people with eating disorders [ 42 , 52 ]; and one study was centred on perinatal and infant support [ 75 ].

Barriers and facilitators

The included studies varied significantly. This included differences in the purpose and type of study, participant sample, and methodology, and reporting of findings. Barriers and facilitators were grouped into prominent concepts based on terminology used by the relevant literature and are presented in Table  3 . Barriers related to limited resources; system complexity and navigation; attitudinal and social matters; technological limitations; distance to services; insufficient culturally-sensitive practice; and lack of awareness. Facilitators related to person-centred and collaborative care; technological facilitation; environment and ease of access; community supports; mental health literacy; and culturally-sensitive practice.

Prominent barrier concepts

Barriers affecting healthcare providers and service users.

Limited resources. Across the studies, the most considerable barrier was limited resources [ 18 , 33 , 34 , 35 , 36 , 38 , 39 , 42 , 45 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 71 , 74 , 75 , 78 , 79 , 80 , 82 ]. This key concept considered limited resources at the healthcare provider and service user level. Notably, lack of available general and specialist services, limited service capacity, workforce shortages, difficulty attracting and retaining staff, and staff turnover were frequently reported as considerable spatial barriers to service delivery, hampering access to services. Moreover, financial costs, disadvantage, or appointment fees [ 34 , 37 , 52 , 53 , 61 , 62 , 78 ], and lack of transport [ 34 , 50 , 52 , 53 , 58 , 62 , 71 , 78 ] restricted access to mental health services for the service user. These issues reflect the lower relative socio-economic advantage seen in rural areas of Australia [ 2 ].

System complexity and navigation. The complexity in using and navigating the system was a common aspatial barrier [ 18 , 33 , 36 , 40 , 41 , 42 , 45 , 46 , 51 , 52 , 53 , 57 , 58 , 59 , 61 , 63 , 65 , 66 , 69 , 73 , 74 , 78 , 80 ], which affected healthcare providers in coordinating patient care and service users in utilising such care. These issues were most frequently reflected in reports on extended wait times and delays in assessment and diagnosis [ 34 , 40 , 46 , 53 , 55 , 57 , 58 , 62 , 66 , 78 , 80 ].

Attitudinal or social matters. Many studies reported that attitudinal or social matters were a barrier for the service user [ 34 , 35 , 36 , 38 , 39 , 43 , 50 , 51 , 52 , 60 , 61 , 64 , 66 , 67 , 68 , 70 , 78 , 80 , 81 ], particularily concerning privacy or confidentiality concerns [ 39 , 51 , 60 , 61 , 62 , 63 , 66 , 67 , 78 ], affecting aspatial access to care. The need to be stoic was reported as a barrier to seeking psychological help among regional medical doctors, relating to their perceptions of regional practitioner identity [ 45 ], and among service users [ 50 , 67 , 70 ].

Technological limitations. Several studies cited limitations to services delivered via technological means [ 51 , 53 , 60 , 61 , 62 , 64 , 78 ]. Some studies acknowledged that technology can enhance physical mental health services, but cannot replace them [ 62 , 64 ], particularly for specific client groups, including the older population and Aboriginal and Torres Strait Islander people, who reportedly prefer face-to-face service delivery [ 78 ]. In addition, poor connectivity and high costs of technology use were reported as aspatial barriers to accessing technology-delivered mental health services and may also affect their utilisation [ 53 , 62 , 78 ].

Lack of awareness. Lack of awareness about mental health issues, needs, or services available was reported as an aspatial barrier in the current review [ 43 , 50 , 52 , 67 , 78 ]. This lack of awareness was reported at the healthcare provider level in one study, and was described as the healthcare provider having a limited understanding of the mental health needs in older people, resulting in a lack of referral to appropriate services [ 50 ]. At the service user level, a lack of awareness precluded individuals from recognising mental health problems [ 67 ], while a lack of awareness of services was a barrier to seeking help [ 52 , 78 ].

Barriers affecting service users

Distance to services. The spatial distance required to travel to physical services is a considerable issue for people residing in rural localities, and this distance has been shown to reduce service access and utilisation in the current review [ 52 , 62 , 63 , 64 , 67 , 71 , 78 ]. There is also an additional burden experienced by those with physical disability, or those who don’t have a support person to assist them [ 53 ].

Insufficient culturally-sensitive practice. A limited capacity to meet the needs of culturally and linguistically diverse (CALD) and Aboriginal and Torres Strait Islander communities was reported, affecting aspatial access and utilisation of services. This tended to be a result of service users not feeling culturally safe within the service environment, perceptions that health professionals had cultural assumptions about the service user, and inappropriate assessment tools [ 48 , 49 , 58 , 73 , 78 ].

Prominent facilitator concepts

Facilitators affecting healthcare providers and service users .

Person-centred and collaborative care. Many studies reported that person- (or client-) centred care that is non-judgemental and permits collaboration to be an important aspatial facilitator to mental health service access and utilisation [ 31 , 34 , 35 , 36 , 41 , 42 , 56 , 57 , 58 , 59 , 61 , 63 , 64 , 65 , 72 , 74 , 81 ]. It is noteworthy that person centred care was specifically reported in studies pertaining to the service user [ 61 ] and healthcare provider [ 63 , 64 ] in the current review, suggesting that this approach is recognised as important by both those delivering and using the service. Care that is regular and non-intrusive was seen as a way to facilitate service utilisation [ 34 , 57 ].

Technological facilitation. Technology-based services, including integrated mental health services, telehealth, live chat, SMS appointment reminders and coordination, and mental health web-pages, were reported to be useful in filling spatial and aspatial gaps in service delivery for physical services [ 51 , 53 , 58 , 60 , 61 , 62 , 63 , 75 , 76 , 78 ]. These services were reported to facilitate connection and information sharing [ 62 ], clinical supervision, contact with specialists [ 60 ], workforce upskilling, and security [ 75 ] for the healthcare provider. For the service user, technology-based services facilitated immediacy of consultations, cost savings, and anonymity, and reduced mental health hospitalisations and admissions, additional client appointments, the need to travel, stigma, and family stress [ 60 ].

Environment and ease of access. The mental health service environment and the ease of which one may access services — granted that all other access issues are overcome — were frequently reported as spatial facilitators [ 31 , 49 , 65 , 73 , 80 , 81 ]. Specifically, services that permitted a non-clinical and comfortable environment were deemed as important aspatial factors for young people [ 61 , 73 ]. Co-located services were also considered important for access, as this allows service integration and facilitated information sharing [ 31 , 41 , 63 ].

Community supports. The community was considered to be an important aspatial facilitator. This included healthcare providers being involved and connected with the community [ 56 , 65 , 66 ], as well as having a sense of community [ 59 ], as a way to facilitate care via information sharing, collaboration, and knowing community members and local issues. For the service user, community and place was seen as a source of strength as noted by one study [ 39 ].

Facilitators affecting service users

Mental health literacy. Several studies reported that having awareness of mental health issues and being confident in using services were aspatial facilitators to mental health service access and utilisation [ 52 , 57 , 59 , 66 , 70 ]. These factors are generally referred to as mental health literacy within the wider literature, which is a crucial component of healthcare [ 84 ].

Culturally-sensitive practice. Of the studies that reported on cultural elements of mental health service provision, it was noted that Indigenous and other culturally appropriate staff (i.e., a Koori Mental Health Liaison Officer or Aboriginal Mental Health Worker), as well as the involvement of Community Elders and spiritual healers [ 48 ] assisted with service access and utilisation [ 48 , 66 ]. Further, culturally appropriate décor and flexibility in meeting places [ 66 ], and the use of culturally acceptable models of mental health [ 48 ] were also seen as important aspatial dimensions.

Overall, thirty studies were described as being relevant to rural areas [ 18 , 31 , 33 , 34 , 35 , 36 , 38 , 39 , 42 , 43 , 48 , 49 , 50 , 53 , 57 , 58 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 73 , 76 , 78 , 83 ], three studies were pertinent to regional areas [ 39 , 56 , 79 ], two studies were concerned with remote areas [ 77 , 81 ], and the remaining studies involved combinations of regional/rural/remote populations of Australia [ 37 , 40 , 41 , 44 , 45 , 46 , 47 , 51 , 52 , 54 , 55 , 59 , 60 , 71 , 74 , 75 , 80 , 82 ]. Over one third of the studies (n = 21, 39.6%) reported or provided specific spatial data, which allowed the MMM [ 4 ] to be applied directly to the study location; n = 10 (47.6%) of these studies included multiple locations, resulting in a total of 41 MMM categories. Studies were conducted most frequently in MM5 small rural towns (n = 10, 24.4%) and MM3 large rural towns (n = 9, 22.0%) and least frequently in MM6 remote communities (n = 3, 7.3%). The first author’s location was used as a proxy location for 28 studies (52.8%). Of these studies, the most frequent location was MM1 metropolitan settings (n = 16, 57.1%), likely due to the high proportion of study locations being taken from the first author’s location, and that many universities and research centres are located in major cities. There were no studies conducted in MM5 small rural towns (n = 0, 0%). Three author locations (5.7%) could not be determined due to limited information provided. Table  4 displays details of the MMM categories according to spatial data reported or obtained and proxy locations. Due to the heterogeneity and lack of mutual exclusivity of the data, an analysis of the association between geographical area and specific barriers and facilitators was unable to be completed.

Discussion and implications

This scoping review identified the barriers and facilitators experienced by healthcare providers delivering mental health services and individuals accessing, or attempting to access mental health services in rural Australia. Prominent barriers included: limited resources; system complexity and navigation; attitudinal and social matters; technological limitations; distance to services; insufficient culturally-sensitive practice; and lack of awareness. Facilitators included person-centred and collaborative care; technological facilitation; environment and ease of access; community supports; mental health literacy and culturally-sensitive practice. We also aimed to understand these barriers and facilitators in relation to their geographical context; however, the variability in the data precluded the geographical analysis from being completed.

This study revealed a paucity of research conducted in MM6 remote and MM7 very remote communities in Australia when specific spatial data are considered, as well as in the ACT — however, it is noted that the majority of the ACT is classified as metropolitan, with 99.83% (387,887 residents) of the population residing in MM1 at the time of the 2016 census [ 2 ]. Moreover, when proxy study locations are used, many studies are conducted by researchers located in metropolitan areas. Only three studies specifically included service users who were under the age of 18 years old, representing a significant gap in understanding the mental health service needs of the younger population. Although it is acknowledged that there are considerable research ethics restrictions in place to protect children and young people, the onset of many mental health issues tends to occur between 14.5 and 18 years of age [ 85 ], highlighting the importance of understanding barriers and facilitators to accessing mental health services amongst the younger cohort. Due to the heterogeneity of the findings, the following discussion considers the most prominent barriers and facilitator concepts identified across the studies.

Review findings support limited resources as being one of the biggest restrictors of mental health service access and utilisation within rural Australia. Thes findings echo reports at the national scale, which show the mental health workforce is heavily concentrated in metropolitan areas compared to other remoteness areas, relative to the population [ 86 ]. Considerable efforts need to be made to reduce the resource inequalities, including the dearth of mental health professionals practicing outside of metropolitan cities. Recently, the National Mental Health Workforce Strategy Taskforce (the Strategy) was established to deliberate the quality, supply, distribution, structure, and methods to improve attracting, training, and retaining Australia’s mental health workforce [ 87 ]. The Consultation Draft of the Strategy highlights six objectives, including (1) careers in mental health are recognised as, attractive; (2) data underpins workforce planning; (3) the entire mental health workforce is utilised; (4) the mental health workforce is appropriately skilled; (5) the mental health workforce is retained in the sector; and (6) the mental health workforce is distributed to deliver support and treatment when and where consumers need it [ 88 ]. These objectives reflect the systemic resource issues cited in the current scoping review and emphasise the importance of a contemporary approach to increasing resources for mental health services in rural Australia. This contemporary approach is important, as it has previously been acknowledged that increasing graduates has not resolved workforce maldistribution in other areas of healthcare (i.e., medical physicians), but rather, an improved distribution of both human and other resources is needed [ 89 , 90 ].

For the service user, resource issues spanned both aspatial and spatial dimensions and include the affordability (i.e., perceived worth relative to cost) and accessibility of the service (i.e., the location of the service and ease of getting to that location) [ 12 , 13 ]. Transport issues were commonly reported to be a resource issue within the current review and the wider literature. Limited transport compounds access issues for specific subpopulations, such the elderly, particularly when they do not have personal transport and when there is no public transport available [ 50 ]. This issue is likely compounded by resource limitations, including the cost of travel, and is specifically related to spatial distance to services. Distance to services is a significant barrier to accessing healthcare. Wood et al. [ 91 ] in a systematic review, identified that there is a lack of research which measures spatial access specific to mental health services in Australia, and highlighted a need for consensus on what is reasonable access to healthcare services. Further, reports have noted that while distance alone is a significant barrier to accessing healthcare, accommodation may sometimes need to be sought depending on the time of the appointment, adding to the cost of attending the appointment [ 92 ] and further perpetuating the resource issues experienced by those living in rural areas of Australia. In addition, although not specifically reported in the current review, it is likely that the time required for traveling to and attending such appointments may require the individual to choose between tending to work or family needs or receiving the help needed.

Transport and other resource issues, as well as distance to services, may be mitigated through telehealth appointments, which have been central to the provision of healthcare since the beginning of the COVID-19 pandemic. However, the utilisation of telehealth requires many patients to have had a face-to-face consultation with their GP in the previous 12 months [ 93 ], which may preclude some Australians from rural areas from its use, considering the significant workforce maldistribution previously discussed. Moreover, rural areas of Australia also experience digital disadvantage as a result of lower internet connectivity — brought about by the high costs of installing internet infrastructure in rural and remote areas — and the socio-economic disadvantage experienced by those who live outside of metropolitan areas [ 94 ]. These issues are compounded by an ageing population, lower educational levels, a larger primary industry sector, a higher unemployment rate, and a higher Indigenous population in rural and remote Australia [ 94 ]. High cost, connectivity issues, and suitability for specific client groups should be key considerations in the delivery of technology-based mental health services. Notwithstanding these issues, the current review identified that technology-based services may be a useful adjunct to physical services, particularly in relation to reducing the need to travel, consultation immediacy, and clinician upskilling. This finding partially supports a recent systematic review, which found that youth located in rural and remote areas of Australia and Canada prefer to see mental health professionals in person, with telehealth provided as an additional option [ 95 ]. As such, the benefits and limitations to technology-based mental health services needs to be carefully considered by those designing services.

A key barrier to both access and utilisation in the current review was the complexity of using and navigating the mental health system. These issues typically occur at the system and organisation level and affect the way a service operates and its culture, making it challenging for service users to receive effective care. A complex mental health system and service fragmentation has been previously reported to lead to confusion and a lengthy amount time spent trying to navigate the system, with these issues being even greater amongst those who are younger, less autonomous, or who have less experience navigating the system [ 96 ]. System navigation initiatives may address this gap and have previously been implemented via the Partners in Recovery (PIR) program — established to facilitate care coordination for people with severe and persistent mental illness — with positive impacts for those who used the program [ 97 ]. However, the introduction of the National Disability Insurance Scheme has superseded the PIR program, and has rendered many former PIR program participants ineligible for support [ 98 , 99 ], representing a significant gap in mental health service navigation and care coordination support. Isaacs et al. [ 100 ], identified that it is more cost effective to support people with severe and persistent mental illness to access PIR supports than to not provide this support, due to the potential increased need for other services (e.g., hospital admissions, homelessness supports, residential supports). Indeed, the Australian Government’s Productivity Commission (Productivity Commission) recommended that life insurers should have greater flexibility to fund approved mental health services to reduce the likelihood of hospitalisation for mental health issues [ 101 ]. In addition, Isaacs et al. [ 100 ] reported that co-located services — which were reported as a facilitator in the current review — and the increased need of non-clinical support through mental health community support services, offered via non-governmental and not-for-profit organisations, were demonstrated to be important considerations for cost effective mental health care.

Attitudinal or social matters are frequently reported to be key barriers for rural Australians to accessing care and are considered to be an aspatial dimension [ 12 , 13 ]. These matters which include stigma, fear of judgement, stoicism, lack of trust, preference for keeping to oneself, and reluctance to seek help have been reported on the global scale as impacting upon help-seeking in rural areas in relation to rural identity [ 22 ]. Stoicism, in particular, is ordinarily viewed as a positive trait, with rural participants of a global review contextualising stoicism as an inflexible element to their core identity, however, this trait has repeatedly been reported as a barrier to the uptake of mental health services in this review [ 45 , 50 , 67 , 70 ] and in the wider literature [ 22 ]. In terms of addressing attitudinal and social matters, previous Australian research [ 16 ] has identified that intentions to seek help for a mental or emotional issue decreased with a higher classification of remoteness. Moreover, stoicism and attitudes towards seeking professional help were predictive of help-seeking intentions for participants from both rural and metropolitan areas, but sex, suicidality, and previous engagement with a mental health professional were additionally predictive of help-seeking intentions for rural Australians [ 16 ]. The current scoping review identified few studies that specifically reported on these issues in relation to barriers to accessing services [ 37 , 55 , 68 , 70 ], suggesting a need to increase research focus on these issues. Interestingly, Kaukiainen and Kõlves [ 16 ] study, found that attitudes towards seeking professional help mediated the relationship between stoicism and help-seeking intentions for participants from both rural and metropolitan locations, suggesting that attitudes towards seeking professional help may be a fruitful avenue to target to increase help-seeking intentions for all Australians [ 16 ]. Education programs delivered in secondary school or tertiary settings have been suggested as a way to improve attitudes towards help-seeking and stigma [ 102 ]. These avenues may also be useful to increase mental health literacy (i.e., the public knowledge and recognition of mental disorders and knowing where and how to seek help) [ 84 ] in the community, given that lack of awareness was a barrier and mental health literacy was a facilitator in the current review.

Providing person-centred and collaborative care was reported as a key facilitator in the current review. Person-centred care is generally defined as care that is holistic and incorporates the person’s context, individual expression, beliefs, and preferences, and includes families and caregivers, as well as prevention and promotion activities [ 103 ]. Indeed, person-centred care is a prominent practice model in mental health care, and this model of care may be particularly beneficial in rural Australia, given that it aims to decrease barriers between health service providers via shared knowledge. This model of care is collaborative by nature, although it should be noted that collaborative care is a distinct, though related model of care. Collaborative care refers to health professionals and patients working together to overcome a mental health problem [ 104 ]. This model of care has been shown to improve depression and anxiety outcomes across the short to long term (i.e., 0–24 months), and has benefits on medication use, patient satisfaction, and mental health quality of life [ 104 ]. The Productivity Commission recommended the trial of innovation funds to diffuse best practice in mental health service delivery and to eliminate practices that are no longer supported by evidence [ 101 ]. Such innovation funds may allow healthcare providers to maintain currency on practices such as person-centred and collaborative care. Importantly, the Royal Commission into Victoria’s Mental Health System (the Royal Commission) [ 90 ] identified person-centred care as a way to promote inclusion and prevent inequalities, and was specifically linked to providing culturally safe mental health care — which was noted as a facilitator to access and utilisation in the current review and has been highlighted as an important approach to eliminate health inequalities [ 105 ]. Moreover, the Royal Commission recommended the use of an integrated service approach — where service providers can work together to provide care [ 90 ]. This approach to care may mitigate service fragmentation and system complexity and navigation barriers, and also permit environments that are comfortable and allow ease of use — as identified as facilitators in the current review.

Community support, both in the sense of individuals feeling connected to the community and healthcare providers being seen within the community, was a key concept in the current review. For the service user, Johnson et al. [ 39 ] reported that accessing services under the scrutiny of the community was seen as a challenge, but that the community was also seen a source of strength. Crotty et al. [ 56 ] noted the duality for healthcare providers being involved with the community in both a social and professional sense, leading to both challenges and a feeling of togetherness. This sense of togetherness reflects the historical view that rural and remote communities have been connected over several generations [ 106 ]. Notably, in the current review, one study on healthcare provider perspectives on workforce retention reported that personal connections and a ‘natural’ connection to the community were key factors in the decision for staff working in remote areas to stay [ 33 ], suggesting the importance of embedded relationships in this setting. Preferences to stay in rural and remote towns have been associated with a sense of belonging and the quality of diverse and interesting activities, particularly for younger people [ 107 ], and these factors should be strengthened to permit the retention of the rural mental health workforce.

It is noteworthy that many of the studies were undertaken at metropolitan locations, suggesting that much of the research completed on rural locations was not necessarily conducted within this setting. However, it is acknowledged that many university locations are affiliated with major campuses, which are often located in metropolitan areas. Simultaneously, many rurally-based health and community services do not have the resources to undertake locally-generated research, and this consequently limits the evidence available for policymakers to make informed decisions regarding the health of the rural population — noting that place-based approaches are gaining traction [ 108 , 109 , 110 ]. This area is a key focus of the RHMT program [ 111 ]. The RHMT program aims to maximise investment in of Australia via academic networks, developing an evidence-base, and providing training in rural areas for health professionals. To date the RHMT program has seen that health graduates who undertook clinical placements in the most rural settings are working more in rural locations [ 112 ], and this is likely to have flow-on effects for healthcare providers to build connections to these areas, retain the workforce, and increase health outcomes for the community.

This review highlights the need for a contemporary approach to mental health services in rural Australia. This includes encouraging and educating the public about mental health issues and how to seek and engage in timely mental health care that is appropriate to one’s needs. Simultaneously, this review suggests a need to reconsider how the public navigates mental health services, and to redesign services that are easy to engage with, culturally safe, comfortable to use, and have technological capabilities. This may be more accurately achieved when services are designed with local issues and the community in mind via the integration of bottom-up place-based strategies and top-down place-sensitive approaches, particularly given that a one-size-fits-all approach to policy — and thus mental health service design — does not favour regions and localities [ 113 ]. It is critical that rural mental health services are invested in to remove barriers and improve health equity. The fiscal implications of such investment may be offset using this integrated approach, which leverages local and external assets, encourages workforce retention, and may reduce costs in other areas healthcare service delivery.

Strengths and limitations

The strengths of this scoping review include the use of peer-reviewed and grey literature, the full-span of the child-adult age range, and the wide variety of included studies. In addition, this scoping review applied a consistent approach to applying remoteness categories, albeit this application was not without issues. For example, Wand et al. [ 40 ] and Wand et al. [ 41 ] reports on work done in Maitland (MM1) and Dubbo (MM3). Maitland (NSW) is of particular interest in the context of remoteness settings as it has historically been described as a regional area. In the early 2000s when the Australian Bureau of Statistics was defining the most accessible category of the Accessibility/Remoteness Index of Australia (ARIA), Maitland (as well as other locations such as Wollongong, NSW and Geelong, Victoria) was included in the most accessible category [ 114 ].

Several limitations must also be considered. Firstly, many sources — particularly grey literature sources — included potentially relevant information; however, a lack of clear evidence that the data specifically pertained to those living in regional/rural/remote areas prevented many of these sources from being included. In addition, findings were limited by the available literature, especially among community service organisations, which have limited resources to generate research outputs. The search strategy was limited to 2012–2022 and did not include search terms specific to certain subgroups of the population who have been known to experience barriers to mental health services in rural areas (e.g., farmers and people from CALD backgrounds), and some search results may have been omitted as a result of this. It was not possible to discern whether findings related specifically to access or utilisation in many studies, and as such, a nuanced discussion of these dimensions is not provided. Further, the data were heterogeneous and results tended to be grouped across regional, rural, and/or remote contexts, precluding an analysis of the association between geographical area and barriers and facilitators from taking place. Future research may consider completing a comprehensive geographical analysis once additional data on the topic becomes available. Lastly, although data screening was completed by two reviewers, only one reviewer coded the extracted data into key concepts, and this may have introduced bias into the results, however the key concepts were agreed upon by the research team.

This scoping review found a number of barriers to accessing and utilising mental health services that may be overcome through initiatives that have been implemented or suggested by the government. Importantly, many of the spatial barriers associated with access and utilisation may be mitigated through innovative solutions, such as a combination of face-to-face and technology-based service provision, provided that careful consideration is given to the technological and resource limitations seen in the rural context of Australia. Parallel with this, several facilitators to accessing and utilising mental health services were noted, some of which may already be prominent in the provision of services, but could be further strengthened through additional training, service re-design, and community initiatives.

The included studies varied in their aim, setting, and study design, and many studies were grouped across MMM categories, disallowing a nuanced understanding of how barriers and facilitators operate within specific geographical contexts. This, paired with the finding that many studies were conducted at a metropolitan location, highlights the importance of conducting research within the rural setting. Additional research generated from rural areas, as well as consideration for how remoteness is measured, would assist in providing a more comprehensive understanding of the barriers and facilitators to mental health services within the geographic contexts they occur.

Data Availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Australian Capital Territory

Accessibility/Remoteness Index of Australia

Culturally and linguistically diverse

Cumulative Index of Nursing and Allied Health Literature

Emergency department

Full time equivalent

General practitioner

Lesbian, gay, bisexual, transgender, intersex, queer/questioning, asexual

Modified Monash Model

Population/concept/context

Primary Health Network

Partners in Recovery

Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews

New South Wales

Northern Territory

Rural Health Multidisciplinary Training

South Australia

Urgent care centre

Western Australia

5 References

Inder KJ, Berry H, Kelly BJ. Using cohort studies to investigate rural and remote mental health. Aust J Rural Health. 2011;19(4):171–8.

Article   PubMed   Google Scholar  

Versace VL, Skinner TC, Bourke L, Harvey P, Barnett T. National analysis of the modified Monash Model, population distribution and a socio-economic index to inform rural health workforce planning. Aust J Rural Health. 2021;29(5):801–10.

Australian Institute of Health and Welfare. Mental health workforce 2023 [Available from: https://www.aihw.gov.au/mental-health/topic-areas/workforce ].

Australian Department of Health. Modified Monash Model 2019 [Available from: https://www.health.gov.au/resources/publications/modified-monash-model-fact-sheetaccess ].

Australian Government. Deaths by suicide by remoteness areas. In: Australian Institute of Health and Welfare, editor.; 2021.

Rost K, Fortney J, Fischer E, Smith J. Use, quality, and outcomes of care for mental health: the rural perspective. Med Care Res Rev. 2002;59(3):231–65.

Fitzpatrick SJ, Perkins D, Luland T, Brown D, Corvan E. The effect of context in rural mental health care: understanding integrated services in a small town. Health Place. 2017;45:70–6.

Francis K. Health and health practice in rural Australia: where are we, where to from here? Online J Rural Nurs Health Care. 2012;5(1):28–36.

Article   Google Scholar  

Fuller J, Edwards J, Martinez L, Edwards B, Reid K. Collaboration and local networks for rural and remote primary mental healthcare in South Australia. Health Soc Care Commun. 2004;12(1):75–84.

Russell DJ, Humphreys JS, Ward B, Chisholm M, Buykx P, McGrail M, et al. Helping policy-makers address rural health access problems. Aust J Rural Health. 2013;21(2):61–71.

Australian Institute of Health and Welfare. Health workforce 2023 [Available from: https://www.aihw.gov.au/reports/workforce/health-workforce#rural ].

Penchansky R, Thomas JW. The concept of access: definition and relationship to consumer satisfaction. Med Care. 1981;19(2):127–40.

Article   PubMed   CAS   Google Scholar  

Khan AA. An integrated approach to measuring potential spatial access to health care services. Socio-Economic Plann Sci. 1992;26(4):275–87.

Article   CAS   Google Scholar  

Bourke L, Humphreys JS, Wakerman J, Taylor J. Understanding rural and remote health: a framework for analysis in Australia. Health Place. 2012;18(3):496–503.

Saurman E. Improving access: modifying Penchansky and Thomas’s theory of access. J Health Serv Res Policy. 2016;21(1):36–9.

Kaukiainen A, Kõlves K. Too tough to ask for help? Stoicism and attitudes to mental health professionals in rural Australia. Rural Remote Health. 2020;20(2):5399.

PubMed   Google Scholar  

Catherine C, Myfanwy M, Rafat H. Work challenges negatively affecting the job satisfaction of early career community mental health professionals working in rural Australia: findings from a qualitative study. J Mental Health Train Educ Pract. 2018;13(3):173–86.

Cosgrave C, Maple M, Hussain R. Work challenges negatively affecting the job satisfaction of early career community mental health professionals working in rural Australia: findings from a qualitative study. The Journal of Mental Health Training, Education and Practice; 2018.

Levesque J-F, Harris MF, Russell G. Patient-centred access to health care: conceptualising access at the interface of health systems and populations. Int J Equity Health. 2013;12(1):18.

Article   PubMed   PubMed Central   Google Scholar  

Liu C, Watts B, Litaker D. Access to and utilization of healthcare: the provider’s role. Expert Rev PharmacoEcon Outcomes Res. 2006;6(6):653–60.

Aisbett D, Boyd CP, Francis KJ, Newnham K. Understanding barriers to mental health service utilization for adolescents in rural Australia. Rural Remote Health. 2007;7(1):1–10.

Google Scholar  

Cheesmond NE, Davies K, Inder KJ. Exploring the role of rurality and rural identity in mental health help-seeking behavior: a systematic qualitative review. J Rural Mental Health. 2019;43(1):45–59.

Arksey H, O’Malley L. Scoping studies: towards a methodological framework. Int J Soc Res Methodol. 2005;8(1):19–32.

Tricco AC, Lillie E, Zarin W, O’Brien KK, Colquhoun H, Levac D, et al. PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med. 2018;169(7):467–73.

Kavanagh B, Beks H, Versace V, Quirk S, Williams L. Exploring the barriers and facilitators to accessing and utilising mental health services in regional, rural, and remote Australia: a scoping review protocol. PLoS ONE. 2022;17(12).

Australian Government Department of Health and Aged Care. Health workforce locator 2022 [Available from: https://www.health.gov.au/resources/apps-and-tools/health-workforce-locator ].

Versace VL, Beks H, Charles J. Towards consistent geographic reporting of australian health research. Med J Australia. 2021;215(11):525.

Beks H, Walsh S, Alston L, Jones M, Smith T, Maybery D et al. Approaches used to describe, measure, and analyze place of practice in Dentistry, Medical, nursing, and Allied Health Rural Graduate Workforce Research in Australia: a systematic scoping review. Int J Environ Res Public Health [Internet]. 2022; 19(3).

Veritas Health Innovation. Covidence systematic review software, Melbourne, Australia [Available from: www.covidence.org.

Munn Z, Peters MDJ, Stern C, Tufanaru C, McArthur A, Aromataris E. Systematic review or scoping review? Guidance for authors when choosing between a systematic or scoping review approach. BMC Med Res Methodol. 2018;18(1):143.

Barraclough F, Longman J, Barclay L. Integration in a nurse practitioner-led mental health service in rural Australia. Aust J Rural Health. 2016;24(2):144–50.

Cosgrave C, Maple M, Hussain R. Work challenges negatively affecting the job satisfaction of early career community mental health professionals working in rural Australia: findings from a qualitative study. J Mental Health Train Educ Pract. 2018;13(3):173–86.

Cosgrave C, Hussain R, Maple M. Retention challenge facing Australia’s rural community mental health services: service managers’ perspectives. Austr J Rural Health. 2015;23(5):272–6.

De Silva T, Prakash A, Yarlagadda S, Johns MD, Sandy K, Hansen V et al. General practitioners’ experiences and perceptions of mild moderate depression management and factors influencing effective service delivery in rural Australian communities: A qualitative study. International Journal of Mental Health Systems. 2017;11(1).

Dunstan DA, Todd AK, Kennedy LM, Anderson DL. Impact and outcomes of a rural personal helpers and mentors service. Aust J Rural Health. 2014;22(2):50–5.

Evans J, Horn K, Cowan D, Brunero S. Development of a clinical pathway for screening and integrated care of eating disorders in a rural substance use treatment setting. Int J Ment Health Nurs. 2020;29(5):878–87.

Handley TE, Kay-Lambkin FJ, Inder KJ, Lewin TJ, Attia JR, Fuller J et al. Self-reported contacts for mental health problems by rural residents: predicted service needs, facilitators and barriers. BMC Psychiatry. 2014;14.

Hussain R, Guppy M, Robertson S, Temple E. Physical and mental health perspectives of first year undergraduate rural university students. BMC Public Health. 2013;13:848.

Johnson S, Brough M, Darracott R. Unmasking depression: challenging structural oppression whilst recognising individual agency. Qualitative Social Work: Research and Practice. 2021;20(3):738–54.

Wand T, Collett G, Cutten A, Buchanan-Hagen S, Stack A, White K. Patient and staff experience with a new model of emergency department based mental health nursing care implemented in two rural settings. Int Emerg Nurs. 2021;57:N.PAG-N.PAG.

Wand T, Collett G, Keep J, Cutten A, Stack A, White K. Mental health nurses’ experiences of working in the emergency department of two rural australian settings. Issues Ment Health Nurs. 2021.

Weber M, Davis K. Food for thought: enabling and constraining factors for effective rural eating disorder service delivery. Aust J Rural Health. 2012;20(4):208–12.

Wilson RL, Cruickshank M, Lea J. Experiences of families who help young rural men with emergent mental health problems in a rural community in New South Wales, Australia. Contemp Nurse. 2012;42(2):167–77.

Batterham PJ, Kazan D, Banfield M, Brown K. Differences in mental health service use between urban and rural areas of Australia. Australian Psychol. 2020;55(4):327–35.

Clough BA, March S, Leane S, Ireland MJ. What prevents doctors from seeking help for stress and burnout? A mixed-methods investigation among metropolitan and regional-based australian doctors. J Clin Psychol. 2019;75(3):418–32.

Duggan M, Harris B, Chislett W-K, Calder R. Nowhere else to go: Why Australia’s health system results in people with mental illness getting ‘stuck’in emergency departments. 2020.

Hays C, Sparrow M, Taylor S, Lindsay D, Glass B. Pharmacists’ full scope of practice: knowledge, attitudes and practices of rural and remote australian pharmacists. J Multidisciplinary Healthc. 2020;13:1781–9.

Mirza T. First Australians deserve first-class psychiatric care: towards a better sociocultural understanding. Aust N Z J Psychiatry. 2019;53:66.

Mollah TN, Antoniades J, Lafeer FI, Brijnath B. How do mental health practitioners operationalise cultural competency in everyday practice? A qualitative analysis. BMC Health Serv Res. 2018;18(1):480.

Muir-Cochrane E, O’Kane D, Barkway P, Oster C, Fuller J. Service provision for older people with mental health problems in a rural area of Australia. Aging Ment Health. 2014;18(6):759–66.

Bowman S, Nic Giolla Easpaig B, Fox R. Virtually caring: a qualitative study of internet-based mental health services for LGBT young adults in rural Australia. Rural Remote Health. 2020;20(1):5448.

Butterfly Foundation. Maydays 2020 survey report: Barriers to accessing eating disorder healthcare & support. 2020. Available from: https://butterfly.org.au/get-involved/campaigns/maydays/

Mental Health Council of Tasmania. Submission to the Senate Community Affairs Reference Committee inquiry into accessibility and quality of mental health serices in rural and remote Australia. 2018.

National Rural Health Alliance. Mental health in rural and remote Australia. National Rural Health Alliance; 2017.

Black G, Roberts RM, Li-Leng T. Depression in rural adolescents: relationships with gender and availability of mental health services. Rural Remote Health. 2012;12(3):2092.

Crotty MM, Henderson J, Fuller JD. Helping and hindering: perceptions of enablers and barriers to collaboration within a rural South australian mental health network. Aust J Rural Health. 2012;20(4):213–8.

Dawson S, Gerace A, Muir-Cochrane E, O’Kane D, Henderson J, Lawn S, et al. Accessing mental health services for older people in rural South Australia. Australian Nurs Midwifery J. 2016;23(7):50.

Henderson J, Crotty MM, Fuller J, Martinez L. Meeting unmet needs? The role of a rural mental health service for older people. Adv Mental Health. 2014;12(3):182–91.

Henderson J, Dawson S, Fuller J, O’Kane D, Gerace A, Oster C, et al. Regional responses to the challenge of delivering integrated care to older people with mental health problems in rural Australia. Aging Ment Health. 2018;22(8):1025–31.

Newman L, Bidargaddi N, Schrader G. Service providers’ experiences of using a telehealth network 12 months after digitisation of a large australian rural mental health service. Int J Med Informatics. 2016;94:8–20.

Orlowski S, Lawn S, Antezana G, Venning A, Winsall M, Bidargaddi N, et al. A rural youth consumer perspective of technology to enhance face-to-face mental health services. J Child Fam stud. 2016;25(10):3066–75.

Orlowski S, Lawn S, Matthews B, Venning A, Wyld K, Jones G, et al. The promise and the reality: a mental health workforce perspective on technology-enhanced youth mental health service delivery. BMC Health Serv Res. 2016;16:562.

Orlowski S, Lawn S, Matthews B, Venning A, Jones G, Winsall M, et al. People, processes, and systems: an observational study of the role of technology in rural youth mental health services. Int J Ment Health Nurs. 2017;26(3):259–72.

Procter N, Ferguson M, Backhouse J, Cother I, Jackson A, Murison J, et al. Face to face, person to person: skills and attributes deployed by rural mental health clinicians when engaging with consumers. Aust J Rural Health. 2015;23(6):352–8.

Beks H, Healey C, Schlicht KG. When you’re it’: a qualitative study exploring the rural nurse experience of managing acute mental health presentations. Rural & Remote Health. 2018;18(3):1–11.

Isaacs AN, Maybery D, Gruis H. Mental health services for aboriginal men: mismatches and solutions. Int J Ment Health Nurs. 2012;21(5):400–8.

Isaacs AN, Maybery D, Gruis H. Help seeking by Aboriginal men who are mentally unwell: a pilot study. Early Intervent Psychiatry. 2013;7(4):407–13.

Isaacs AN, Sutton K, Hearn S, Wanganeen G, Dudgeon P. Health workers’ views of help seeking and suicide among Aboriginal people in rural Victoria. Aust J Rural Health. 2017;25(3):169–74.

Kidd T, Kenny A, Meehan-Andrews T. The experience of general nurses in rural australian emergency departments. Nurse Educ Pract. 2012;12(1):11–5.

Trail K, Oliffe JL, Patel D, Robinson J, King K, Armstrong G, et al. Promoting healthier masculinities as a suicide Prevention intervention in a Regional Australian Community: a qualitative study of stakeholder perspectives. Front Sociol. 2021;6:728170.

Byrne L, Happell B, Reid-Searl K. Acknowledging rural disadvantage in Mental Health: views of peer workers. Perspect Psychiatr Care. 2017;53(4):259–65.

Knight D, Plumb T, Gorey C. A STARR is born! A shining example of Integrated Care. Int J Integr Care. 2018;18:1–2.

Malatzky C, Bourke L, Farmer J. I think we’re getting a bit clinical here’: a qualitative study of professionals’ experiences of providing mental healthcare to young people within an australian rural service. Health & Social Care in the Community; 2020.

Onnis L-A, Kinchin I, Pryce J, Ennals P, Petrucci J, Tsey K. Evaluating the implementation of a Mental Health Referral Service connect to Wellbeing: a Quality Improvement Approach. Front Public Health. 2020;8:585933.

Taylor M, Kikkawa N, Hoehn E, Haydon H, Neuhaus M, Smith AC, et al. The importance of external clinical facilitation for a perinatal and infant telemental health service. J Telemed Telecare. 2019;25(9):566–71.

Richardson L, Reid C, Dziurawiec S. Going the extra mile’: satisfaction and alliance findings from an evaluation of videoconferencing telepsychology in rural western Australia. Australian Psychol. 2015;50(4):252–8.

Salinas-Perez JA, Gutierrez-Colosia MR, Furst MA, Suontausta P, Bertrand J, Almeda N, et al. Patterns of mental health care in remote areas: Kimberley (Australia), Nunavik (Canada), and Lapland (Finland). Can J Psychiatry / La Revue canadienne de psychiatrie. 2020;65(10):721–30.

Consumers of Mental Health WA. Accessibility and quality of mental health services in rural and remote Australia Submission 31. 2018. Available from: https://comhwa.org.au/resources-publications

Bridgman H, Ashby M, Sargent C, Marsh P, Barnett T. Implementing an outreach headspace mental health service to increase access for disadvantaged and rural youth in Southern Tasmania. Aust J Rural Health. 2019;27(5):444–7.

Reynish TD, Hoang H, Bridgman H, Nic Giolla Easpaig B. Mental health and related service use by sex workers in rural and remote Australia: ‘there’s a lot of stigma in society’. Culture, Health & Sexuality. 2021:1–16.

Hinton R, Kavanagh DJ, Barclay L, Chenhall R, Nagel T. Developing a best practice pathway to support improvements in indigenous Australians’ mental health and well-being: a qualitative study. BMJ Open. 2015;5(8).

Ellem K, Baidawi S, Dowse L, Smith L. Services to young people with complex support needs in rural and regional Australia: beyond a metro-centric response. Child Youth Serv Rev. 2019;99:97–106.

van Spijker BA, Salinas-Perez JA, Mendoza J, Bell T, Bagheri N, Furst MA, et al. Service availability and capacity in rural mental health in Australia: Analysing gaps using an integrated mental health atlas. Aust N Z J Psychiatry. 2019;53(10):1000–12.

Jorm AF. Mental health literacy: empowering the community to take action for better mental health. Am Psychol. 2012;67(3):231.

Solmi M, Radua J, Olivola M, Croce E, Soardo L, Salazar de Pablo G, et al. Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies. Mol Psychiatry. 2022;27(1):281–95.

Australian Government Australian Institute of Health and Welfare. Mental health services in Australia 2022 [Available from: https://www.aihw.gov.au/reports/mental-health-services/mental-health-services-in-australia/report-contents/mental-health-workforce ].

Australian Government Department of Health and Aged Care. National Mental Health Workforce Strategy Taskforce 2021 [Available from: https://www.health.gov.au/committees-and-groups/national-mental-health-workforce-strategy-taskforce ].

ACIL Allen. National Mental Health Workforce Strategy consultation draft. 2021. Available from: https://acilallen.com.au/uploads/media/NMHWS-ConsultationDraftStrategy-040821-1628234534.pdf

May JA, Scott A. The road less travelled: supporting physicians to practice rurally. Med J Aust. 2021;215(1):29–30.

State of Victoria. Royal Commission into Victoria’s Mental Health System. 2021.

Wood SM, Alston L, Beks H, Mc Namara K, Coffee NT, Clark RA, et al. The application of spatial measures to analyse health service accessibility in Australia: a systematic review and recommendations for future practice. BMC Health Serv Res. 2023;23(1):330.

Mental Health Council of Tasmania. Submission to Legislative Council Inquiry into Rural Health Services: Access to timely and appropriate mental health care in rural and remote Tasmanian communities. 2021.

Australian Government Department of Health and Aged Care. Providing health care remotely during the COVID-19 pandemic 2022 [Available from: https://www.health.gov.au/health-alerts/covid-19/coronavirus-covid-19-advice-for-the-health-and-disability-sector/providing-health-care-remotely-during-the-covid-19-pandemic ].

Park S. Digital inequalities in rural Australia: a double jeopardy of remoteness and social exclusion. J Rural Stud. 2017;54:399–407.

Mseke EP, Jessup B, Barnett T. A systematic review of the preferences of rural and remote youth for mental health service access: Telehealth versus face-to‐face consultation. Aust J Rural Health. 2023.

Robards F, Kang M, Steinbeck K, Hawke C, Jan S, Sanci L, et al. Health care equity and access for marginalised young people: a longitudinal qualitative study exploring health system navigation in Australia. Int J Equity Health. 2019;18(1):41.

Stewart V, Slattery M, Roennfeldt H, Wheeler AJ. Partners in recovery: paving the way for the National Disability Insurance Scheme. Aust J Prim Health. 2018;24(3):208–15.

Consortia HaLMMPiR. Submission to the joint standing committee on the NDIS: The provision of services under the NDIS for people with psychosocial disabilities related to mental health conditions. Joint submisson by the Hume and Loddon Mallee Murray Partners in Recovery Consortia. 2017.

Hancock N, Smith-Merry J, Gillespie JA, Yen I. Is the Partners in Recovery program connecting with the intended population of people living with severe and persistent mental illness? What are their prioritised needs? Aust Health Rev. 2016;41(5):566–72.

Isaacs AN, Dalziel K, Sutton K, Maybery D. Referral patterns and implementation costs of the Partners in Recovery initiative in Gippsland: learnings for the National Disability Insurance Scheme. Australasian Psychiatry. 2018;26(6):586–9.

Productivity Commission. 5-year Productivity Inquiry: Advancing Prosperity. Canberra., ; 2023. Contract No.: Inquiry Report no. 100. Available from: https://www.pc.gov.au/inquiries/completed/productivity/report

Mehta N, Clement S, Marcus E, Stona A-C, Bezborodovs N, Evans-Lacko S, et al. Evidence for effective interventions to reduce mental health-related stigma and discrimination in the medium and long term: systematic review. Br J Psychiatry. 2015;207(5):377–84.

Article   PubMed   PubMed Central   CAS   Google Scholar  

Santana MJ, Manalili K, Jolley RJ, Zelinsky S, Quan H, Lu M. How to practice person-centred care: a conceptual framework. Health Expect. 2018;21(2):429–40.

Archer J, Bower P, Gilbody S, Lovell K, Richards D, Gask L et al. Collaborative care for depression and anxiety problems. Cochrane Database of Systematic Reviews. 2012(10).

Curtis E, Jones R, Tipene-Leach D, Walker C, Loring B, Paine S-J, et al. Why cultural safety rather than cultural competency is required to achieve health equity: a literature review and recommended definition. Int J Equity Health. 2019;18(1):174.

Wainer J, Chesters J. Rural mental health: neither romanticism nor despair. Aust J Rural Health. 2000;8(3):141–7.

Pretty GH, Chipuer HM, Bramston P. Sense of place amongst adolescents and adults in two rural australian towns: the discriminating features of place attachment, sense of community and place dependence in relation to place identity. J Environ Psychol. 2003;23(3):273–87.

Alston L, Bourke L, Nichols M, Allender S. Responsibility for evidence-based policy in cardiovascular disease in rural communities: implications for persistent rural health inequalities. Aust Health Rev. 2020;44(4):527–34.

Alston L, Versace VL. Place-based research in small rural hospitals: an overlooked opportunity for action to reduce health inequities in Australia? Lancet Reg Health–Western Pac. 2023;30.

Alston L, Field M, Brew F, Payne W, Aras D, Versace VL. Addressing the lack of research in rural communities through building rural health service research: establishment of a research unit in Colac, a medium rural town. Aust J Rural Health. 2022;30(4):536.

Walsh S, Lyle DM, Thompson SC, Versace V, Browne LJ, Knight S et al. The role of national policies to address rural allied health, nursing and dentistry workforce maldistribution. 2020.

Australian Government Department of Health and Aged Care. Rural Health Multidisciplinary Training (RHMT) program 2022 [Available from: https://www.health.gov.au/our-work/rhmt ].

Sotarauta M. Place-based policy, place sensitivity and place leadership. Working paper 46/2020: Tampere University; 2020.

Australian Bureau of Statistics. ABS views on remoteness 2001 2001 [Available from: https://www.ausstats.abs.gov.au/ausstats/free.nsf/0/FCC8158C 85424727CA256C0F000035 75/$File/12440_2001.pdf.

Batterham PJ, Calear AL, Christensen H, Carragher N, Sunderland M. Independent effects of mental disorders on suicidal behavior in the community. Suicide and Life-Threatening Behavior. 2018;48(5):512–21.

Australian Institute of Health and Welfare. Emergency department care 2017–18: Australian hospital statistics Canberra: Australian Institute of Health and Welfare; 2018 [Available from: https://www.aihw.gov.au/getmedia/9ca4c770-3c3b-42fe-b071-3d758711c23a/aihw-hse-216.pdf.aspx?inline=true ].

Mental Health Services Australia A. [Available from: https://mhsa.aihw.gov.au/services/medicare/ ].

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BEK, HB, and VLV are funded by the Rural Health Multidisciplinary Training (RHMT) program. LJW is supported by a National Health and Medical Research Council (NHMRC) Emerging Leadership Fellowship [1174060].

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Additional Table 3: Barriers and/or facilitators of access and/or utilisation factors in regional, rural, and remote Australia

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Kavanagh, B.E., Corney, K.B., Beks, H. et al. A scoping review of the barriers and facilitators to accessing and utilising mental health services across regional, rural, and remote Australia. BMC Health Serv Res 23 , 1060 (2023). https://doi.org/10.1186/s12913-023-10034-4

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Tourette Syndrome Treatment Updates: a Review and Discussion of the Current and Upcoming Literature

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Purpose of Review

This study aims to examine the treatments currently available for Tourette syndrome (TS) and to discuss evolving therapies, spanning behavioral, pharmacologic, complementary and alternative medicine, and neuromodulation approaches.

Recent Findings

Behavioral therapies have undergone several modifications to improve accessibility, including transitioning to a virtual format which is particularly important in the current pandemic. There are several recent or ongoing pharmacologic studies that have shown promise including the selective D1 receptor antagonist ecopipam and various cannabinoid compounds. Adaptive DBS may enable the physiologic markers of tics to determine stimulation parameters and improve tic outcomes related to neuromodulation.

In recent years, there has been a wealth of research across multiple treatment domains in the TS field. This review highlights exciting and new potential options for the future treatment of patients with TS.

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Introduction

Tourette syndrome (TS) is a childhood-onset disorder in which multiple motor tics and at least one phonic tic occur, lasting beyond a year and typically fluctuating over time. Although in many cases tics can be mild and non-bothersome, in others, tics can cause physical discomfort, academic and professional detriment, and social disability. Tics in TS may be associated with a number of comorbidities, including anxiety, attention deficit hyperactivity disorder (ADHD), and obsessive–compulsive disorder (OCD). Genetic factors drive some portion of risk, and hyperactivity in dopamine circuitry seems to play a pivotal role in the pathophysiology. Management begins with education about the nature of tics. When tics impair quality of life, there are many established and evolving treatment options that may be considered. This review will discuss treatment updates for TS, including behavioral and other non-pharmacologic interventions, pharmacologic strategies, and neuromodulatory approaches.

Non-pharmacologic Interventions

Although pharmacotherapy plays a major role in the treatment of TS, medication side effects are common and may accumulate over time. For this reason, more conservative approaches are often considered first-line, including psychoeducation, behavioral interventions, and biofeedback.

Psychoeducation and Supportive Therapy (PST)

Psychoeducation and supportive therapy (PST) can help to mitigate misunderstandings of TS, reduce perceived stigmas, and provide age-appropriate explanations for TS and associated comorbidities [ 1 ]. One meta-analysis found that PST improves knowledge and misconceptions regarding TS [ 2 ]. However, a diagnostic label in isolation may lead to negative expectations of certain behaviors or even exacerbate symptoms [ 2 ]. Therefore, it is important that information is used to increase awareness and promote acceptance [ 2 ]. There is evidence for further reduction in tics when PST is added to pharmacotherapy, relative to pharmacotherapy alone [ 3 ]. PST has expanded to incorporate video footage [ 2 ] and tele-psychoeducation strategies effectively [ 4 ].

Reliable information is critical to supporting well-being with tics. Virtual communication and social media use skyrocketed in the face of the COVID-19 pandemic, and individuals, particularly adolescents, increasingly turn to the Internet and social media for healthcare information [ 5 , 6 ]. The increased consumption of information about TS from public sources with variable accuracy, combined with social isolation and need for connection, may have contributed to increased frequency of explosive onset functional tic-like behaviors [ 7 ]. Social media “influencers” have posted videos with very particular and extreme manifestations, and online communities have encouraged sharing tics and rating their severity. Although online support groups offer many positives with regard to acceptance, community, and information sharing, they may unintentionally propagate inaccurate ideas about tics and influence tic expression given the suggestibility of tics [ 8 ]. Therefore, it is equally important to educate patients about sources where reliable information about TS is available.

Multiple treatment guidelines recommend clinicians use psychoeducation to help educate patients, teachers, and peers about the natural history of TS [ 9 ••, 10 ••, 11 ]. Strategies to disseminate PST have recently been outlined in a guide by Wu and McGuire (2018) [ 12 ]. Combining education on an individual level with dissemination of resources that can aide educators or family members, such as those available through Tourette syndrome-focused national organizations, is advisable.

Behavioral Interventions

Behavioral interventions have the advantage of being effective at reducing tics without significant adverse effects and therefore are the first-line treatment according to several treatment guidelines [ 9 ••, 10 , 11 , 13 ••, 14 ••]. At least one study has demonstrated that behavioral interventions are comparable to pharmacotherapy at reducing tics [ 15 ]. Exposure and response prevention (ERP) exposes patients to the unpleasant sensation associated with a premonitory urge, simultaneously teaching habituation to the urge and how to prevent the tic from occurring [ 16 ]. Habit reversal therapy (HRT), which involves awareness training, competing response practice, and habit control motivation and generalization training, was one of the earliest behavioral interventions successfully used to reduce tics [ 17 ]. There is evidence that both of these interventions are effective at reducing tics [ 18 – 25 ]. Since then, HRT has been expanded into comprehensive behavioral intervention for tics (CBIT), which includes psychoeducation, relaxation training, behavioral rewards, and function-based interventions [ 16 ]. Several critiques of CBIT, including that it is only useful for patients with mild tics, that it requires considerable effort for patients, that the tic improvements are modest and not sustained over time, and that CBIT may result in tic substitution or worsening, have been disproven [ 26 , 27 ]. Although CBIT has not been shown to improve psychiatric comorbidities[ 24 , 28 ], CBIT has repeatedly been shown to reduce tic frequency and severity with long-term improvement [ 29 – 32 ].

Modifications of Existing Behavioral Interventions

The original CBIT study was geared toward pediatric TS patients aged 9–17 years [ 30 ]. Since then, CBIT has undergone a variety of modifications (Table 1 ). CBIT has been adapted via “The Opposite Game” for children as young as 5–8 years of age [ 33 ]. An educational HRT-training DVD has been incorporated for families at home in parallel to in-person CBIT [ 34 ]. CBIT has been expanded to group settings [ 35 – 38 ]. Cognitive psychophysiological approaches to address both tics and cognitive issues have been created [ 39 , 40 ]. The typical 8 sessions delivered over 10 weeks has been reduced to 4 sessions delivered over 3 months [ 41 ] and, in some cases, condensed into a single week [ 42 , 43 ]. These CBIT modifications have all been shown to reduce tics as effectively as traditional CBIT and improve accessibility, especially in communities in which there is a shortage of CBIT-trained providers.

Virtual or Tele-behavioral Interventions

Flexible methods of CBIT delivery have become especially important during the COVID-19 pandemic, which fueled rapid widespread implementation of telehealth. When delivered virtually, there are similar reductions in tic severity comparable to in-person behavioral interventions[ 44 – 46 ], and subjects found telehealth delivery to be an acceptable format [ 44 ]. A virtual, self-guided format provided by the website TicHelper.com is available for independent patient use [ 47 ]. An alternative virtual platform called TicTrainer incorporates ERP-like strategies via a self-guided website [ 48 ], and additional virtual CBIT programs have recently been proposed [ 49 , 50 ]. However, further work is needed to establish the comparative efficacy of these modalities.

Biofeedback

Based on the observation that autonomic changes impact tic expression and frequency [ 51 ], biofeedback has been attempted to exert voluntary control over symptoms by providing feedback through psychological or physiological means [ 52 ]. Studies using electrodermal biofeedback have been mixed [ 52 , 53 ], but a recent fMRI neurofeedback study was able to demonstrate significant reduction in tics compared to sham neurofeedback [ 54 ].

In summary, behavioral therapies are generally low-risk. When accessible, they are recommended as first-line or adjunctive treatment components when tic severity does not call for urgent pharmacologic intervention or when individual preference or characteristics do not make them unsuitable.

Pharmacologic Interventions

In spite of the widespread use of pharmacotherapy for the treatment of TS, there is a surprising lack of large, well-controlled studies for medication efficacy in TS [ 55 ]. Medications should be considered in patients if more conservative treatments such as behavioral interventions are ineffective or if the tics are severe [ 56 •]. Although there are a wide variety of medication options for TS, only 3 medications are currently FDA-approved for use in TS: haloperidol (> 3 years old), pimozide (> 12 years old), and aripiprazole (ages 6–18 years old) [ 55 ]. In clinical practice, choosing which medication to use depends on tic severity, comorbidities, and potential adverse effects.

Alpha-2-adrenergic Agonists

Due to their relatively safer side effect profile, the medications that are most often recommended as first-line pharmacotherapy are alpha-2-adrengergic agonists, which may work to suppress the sympathetic nervous system [ 57 •]. Although early studies of the effectiveness of clonidine were mixed [ 58 ], clonidine has been shown to be more effective than placebo at reducing tics [ 59 ] and additionally helps improve tics in patients with comorbid TS and ADHD [ 60 ]. The clonidine adhesive patch has additionally been shown to be safe and effective for TS management [ 61 – 63 ] and is comparable to haloperidol [ 64 – 66 ]. Guanfacine has had mixed results with some studies demonstrating safety and efficacy [ 67 , 68 ], but others not demonstrating significant tic reduction [ 69 , 70 ]. Therefore, clonidine is recommended with moderate confidence in the evidence, whereas guanfacine is recommended with low confidence [ 9 ••]. However, guanfacine may be less sedating because of selectivity for alpha-2 receptors and therefore is often chosen over clonidine in clinical practice [ 56 •]. To date, guanfacine and clonidine have not been directly compared.

GABAergic Medications and Anticonvulsants

Given that dysfunctional GABA pathways may contribute to the underlying etiology of TS, medications that act on GABA receptors or influence GABA concentrations have been explored for use in the treatment of TS [ 71 ]. Topiramate, a broad-spectrum antiepileptic, has been studied in a double-blind, placebo-controlled study with significantly reduced tics compared to placebo [ 72 ], and a retrospective study found similar results [ 73 ]. Side effects include paresthesias, cognitive slowing, and decrease in appetite leading to weight loss, as well as increased risk of glaucoma and kidney stones [ 57 •]. Levetiracetam had mixed results in placebo-controlled trials: one small study with improvement [ 74 ] and two others without [ 75 , 76 ]. Clonazepam and baclofen have been reported in case reports and case series or open-label reports but are without RCTs demonstrating tic reduction [ 57 •, 77 •]. Baclofen showed improvement in impairment scores but not tics in one small RCT [ 78 ]. Based on a meta-analysis of treatments for TS, topiramate was found to possibly have some benefit compared to placebo, whereas there is insufficient evidence to determine if levetiracetam, clonazepam, or baclofen would have any more benefit compared to placebo [ 9 ••]. In practice, topiramate can be useful when weight gain from neuroleptics has occurred or is undesirable. Benzodiazepines may have a limited role when comorbid anxiety is prominent, weighing benefit against risk of dependence, and baclofen may be considered if severe muscle pain or tension is present.

Dopamine Receptor Blocking Agents (Neuroleptics)

Due to potential significant side effects, dopamine receptor blocking agents are generally used as second-line agents [ 79 ]. A recent meta-analysis summarized most common side effects: increased risk of weight gain with risperidone and aripiprazole; elevated prolactin levels with pimozide, haloperidol, and metoclopramide; increased risk of sedation with risperidone, aripiprazole, tiapride, clonidine, and guanfacine; and increased risk of extrapyramidal symptoms or parkinsonism with pimozide, haloperidol, and risperidone [ 13 ••]. In addition, serious cardiac side effects such as QTC prolongation can occur, especially in pimozide and ziprasidone [ 56 •, 80 ]. In practice, these potential side effects may occur with any of the medications in this class.

Although haloperidol was one of the earliest dopamine blocking agents to demonstrate efficacy for the treatment of TS, follow-up studies have shown that it has more serious side effects and is inferior to other agents [ 57 •]. Thus, haloperidol is typically used only after other medications have failed. Ziprasidone, fluphenazine, olanzapine, and quetiapine are antipsychotics that are sometimes recommended by experts in the field; however, evidence to support their use in TS is limited [ 77 •]. Studies have demonstrated that both pimozide and risperidone lead to significant tic reduction in comparison to placebo as well as in comparison to several alternative dopamine blocking agents [ 57 •, 77 •]. Aripiprazole is an atypical neuroleptic with partial agonist activity on D2 dopamine receptors, as well as serotonergic effects. Two meta-analyses found that across 17 RCTs, aripiprazole was well-tolerated, with significantly less side effects and similar efficacy compared to placebo or other agents [ 81 , 82 ]. A recent RCT compared aripiprazole to intravenous valproic acid and determined that both treatments led to similar significant reduction in tics, though the intravenous valproic acid group responded to treatment faster [ 83 ].

Benzamides such as tiapride, sulpiride, and amisulpiride are D2-blocking agents that are commonly used to treat TS outside of the USA [ 77 •]. In contrast to other dopamine receptor blocking agents, benzamides have fewer extrapyramidal side effects [ 77 •, 84 ]. Most evidence for benzamides comes from remote open-label studies or case reports [ 77 •]. There have been no recent studies assessing the efficacy of these medications.

A recent meta-analysis found that there is moderate confidence that haloperidol, risperidone, aripiprazole, and tiapride would lead to tic reduction compared to placebo, whereas pimozide and ziprasidone were only possibly more likely to receive benefit in tic severity compared to placebo [ 13 ••].

Ecopipam is a first-in-class drug that has selective D1 receptor antagonism. An open-label study demonstrated that ecopipam was safe and led to significant tic reduction [ 85 ], and a follow-up placebo-controlled trial demonstrated similar results [ 86 ]. A phase IIb trial called the D1AMOND study is currently underway to test ecopipam further (NCT04007991) with a corresponding open-label extension following the randomization period (NCT04114539).

VMAT2 Inhibitors

Biogenic amines including dopamine are transported by vesicular monoamine transporter-2 (VMAT-2). VMAT2 inhibitors work by depleting dopamine pre-synaptically [ 56 •]. In open-label studies, tetrabenazine has reduced tics [ 87 , 88 ]. Deutetrabenazine is an isomer of tetrabenazine with a longer half-life and less risk of side effects [ 77 •]. Open-label studies have demonstrated that deutetrabenazine is safe and effective for tic disorders [ 89 ]. However, the phase 2/3 ARTIST1 and phase 3 ARTIST2 trials failed to reach the primary end point of tic reduction (NCT03567291, NCT03571256). The safety and tolerability of valbenazine for tics were established in the T-Force study but placebo-controlled trials in adults (T-Forward), pediatrics at fixed doses (T-Force green), and pediatrics at optimized doses (T-Force gold), as well as open-label extension studies (T-Fusion and T-Force gold +) failed to meet the primary endpoint [ 90 ]. As a result, this class of medications is often reserved for cases that have been refractory to other classes or in whom potential side effect profiles favor avoiding other classes.

Cannabinoids

The two main types of cannabinoids are tetrahydrocannabinol (THC) (psychoactive) and cannabidiol (CBD) (non-psychoactive) [ 55 ]. Dronabinol is a synthetic version of THC and nabiximol is part THC and part CBD [ 55 ]. Patients self-reporting tic improvement following use of cannabinoids have led to interest in studying them systematically [ 91 ]. A placebo-controlled trial of a single dose of THC led to significant reduction in tics [ 92 ] and when administered for 6 weeks led to significant improvement in subjects’ perceived tic severity and quality of life as well as trends toward reduction in tic scores [ 93 ]. A Cochrane review determined that there was not enough evidence to support whether or not cannabinoids are an effective treatment for TS [ 94 ]. Side effects include dry mouth, nausea/vomiting, headache, fatigue, disorientation, and anxiety [ 95 ]. Risks that may be specific to the developing brain have not been fully explored.

A recent survey revealed that in patients who have independently used cannabinoids for TS treatment, patients tend to favor THC-rich cannabis over dronabinol or nabiximols [ 96 ]. There are currently several ongoing trials. An RCT was planned with different ratios of THC and CBD versus placebo to determine if a specific composition would have better safety and efficacy; however, the study was terminated due to slow enrollment (NCT03247244). A study comparing a THC and CBD compound in a 1:1 ratio versus an inert oil has been registered, but results are not yet available (ACTRN12618000545268). Similarly, the CANNA-TICS protocol plans to test nabiximol in comparison to placebo [ 97 ].

There have also been attempts to modify the endogenous endocannabinoid system in the treatment of TS. Lu-AG06466 (previously referred to as ABX-1431) is a selective inhibitor of monoacylglycerol lipase (MAGL), which prevents the breakdown of an endogenous ligand of the endocannabinoid system [ 95 ]. In a single-dose placebo-controlled crossover study evaluating Lu-AG06466 in 20 adult patients with TS, there was significant improvement in tic scores [ 98 ]. However, a follow-up multicenter, double-blind, randomized, placebo-controlled trial found no significant differences in tic severity between Lu-AG06466 and placebo at 8-week follow-up [ 99 ]. In addition to these studies, there are active trials evaluating palmitoylethanolamide (PEA), which is an endogenous fatty acid amide that mimics the properties of cannabinoids [ 95 ]. Furthermore, PEA may reduce the side effects associated with cannabinoids, making it an appealing compound to study in combination with traditional cannabinoids [ 95 ]. A phase 2 open-label study evaluating dronabinol in combination with PEA (THX-110) found an averaged YGTSS reduction of 20% compared to baseline [ 100 ]. A larger, placebo-controlled trial is currently under development (NCT03651726). In addition, the psychoactive properties of cannabinoids need to be accounted for when designing placebo-controlled trials in the future.

Botulinum Toxin Injections

Botulinum toxin inhibits acetylcholine release at the neuromuscular junction, leading to temporary relaxation of the muscle injected [ 77 •]. There have been several case reports [ 101 – 104 ] and open-label studies [ 105 – 108 ] that demonstrated botulinum toxin led to significant reduction in tics. However, only one randomized, placebo-controlled trial has been conducted with botulinum toxin in the TS population [ 109 ], which was the only study which met the criteria for a recent Cochrane review, classifying the evidence for botulinum toxin in TS as low-quality [ 110 ]. A meta-analysis of treatments for TS has determined that onabotulinumtoxin A injections are probably more likely to reduce tic severity compared to placebo [ 13 ••]. In practice, botulinum toxin injections may be most helpful for specific focal tics such as blinking, facial movements, neck jerking, and disabling coprolalia or loud vocal tics (vocal cord injections). Risks generally relate to excessive weakness of injected or surrounding muscles, so careful dosing and expert injection are critical.

Complementary Alternative Medicine (CAM) and Supplementation

Due to the side effects associated with pharmacologic treatments, there is increasing interest in using complementary alternative medicine (CAM). A wide range of CAM modalities including meditation, vitamins, prayer, and other homeopathic regimens have been implemented, though not well-studied systematically [ 111 ].

Two recent meta-analyses reported that traditional Chinese medicine (TCM) had the potential to reduce tics relative to placebo or western medicine [ 112 , 113 •]. Ningdong granule (NDG) is a combination of plant, animal, and placental products thought to modulate the D2 receptor pathway and has been shown to be well-tolerated and effective at reducing tics compared to placebo [ 77 •]. Choudongning (CDN) capsule has shown promise in several double-blind, placebo-controlled studies [ 113 •, 114 ,  115 ]. 5-Ling granule (5-LGr) contains 11 different herbs and has shown comparable efficacy to tiapride with better tolerability [ 116 ]. Another proprietary polyherbal product called Changma Xifeng was reported to have similar efficacy as western medicine [ 117 , 118 ]. In addition, a placebo-controlled trial is ongoing for tic reduction from Yi-Gan San, a traditional herbal remedy that has been used to reduce restlessness and agitation in children (NCT03564132). The underlying mechanism for potential tic reduction by these herbal supplements is unknown. Acupuncture for TS was the subject of a recent systematic review which found that across 22 RCTs, acupuncture was identified as superior in the overall effectiveness rate, YGTSS score, number of adverse events, and recurrence rates during follow-up [ 119 ]. This review had similar conclusions to other systematic reviews on the topic [ 120 , 121 ]. According to a recent meta-analysis, NDG (formulated by Zhao) and 5-LGr were found to be probably more likely than placebo to reduce tic severity [ 9 ••]. Generalizability of the findings of these studies in other tic populations still needs to be established.

Other forms of supplementation also show promise. Taurine, a GABA-receptor agonist, when added to tiapride significantly improved tics compared to placebo, without significantly more adverse events [ 122 ]. Whether vitamin D levels correlate with tic severity is unclear [ 123 , 124 ], but at least one study has demonstrated that vitamin D supplementation led to significant improvement in tic symptoms [ 125 ]. Further investigation is needed to confirm benefit and determine if deficiency is needed in order to have potential benefit. In addition to supplementation, a small open-label study described an oral splint (typically used to treat temporomandibular joint disorders) as being helpful for tics. The authors hypothesized that proprioceptive input to the insular cortex might have a modulating effect on tics but acknowledged that a placebo effect may be contributory [ 126 ].

O ngoing Clinical Trials.

There are several active or recent studies regarding novel compounds or innovative treatments for TS. There is an ongoing trial investigating atomoxetine, a noradrenaline reuptake inhibitor, which is hypothesized to improve response inhibition in individuals with TS (NCT04354103). AZD5213 is an H3-receptor antagonist that has been assessed for safety and tolerability in the TS population (NCT01904773) but unfortunately has not shown any significant difference compared to placebo. Pimavanserin is a serotonin receptor inverse agonist currently being investigated in an open-label phase 1 pilot study (NCT04794413). Since serotonin is low in co-occurring conditions such as depression, anxiety, and OCD, this medication may be an appropriate treatment choice for patients with TS.

There have also been studies investigating the gut–brain axis. Lactobacillus plantarum PS128 is a probiotic that can modulate neurotransmitter levels in the brain [ 127 ]. At least one study has demonstrated improvement in oppositional defiant behaviors in individuals with autism [ 127 ], and a trial is currently underway to investigate whether PS128 can reduce tic severity in patients with TS (NCT04805385). Similarly, a case report and an open-label study found that 4/5 patients had significant reduction in YGTSS scores following fecal microbiota transplantation [ 128 , 129 ].

Studies have also evaluated whether medication can augment behavioral therapies. D-cycloserine is an antibiotic which has been shown to enhance learning. A recent study demonstrated significant tic reduction with D-cycloserine + HRT compared to placebo + HRT [ 130 ]. A follow-up study is underway to determine if there are long-lasting effects when D-cycloserine is provided prior to the start of each HRT session (NCT04357951).

There is a great deal of potential to continue improving the pharmacologic treatments available for TS. Although results for VMAT2 inhibitor studies have been disappointing, studies of ecopipam, cannabinoids, intravenous valproic acid, adjunctive taurine, vitamin D, and D-cycloserine have all demonstrated potential therapeutic benefit [ 131 ]. Larger, placebo-controlled studies are needed to confirm these findings.

Non-invasive Brain Stimulation (NIBS)

Though not yet having a role in routine clinical care of TS, the following NIBS have been studied: transcranial magnetic stimulation, transcranial direct current stimulation, and peripheral nerve stimulation.

Transcranial Magnetic Stimulation (TMS)

Repetitive transcranial magnetic simulation (rTMS) at frequencies of 5 Hz and higher leads to excitatory modulation, whereas rTMS at low frequencies of 1 Hz leads to inhibitory modulation. Many case reports and open-label studies using inhibitory stimulation targeted at the supplementary motor area (SMA) demonstrate very promising results [ 132 – 138 ], while other studies have shown no significant differences following rTMS [ 139 , 140 ], and RCTs have shown trends toward improvement in tics without significant differences between active and sham stimulation (Table 2 ) [ 135 , 141 ]. A more recent randomized rTMS study which targeted the bilateral parietal cortex showed significant improvements in tic scores compared to sham stimulation [ 142 ]. One meta-analysis concluded that rTMS appears to be an appropriate option for treatment-resistant tic [ 143 ]. rTMS may also be a tool to address comorbid symptoms, including OCD [ 144 – 146 ]. Other innovative approaches include combining rTMS with CBIT, of which three trials are actively recruiting (NCT04578912, NCT04795908, NCT03844919). rTMS appears to be safe in adult and pediatric populations [ 133 , 134 , 136 , 141 ]. However, heterogeneity between stimulation targets, number of pulses, and sample size may account for variability in outcomes, and further work is needed to determine optimal stimulation parameters.

Transcranial Direct Current Stimulation (tDCS)

Transcranial direct current stimulation (tDCS) uses constant, low current delivered via electrodes attached directly to the scalp. Anodal stimulation increases cortical excitability, whereas cathodal stimulation decreases cortical excitability [ 147 ]. As opposed to rTMS, which is expensive, requires specialized training to administer, and travels to a center which has a TMS machine, tDCS is cheap, portable, and easy to administer [ 147 ]. Thus far, results have been heterogenous, with many studies demonstrating significant improvement in tic severity following active stimulation [ 147 – 152 ], but only a few demonstrate a significant difference between active and sham stimulation (Table 3 ) [ 148 , 149 ]. In addition, many studies were of open-label study design, so it is unclear how much a placebo response led to the improvement in tic severity [ 151 – 153 ]. Currently, one trial is actively recruiting to assess efficacy of 1 mA tDCS to the SMA (NCT03401996).

Peripheral Nerve Stimulation

Case reports of patients who were treated with vagal nerve stimulation (VNS) for unrelated causes found that tics also improved when the VNS was turned on [ 154 , 155 ]. More recently, a case report used transcutaneous VNS combined with breathing exercises to reduce tics [ 156 ]. It is currently unclear how VNS influences tics but may be through reduction of the “signal-to-noise ratio” hypothesized to help decipher appropriate motor signals from background noise [ 157 ].

It is also known that certain frequency bands, in particular alpha or mu (8–14 Hz) and beta (15–30 Hz), are associated with suppression of movement, and entraining these cortical oscillations could theoretically lead to the suppression of tics [ 158 ]. In a recent study, rhythmic pulses delivered at 12 Hz to the median nerve led to entrainment of mu-band oscillations in the brain and significant reduction in tic frequency and severity as well as the urge to tic [ 159 ]. A follow-up, sham-controlled study is currently recruiting in an attempt to replicate these results (NCT04731714).

Cranial Electrotherapy Stimulation (CES)

Cranial electrotherapy stimulation is a technique which uses a small handheld device to stimulate the brain with a small amount of current. At least one study has combined CES with functional MRI to demonstrate stronger functional connectivity in the anterior cingulate cortex and weaker activity in the SMA, suggesting that CES may suppress disinhibited brain activity associated with TS [ 160 ]. A randomized, double-blind, sham-controlled trial known as the Study of CES as an Add-on Treatment for Tic Disorders (SCATT study) is currently underway to determine if CES is a therapeutically meaningful tool to reduce tic severity (NCT03705988).

Deep Brain Stimulation (DBS)

Approximately 5% of patients with TS are refractory to more conservative therapies, and DBS may therefore be a valuable treatment option [ 161 ]. However, it is important to be aware of patient selection, target selection, and surgical complications before proceeding with surgical intervention for TS.

Candidate Selection

Guidelines for DBS candidate selection for TS were published in 2015 and include 5 main components: (1) a diagnosis of TS which fulfills DSM V criteria made by a clinician with expertise in tic disorders; (2) tics cause significant disability in daily life; (3) YGTSS severity is ≥ 35 for at least 1 year; (4) patients have tried and failed conservative treatment in at least three different medication classes and behavioral therapy; and (5) comorbid symptoms such as ADHD and OCD are stable for at least 6 months [ 162 ].

These recommendations were refined further recently. First, the presence of malignant tics may not be captured by a YGTSS score, and therefore, tics leading to ≥ 2 emergency department visits or 1 hospitalization may also fulfill the tic severity requirement [ 163 ••]. Second, using quality of life scales to determine if the tics or comorbid symptoms are the primary cause of disability is relevant [ 163 ••]. Third, due to known fluctuations of tics, duration of treatment attempt should be at least 4–12 weeks [ 163 ••].

Although the natural history of TS suggests tics may improve with age and without surgical intervention, there is growing evidence that DBS is safe and efficacious in the pediatric TS population [ 164 , 165 , 166 •]. DBS has been used to successfully treat patients as young as 12 years of age [ 165 ]. Early intervention with DBS may reduce the risk of tic-induced social isolation, minimize harm from malignant tics, and minimize the impact of tics in the academic and professional setting during crucial developmental years [ 164 ]. Although there are no strict age cutoffs for DBS in the TS population, the decision to surgically intervene in the pediatric population remains a topic of controversy, and it is recommended that a local ethics committee review cases for patients 18 years old or younger [ 162 , 166 •, 167 ].

International TS DBS Registry

In collaboration with the Tourette Association of America (TAA), several centers joined together in 2012 to create the International TS DBS Registry [ 168 ]. There are currently 34 different centers contributing data, with 340 registered patients representing 700 DBS leads. The majority of patients have been implanted with bilateral leads, and collectively, a 44% decrease in total YGTSS score across all targets 1 year following DBS surgery compared to baseline has been recorded ( https://tourettedeepbrainstimulationregistry.ese.ufhealth.org/ , accessed 11/4/2021). Both motor and vocal tics demonstrate improvement. The strengths of the TS registry are that it pools cases from across the globe to generate meaningful comparisons between patients, with the goal of providing recommendations for optimal patient and target selection, sharing effective stimulation paradigms, and facilitating regulatory approval [ 168 ].

Target Selection

At least 9 different target sites have been reported in the literature, with the thalamus, anterior globus pallidus internus (aGPi), and nucleus accumbens and anterior internal capsule (ALIC-NAc) as some of the most common targets [ 167 ]. Given the complexity and heterogeneity amongst patients with TS, identifying one specific target site for all patients with TS may not be feasible or productive. In fact, understanding individual differences in patients with TS may lead to individualizing the DBS target locations for each patient. For example, tic-predominant TS may be more effectively modulated by thalamic targets, whereas TS with predominant comorbid symptoms may be more effectively modulated by pallidal or ALIC-NAc targets, although further studies are needed to support these observations [ 167 , 169 – 171 ].

DBS Outcomes

Overall, there is a 30–50% improvement in tics following DBS, regardless of target [ 161 , 172 ]. There have been a number of small studies targeting the thalamus [ 173 – 178 ] and GPi [ 176 , 179 , 180 ] that have demonstrated significant improvement in tic severity. A recent study comparing active and sham stimulation in 8 adult TS patients demonstrated significantly more tic reduction in the active stimulation phase compared to the sham stimulation phase [ 181 ]. Combining thalamic and pallidal stimulation did not significantly reduce tics more compared to either type of stimulation alone [ 182 ]. In addition, younger age, lower baseline YGTSS, and more severe baseline impairment scores have been shown to predict better DBS outcomes [ 166 •, 169 , 181 ]. Complications from DBS in the TS population occur at similar rates to DBS for other indications [ 167 ].

Adaptive Stimulation

Local field potentials (LFPs) have specific characteristics that correlate with tics and can theoretically be analyzed by the DBS system in a “closed-loop” paradigm to adjust stimulation parameters independently [ 183 ]. Bursts of oscillations in the theta range have been associated with worse motor tic severity [ 184 ]. Adaptive stimulation minimizes the amount of unwanted stimulation when patients are in a tic-free state and also reduces the power requirements of the IPG [ 170 ]. At least one case report demonstrated significant tic reduction with adaptive neurostimulation in response to a 5–15 Hz oscillatory band, which was comparable to the tic reduction seen with scheduled stimulation, as well as a 63% improvement in the estimated battery life [ 185 ].

Conclusions

Treatment options have greatly evolved over the past several decades, enabling more opportunities to improve the quality of life for patients with TS. Modifications to existing therapies have enabled behavioral interventions to be more accessible through virtual CBIT platforms, condensing the number of CBIT sessions to occur over a shorter timeframe and providing behavioral therapy in a group setting. These modifications are especially relevant during the COVID-19 pandemic, in which resource allocation and adaptation to telemedicine are paramount. There are several potentially promising pharmacologic options on the horizon which may expand the ability to reduce tics, hopefully with less adverse effects. In addition, there are many CAM options via TCM or vitamin supplementation that are low-risk and may expand the options for primary or adjuvant therapy. Finally, the future of the neuromodulation realm carries many exciting developments, including the use of NIBS to ameliorate tics as well as closed-loop DBS which can tailor stimulation to a patient’s unique physiology. While the most effective treatment for TS still depends on the individual symptoms and needs of the patient, these behavioral, pharmacologic, and neuromodulatory developments will continue to pave the way for the future treatment of TS.

Key: ADHD , attention deficit hyperactivity disorder; CBIT , Comprehensive Behavioral Intervention for Tics; COSA , Child Occupational Self-Assessment; CTD , chronic tic disorder; ERP , exposure response prevention; HRT , habit reversal training; PST , psychoeducation and supportive therapy; TS , Tourette syndrome; YGTSS , Yale Global Tic Severity Scale.

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

Yadegar M, Guo S, Ricketts EJ, Zinner SH. Assessment and management of tic disorders in pediatric primary care settings. Curr Dev Disord Rep. 2019;6(3):159–72. https://doi.org/10.1007/s40474-019-00168-8 .

Article   PubMed   PubMed Central   Google Scholar  

Nussey C, Pistrang N, Murphy T. How does psychoeducation help? A review of the effects of providing information about Tourette syndrome and attention-deficit/hyperactivity disorder. Child Care Health Dev. 2013;39(5):617–27. https://doi.org/10.1111/cch.12039 .

Article   CAS   PubMed   Google Scholar  

Chistol A LO. The role of family psychoeducation in the management of tics and tic-related impairment in grade school children. Abstracts of the ENCP Workshop for Junior Scientists. 2018.

Cen SS, Yu J, Wang Q, Deeb W, Wang KL, Shukla AW, et al. Multidisciplinary telemedicine care for Tourette syndrome: minireview. Front Neurol. 2020;11: 573576. https://doi.org/10.3389/fneur.2020.573576 .

Conte G, Valente F, Fioriello F, Cardona F. Rage attacks in Tourette syndrome and chronic tic disorder: a systematic review. Neurosci Biobehav Rev. 2020;119:21–36. https://doi.org/10.1016/j.neubiorev.2020.09.019 .

Article   PubMed   Google Scholar  

Cauberghe V, Van Wesenbeeck I, De Jans S, Hudders L, Ponnet K. How adolescents use social media to cope with feelings of loneliness and anxiety during COVID-19 lockdown. Cyberpsychol Behav Soc Netw. 2021;24(4):250–7. https://doi.org/10.1089/cyber.2020.0478 .

Heyman I, Liang H, Hedderly T. COVID-19 related increase in childhood tics and tic-like attacks. Arch Dis Child. 2021. https://doi.org/10.1136/archdischild-2021-321748 .

Perkins V, Coulson NS, Davies EB. Using online support communities for Tourette syndrome and tic disorders: online survey of users' experiences. J Med Internet Res. 2020;22(11):e18099. https://doi.org/10.2196/18099 .

•• Pringsheim T, Okun MS, Müller-Vahl K, Martino D, Jankovic J, Cavanna AE et al. Practice guideline recommendations summary: treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology. 2019;92(19):896-906. doi: https://doi.org/10.1212/WNL.0000000000007466 . Most recent AAN practice  guidelines for the treatment of TS

•• Andrén P, Jakubovski E, Murphy TL, Woitecki K, Tarnok Z, Zimmerman-Brenner S et al. European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part II: psychological interventions. Eur Child Adolesc Psychiatry. 2021. https://doi.org/10.1007/s00787-021-01845-z . Most recent European guidelines for the treatment of TS

Liu S, Li Y, Cui Y. Review of habit reversal training for tic disorders. Pediatr Investig. 2020;4(2):127–32. https://doi.org/10.1002/ped4.12190 .

Wu MS, McGuire JF. Psychoeducation about tic disorders and treatment. The clinician's guide to treatment and management of youth with Tourette syndrome and tic disorder. San Diego, CA, US: Elsevier Academic Press; 2018. p. 21–41.

•• Pringsheim T, Holler-Managan Y, Okun MS, Jankovic J, Piacentini J, Cavanna AE et al. Comprehensive systematic review summary: treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology. 2019;92(19):907-15. doi: https://doi.org/10.1212/WNL.0000000000007467 .  Recent systematic review that covers many details about efficacy and safety of treatments for TS

•• Steeves T, McKinlay BD, Gorman D, Billinghurst L, Day L, Carroll A, et al. Canadian guidelines for the evidence-based treatment of tic disorders: behavioural therapy, deep brain stimulation, and transcranial magnetic stimulation. Can J Psychiatry. 2012;57(3):144–51. https://doi.org/10.1177/070674371205700303 . Most  recent Canadian guidelines for the treatment of TS

Rizzo R, Pellico A, Silvestri PR, Chiarotti F, Cardona F. A randomized controlled trial comparing behavioral, educational, and pharmacological treatments in youths with chronic tic disorder or Tourette syndrome. Front Psychiatry. 2018;9:100. https://doi.org/10.3389/fpsyt.2018.00100 .

Kim KM, Bae E, Lee J, Park TW, Lim MH. A review of cognitive and behavioral interventions for tic disorder. Soa Chongsonyon Chongsin Uihak. 2021;32(2):51–62. https://doi.org/10.5765/jkacap.200042 .

Robertson MM. Gilles de la Tourette syndrome: the complexities of phenotype and treatment. Br J Hosp Med (Lond). 2011;72(2):100–7. https://doi.org/10.12968/hmed.2011.72.2.100 .

Article   Google Scholar  

Verdellen CW, Keijsers GP, Cath DC, Hoogduin CA. Exposure with response prevention versus habit reversal in Tourette’s syndrome: a controlled study. Behav Res Ther. 2004;42(5):501–11. https://doi.org/10.1016/S0005-7967(03)00154-2 .

Deckersbach T, Rauch S, Buhlmann U, Wilhelm S. Habit reversal versus supportive psychotherapy in Tourette’s disorder: a randomized controlled trial and predictors of treatment response. Behav Res Ther. 2006;44(8):1079–90. https://doi.org/10.1016/j.brat.2005.08.007 .

Wilhelm S, Deckersbach T, Coffey BJ, Bohne A, Peterson AL, Baer L. Habit reversal versus supportive psychotherapy for Tourette’s disorder: a randomized controlled trial. Am J Psychiatry. 2003;160(6):1175–7. https://doi.org/10.1176/appi.ajp.160.6.1175 .

O’Connor KP, Brault M, Robillard S, Loiselle J, Borgeat F, Stip E. Evaluation of a cognitive-behavioural program for the management of chronic tic and habit disorders. Behav Res Ther. 2001;39(6):667–81. https://doi.org/10.1016/s0005-7967(00)00048-6 .

Seragni G, Chiappedi M, Bettinardi B, Zibordi F, Colombo T, Reina C, et al. Habit reversal training in children and adolescents with chronic tic disorders: an Italian randomized, single-blind pilot study. Minerva Pediatr. 2018;70(1):5–11. https://doi.org/10.23736/S0026-4946.16.04344-9 .

Viefhaus P, Feldhausen M, Görtz-Dorten A, Volk H, Döpfner M, Woitecki K. Efficacy of habit reversal training in children with chronic tic disorders: a within-subject analysis. Behav Modif. 2020;44(1):114–36. https://doi.org/10.1177/0145445518796203 .

McGuire JF, Piacentini J, Scahill L, Woods DW, Villarreal R, Wilhelm S, et al. Bothersome tics in patients with chronic tic disorders: characteristics and individualized treatment response to behavior therapy. Behav Res Ther. 2015;70:56–63. https://doi.org/10.1016/j.brat.2015.05.006 .

McGinty HLDNA, Park JM, Storch EA. Living with tics: a cognitive-behavioral approach to improving coping and reducing tic severity in a young adult with Tourette disorder. Clin Case Stud. 2012;11(3):218–33.

Scahill L, Woods DW, Himle MB, Peterson AL, Wilhelm S, Piacentini JC, et al. Current controversies on the role of behavior therapy in Tourette syndrome. Mov Disord. 2013;28(9):1179–83. https://doi.org/10.1002/mds.25488 .

Petruo V, Bodmer B, Bluschke A, Münchau A, Roessner V, Beste C. Comprehensive behavioral intervention for tics reduces perception-action binding during inhibitory control in Gilles de la Tourette syndrome. Sci Rep. 2020;10(1):1174. https://doi.org/10.1038/s41598-020-58269-z .

Article   CAS   PubMed   PubMed Central   Google Scholar  

Woods DW, Piacentini JC, Scahill L, Peterson AL, Wilhelm S, Chang S, et al. Behavior therapy for tics in children: acute and long-term effects on psychiatric and psychosocial functioning. J Child Neurol. 2011;26(7):858–65. https://doi.org/10.1177/0883073810397046 .

Wilhelm S, Peterson AL, Piacentini J, Woods DW, Deckersbach T, Sukhodolsky DG, et al. Randomized trial of behavior therapy for adults with Tourette syndrome. Arch Gen Psychiatry. 2012;69(8):795–803. https://doi.org/10.1001/archgenpsychiatry.2011.1528 .

Piacentini J, Woods DW, Scahill L, Wilhelm S, Peterson AL, Chang S, et al. Behavior therapy for children with Tourette disorder: a randomized controlled trial. JAMA. 2010;303(19):1929–37. https://doi.org/10.1001/jama.2010.607 .

Espil F. A long term follow up to a randomized controlled trial of comprehensive behavioral intervention for tics: University of Wisconsin-Milwaukee; 2015.

McGuire JF, Ricketts EJ, Scahill L, Wilhelm S, Woods DW, Piacentini J, et al. Effect of behavior therapy for Tourette’s disorder on psychiatric symptoms and functioning in adults. Psychol Med. 2020;50(12):2046–56. https://doi.org/10.1017/S0033291719002150 .

Bennett SM, Capriotti M, Bauer C, Chang S, Keller AE, Walkup J, et al. Development and open trial of a psychosocial intervention for young children with chronic tics: the CBIT-JR Study. Behav Ther. 2020;51(4):659–69. https://doi.org/10.1016/j.beth.2019.10.004 .

Singer HS, McDermott S, Ferenc L, Specht M, Mahone EM. Efficacy of parent-delivered, home-based therapy for tics. Pediatr Neurol. 2020;106:17–23. https://doi.org/10.1016/j.pediatrneurol.2019.12.015 .

Yates R, Edwards K, King J, Luzon O, Evangeli M, Stark D, et al. Habit reversal training and educational group treatments for children with Tourette syndrome: a preliminary randomised controlled trial. Behav Res Ther. 2016;80:43–50. https://doi.org/10.1016/j.brat.2016.03.003 .

Dabrowski J, King J, Edwards K, Yates R, Heyman I, Zimmerman-Brenner S, et al. The long-term effects of group-based psychological interventions for children with Tourette syndrome: a randomized controlled trial. Behav Ther. 2018;49(3):331–43. https://doi.org/10.1016/j.beth.2017.10.005 .

Nissen JB, Kaergaard M, Laursen L, Parner E, Thomsen PH. Combined habit reversal training and exposure response prevention in a group setting compared to individual training: a randomized controlled clinical trial. Eur Child Adolesc Psychiatry. 2019;28(1):57–68. https://doi.org/10.1007/s00787-018-1187-z .

Heijerman-Holtgrefe AP, Verdellen CWJ, van de Griendt JMTM, Beljaars LPL, Kan KJ, Cath D, et al. Tackle your tics: pilot findings of a brief, intensive group-based exposure therapy program for children with tic disorders. Eur Child Adolesc Psychiatry. 2021;30(3):461–73. https://doi.org/10.1007/s00787-020-01532-5 .

Leclerc JB, O'Connor KP, J-Nolin G, Valois P, Lavoie ME. The effect of a new therapy for children with tics targeting underlying cognitive, behavioral, and physiological processes. Front Psychiatry. 2016;7:135. doi: https://doi.org/10.3389/fpsyt.2016.00135 .

O’Connor K, Lavoie M, Blanchet P, St-Pierre-Delorme M. Evaluation of a cognitive psychophysiological model for management of tic disorders: an open trial. Br J Psychiatry. 2016;209(1):76–83. https://doi.org/10.1192/bjp.bp.114.154518 .

Chen CW, Wang HS, Chang HJ, Hsueh CW. Effectiveness of a modified comprehensive behavioral intervention for tics for children and adolescents with Tourette’s syndrome: a randomized controlled trial. J Adv Nurs. 2020;76(3):903–15. https://doi.org/10.1111/jan.14279 .

Blount THRJ, Peterson AL. Intensive outpatient comprehensive behavioral intervention for tics: a clinical replication series. Cogn Behav Pract. 2017;25(1):156–67.

Blount TH, Lockhart AL, Garcia RV, Raj JJ, Peterson AL. Intensive outpatient comprehensive behavioral intervention for tics: a case series. World J Clin Cases. 2014;2(10):569–77. https://doi.org/10.12998/wjcc.v2.i10.569 .

Himle MB, Freitag M, Walther M, Franklin SA, Ely L, Woods DW. A randomized pilot trial comparing videoconference versus face-to-face delivery of behavior therapy for childhood tic disorders. Behav Res Ther. 2012;50(9):565–70. https://doi.org/10.1016/j.brat.2012.05.009 .

Ricketts EJ, Goetz AR, Capriotti MR, Bauer CC, Brei NG, Himle MB, et al. A randomized waitlist-controlled pilot trial of voice over Internet protocol-delivered behavior therapy for youth with chronic tic disorders. J Telemed Telecare. 2016;22(3):153–62. https://doi.org/10.1177/1357633X15593192 .

Andrén P, Aspvall K, Fernández de la Cruz L, Wiktor P, Romano S, Andersson E et al. Therapist-guided and parent-guided internet-delivered behaviour therapy for paediatric Tourette's disorder: a pilot randomised controlled trial with long-term follow-up. BMJ Open. 2019;9(2):e024685. doi: https://doi.org/10.1136/bmjopen-2018-024685 .

Conelea CA, Wellen BCM. Tic treatment goes tech: a review of TicHelper.com. Cogn Behav Pract. 2017;24(3):374–81. doi: https://doi.org/10.1016/j.cbpra.2017.01.003 .

Black JK, Koller JM, Black KJ. TicTimer software for measuring tic suppression. F1000Res. 2017;6:1560. doi: https://doi.org/10.12688/f1000research.12327.2 .

Hall CL, Davies EB, Andrén P, Murphy T, Bennett S, Brown BJ, et al. Investigating a therapist-guided, parent-assisted remote digital behavioural intervention for tics in children and adolescents-’Online Remote Behavioural Intervention for Tics’ (ORBIT) trial: protocol of an internal pilot study and single-blind randomised controlled trial. BMJ Open. 2019;9(1): e027583. https://doi.org/10.1136/bmjopen-2018-027583 .

Jakubovski E, Reichert C, Karch A, Buddensiek N, Breuer D, Müller-Vahl K. The ONLINE-TICS study protocol: a randomized observer-blind clinical trial to demonstrate the efficacy and safety of Internet-delivered behavioral treatment for adults with chronic tic disorders. Front Psychiatry. 2016;7:119. https://doi.org/10.3389/fpsyt.2016.00119 .

Hawksley J, Cavanna AE, Nagai Y. The role of the autonomic nervous system in Tourette syndrome. Front Neurosci. 2015;9:117. https://doi.org/10.3389/fnins.2015.00117 .

Nagai Y, Cavanna AE, Critchley HD, Stern JJ, Robertson MM, Joyce EM. Biofeedback treatment for Tourette syndrome: a preliminary randomized controlled trial. Cogn Behav Neurol. 2014;27(1):17–24. https://doi.org/10.1097/WNN.0000000000000019 .

Nagai Y, Cavanna A, Critchley HD. Influence of sympathetic autonomic arousal on tics: implications for a therapeutic behavioral intervention for Tourette syndrome. J Psychosom Res. 2009;67(6):599–605. https://doi.org/10.1016/j.jpsychores.2009.06.004 .

Sukhodolsky DG, Walsh C, Koller WN, Eilbott J, Rance M, Fulbright RK, et al. Randomized, sham-controlled trial of real-time functional magnetic resonance imaging neurofeedback for tics in adolescents with Tourette syndrome. Biol Psychiatry. 2020;87(12):1063–70. https://doi.org/10.1016/j.biopsych.2019.07.035 .

Seideman MF, Seideman TA. A review of the current treatment of Tourette syndrome.J Pediatr Pharmacol Ther. 2020;25(5):401-12. doi: https://doi.org/10.5863/1551-6776-25.5.401 . 

• Ueda K, Black KJ. A comprehensive review of tic disorders in children. J Clin Med. 2021;10(11). https://doi.org/10.3390/jcm10112479 . This paper gives a good overview of various different treatments for tic disorders in general

• Essoe JK, Grados MA, Singer HS, Myers NS, McGuire JF. Evidence-based treatment of Tourette’s disorder and chronic tic disorders. Expert Rev Neurother. 2019;19(11):1103–15. https://doi.org/10.1080/14737175.2019.1643236 . Similarly, this paper discusses multiple aspects of treatments for tic disorders

Goetz CG, Tanner CM, Wilson RS, Carroll VS, Como PG, Shannon KM. Clonidine and Gilles de la Tourette’s syndrome: double-blind study using objective rating methods. Ann Neurol. 1987;21(3):307–10. https://doi.org/10.1002/ana.410210313 .

Leckman JF, Hardin MT, Riddle MA, Stevenson J, Ort SI, Cohen DJ. Clonidine treatment of Gilles de la Tourette’s syndrome. Arch Gen Psychiatry. 1991;48(4):324–8. https://doi.org/10.1001/archpsyc.1991.01810280040006 .

Group TsSS. Treatment of ADHD in children with tics: a randomized controlled trial. Neurology. 2002;58(4):527–36. https://doi.org/10.1212/wnl.58.4.527 .

Du YS, Li HF, Vance A, Zhong YQ, Jiao FY, Wang HM, et al. Randomized double-blind multicentre placebo-controlled clinical trial of the clonidine adhesive patch for the treatment of tic disorders. Aust N Z J Psychiatry. 2008;42(9):807–13. https://doi.org/10.1080/00048670802277222 .

Song PP, Jiang L, Li XJ, Hong SQ, Li SZ, Hu Y. The efficacy and tolerability of the clonidine transdermal patch in the treatment for children with tic disorders: a prospective, open, single-group, self-controlled study. Front Neurol. 2017;8:32. https://doi.org/10.3389/fneur.2017.00032 .

Yang C, Kang B, Yu D, Zhao L, Zhang L. Effectiveness and safety of a clonidine adhesive patch for children with tic disorders: study in a real-world practice. Front Neurol. 2020;11:361. https://doi.org/10.3389/fneur.2020.00361 .

Kang H, Zhang YF, Jiao FY, Guo XY, Gao XM. Efficacy of clonidine transdermal patch for treatment of Tourette’s syndrome in children. Zhongguo Dang Dai Er Ke Za Zhi. 2009;11(7):537–9.

PubMed   Google Scholar  

Jiao F, Zhang X, Wang J. Clinical observation on treatment of Tourette syndrome in Chinese children by clonidine adhesive patch. Eur J Paediatr Neurol. 2016;20(1):80–4. https://doi.org/10.1016/j.ejpn.2015.10.002 .

Guo JM, Shi XX, Yang SW, Qian QF, Huang Y, Xie YQ, et al. Efficacy of clonidine transdermal patch in treatment of moderate to severe tic disorders in children. Zhongguo Dang Dai Er Ke Za Zhi. 2017;19(7):786–9.

Boon-yasidhi V, Kim YS, Scahill L. An open-label, prospective study of guanfacine in children with ADHD and tic disorders. J Med Assoc Thai. 2005;88(Suppl 8):S156–62.

Scahill L, Chappell PB, Kim YS, Schultz RT, Katsovich L, Shepherd E, et al. A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. Am J Psychiatry. 2001;158(7):1067–74. https://doi.org/10.1176/appi.ajp.158.7.1067 .

Cummings DD, Singer HS, Krieger M, Miller TL, Mahone EM. Neuropsychiatric effects of guanfacine in children with mild Tourette syndrome: a pilot study. Clin Neuropharmacol. 2002;25(6):325–32. https://doi.org/10.1097/00002826-200211000-00009 .

Murphy TK, Fernandez TV, Coffey BJ, Rahman O, Gavaletz A, Hanks CE, et al. Extended-release guanfacine does not show a large effect on tic severity in children with chronic tic disorders. J Child Adolesc Psychopharmacol. 2017;27(9):762–70. https://doi.org/10.1089/cap.2017.0024 .

Martínez-Granero MA, García-Pérez A, Montañes F. Levetiracetam as an alternative therapy for Tourette syndrome. Neuropsychiatr Dis Treat. 2010;6:309–16. https://doi.org/10.2147/ndt.s6371 .

Jankovic J, Jimenez-Shahed J, Brown LW. A randomised, double-blind, placebo-controlled study of topiramate in the treatment of Tourette syndrome. J Neurol Neurosurg Psychiatry. 2010;81(1):70–3. https://doi.org/10.1136/jnnp.2009.185348 .

Kuo SH, Jimenez-Shahed J. Topiramate in treatment of Tourette syndrome. Clin Neuropharmacol. 2010;33(1):32–4. https://doi.org/10.1097/WNF.0b013e3181c295c1 .

Awaad YMA, Minarik S. Long-term use of levetiracetam to treat tics in children and adolescents with Tourette syndrome. J Ped Neurol. 2007;5(3):209–14.

Smith-Hicks CL, Bridges DD, Paynter NP, Singer HS. A double blind randomized placebo control trial of levetiracetam in Tourette syndrome. Mov Disord. 2007;22(12):1764–70. https://doi.org/10.1002/mds.21615 .

Hedderick EF, Morris CM, Singer HS. Double-blind, crossover study of clonidine and levetiracetam in Tourette syndrome. Pediatr Neurol. 2009;40(6):420-5. doi: https://doi.org/10.1016/j.pediatrneurol.2008.12.014 . 

• Quezada J, Coffman KA. Current approaches and new developments in the pharmacological management of Tourette syndrome. CNS Drugs. 2018;32(1):33–45. https://doi.org/10.1007/s40263-017-0486-0 . A comprehensive overview of the  pharmacotherapies used to treat TS

Singer HS, Wendlandt J, Krieger M, Giuliano J. Baclofen treatment in Tourette syndrome: a double-blind, placebo-controlled, crossover trial. Neurology. 2001;56(5):599–604. https://doi.org/10.1212/wnl.56.5.599 .

Deeb W, Malaty IA, Mathews CA. Tourette disorder and other tic disorders. Handb Clin Neurol. 2019;165:123–53. https://doi.org/10.1016/B978-0-444-64012-3.00008-3 .

Gulisano M, Calì PV, Cavanna AE, Eddy C, Rickards H, Rizzo R. Cardiovascular safety of aripiprazole and pimozide in young patients with Tourette syndrome. Neurol Sci. 2011;32(6):1213–7. https://doi.org/10.1007/s10072-011-0678-1 .

Yang C, Yi Q, Zhang L, Cui H, Mao J. Safety of aripiprazole for tics in children and adolescents: a systematic review and meta-analysis. Medicine (Baltimore). 2019;98(22): e15816. https://doi.org/10.1097/MD.0000000000015816 .

Yang CS, Huang H, Zhang LL, Zhu CR, Guo Q. Aripiprazole for the treatment of tic disorders in children: a systematic review and meta-analysis. BMC Psychiatry. 2015;15:179. https://doi.org/10.1186/s12888-015-0504-z .

Tao D, Zhong T, Ma S, Li J, Li X. Randomized controlled clinical trial comparing the efficacy and tolerability of aripiprazole and sodium valproate in the treatment of Tourette syndrome. Ann Gen Psychiatry. 2019;18:24. https://doi.org/10.1186/s12991-019-0245-3 .

Budman CL. The role of atypical antipsychotics for treatment of Tourette’s syndrome: an overview. Drugs. 2014;74(11):1177–93. https://doi.org/10.1007/s40265-014-0254-0 .

Gilbert DL, Budman CL, Singer HS, Kurlan R, Chipkin RE. A D1 receptor antagonist, ecopipam, for treatment of tics in Tourette syndrome. Clin Neuropharmacol. 2014;37(1):26–30. https://doi.org/10.1097/WNF.0000000000000017 .

Gilbert DL, Murphy TK, Jankovic J, Budman CL, Black KJ, Kurlan RM, et al. Ecopipam, a D1 receptor antagonist, for treatment of Tourette syndrome in children: a randomized, placebo-controlled crossover study. Mov Disord. 2018;33(8):1272–80. https://doi.org/10.1002/mds.27457 .

Jankovic J, Glaze DG, Frost JD. Effect of tetrabenazine on tics and sleep of Gilles de la Tourette’s syndrome. Neurology. 1984;34(5):688–92. https://doi.org/10.1212/wnl.34.5.688 .

Kenney C, Hunter C, Jankovic J. Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders. Mov Disord. 2007;22(2):193–7. https://doi.org/10.1002/mds.21222 .

Jankovic J, Jimenez-Shahed J, Budman C, Coffey B, Murphy T, Shprecher D, et al. Deutetrabenazine in tics associated with Tourette syndrome. Tremor Other Hyperkinet Mov (N Y). 2016;6:422. https://doi.org/10.7916/D8M32W3H .

Farber RH, Angelov A, Kim K, Carmack T, Thai-Cuarto D, Roberts E. Clinical development of valbenazine for tics associated with Tourette syndrome. Expert Rev Neurother. 2021;21(4):393–404. https://doi.org/10.1080/14737175.2021.1898948 .

Szejko N, Jakubovski E, Muller-Vahl K. Possible role of the endocannabinoid system in Tourette syndrome. Recent Advances in Cannabinoid Research. IntechOpen; 2018.

Müller-Vahl KR, Schneider U, Koblenz A, Jöbges M, Kolbe H, Daldrup T, et al. Treatment of Tourette’s syndrome with Delta 9-tetrahydrocannabinol (THC): a randomized crossover trial. Pharmacopsychiatry. 2002;35(2):57–61. https://doi.org/10.1055/s-2002-25028 .

Müller-Vahl KR, Schneider U, Prevedel H, Theloe K, Kolbe H, Daldrup T, et al. Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial. J Clin Psychiatry. 2003;64(4):459–65. https://doi.org/10.4088/jcp.v64n0417 .

Curtis A, Clarke CE, Rickards HE. Cannabinoids for Tourette's syndrome. Cochrane Database Syst Rev. 2009(4):CD006565. doi: https://doi.org/10.1002/14651858.CD006565.pub2 .

Artukoglu BB, Bloch MH. The potential of cannabinoid-based treatments in Tourette syndrome. CNS Drugs. 2019;33(5):417–30. https://doi.org/10.1007/s40263-019-00627-1 .

Milosev LM, Psathakis N, Szejko N, Jakubovski E, Müller-Vahl KR. Treatment of Gilles de la Tourette syndrome with cannabis-based medicine: results from a retrospective analysis and online survey. Cannabis Cannabinoid Res. 2019;4(4):265–74. https://doi.org/10.1089/can.2018.0050 .

Jakubovski E, Pisarenko A, Fremer C, Haas M, May M, Schumacher C, et al. The CANNA-TICS study protocol: a randomized multi-center double-blind placebo controlled trial to demonstrate the efficacy and safety of nabiximols in the treatment of adults with chronic tic disorders. Front Psychiatry. 2020;11: 575826. https://doi.org/10.3389/fpsyt.2020.575826 .

Mueller-Vahl K. ABX-1431, a first-in-class endocannabinoid modulator, improves tics in adult patients with Tourette syndrome. Neurology. 2018;90:e2182–3.

Müller-Vahl KR, Fremer C, Beals C, Ivkovic J, Loft H, Schindler C. Monoacylglycerol lipase inhibition in Tourette syndrome: a 12-week, randomized, controlled study. Mov Disord. 2021;36(10):2413–8. https://doi.org/10.1002/mds.28681 .

Bloch MH, Landeros-Weisenberger A, Johnson JA, Leckman JF. A phase-2 pilot study of a therapeutic combination of Δ. J Neuropsychiatry Clin Neurosci. 2021;33(4):328–36. https://doi.org/10.1176/appi.neuropsych.19080178 .

Aguirregomozcorta M, Pagonabarraga J, Diaz-Manera J, Pascual-Sedano B, Gironell A, Kulisevsky J. Efficacy of botulinum toxin in severe Tourette syndrome with dystonic tics involving the neck. Parkinsonism Relat Disord. 2008;14(5):443–5. https://doi.org/10.1016/j.parkreldis.2007.10.007 .

Trimble MR, Whurr R, Brookes G, Robertson MM. Vocal tics in Gilles de la Tourette syndrome treated with botulinum toxin injections. Mov Disord. 1998;13(3):617–9. https://doi.org/10.1002/mds.870130348 .

Scott BL, Jankovic J, Donovan DT. Botulinum toxin injection into vocal cord in the treatment of malignant coprolalia associated with Tourette’s syndrome. Mov Disord. 1996;11(4):431–3. https://doi.org/10.1002/mds.870110413 .

Salloway S, Stewart CF, Israeli L, Morales X, Rasmussen S, Blitzer A, et al. Botulinum toxin for refractory vocal tics. Mov Disord. 1996;11(6):746–8. https://doi.org/10.1002/mds.870110627 .

Jankovic J. Botulinum toxin in the treatment of dystonic tics. Mov Disord. 1994;9(3):347–9. https://doi.org/10.1002/mds.870090315 .

Kwak CH, Hanna PA, Jankovic J. Botulinum toxin in the treatment of tics. Arch Neurol. 2000;57(8):1190–3. https://doi.org/10.1001/archneur.57.8.1190 .

Porta M, Maggioni G, Ottaviani F, Schindler A. Treatment of phonic tics in patients with Tourette’s syndrome using botulinum toxin type A. Neurol Sci. 2004;24(6):420–3. https://doi.org/10.1007/s10072-003-0201-4 .

Rath JJ, Tavy DL, Wertenbroek AA, van Woerkom TC, de Bruijn SF. Botulinum toxin type A in simple motor tics: short-term and long-term treatment-effects. Parkinsonism Relat Disord. 2010;16(7):478–81. https://doi.org/10.1016/j.parkreldis.2009.11.011 .

Marras C, Andrews D, Sime E, Lang AE. Botulinum toxin for simple motor tics: a randomized, double-blind, controlled clinical trial. Neurology. 2001;56(5):605–10. https://doi.org/10.1212/wnl.56.5.605 .

Pandey S, Srivanitchapoom P, Kirubakaran R, Berman BD. Botulinum toxin for motor and phonic tics in Tourette's syndrome. Cochrane Database Syst Rev. 2018;1:CD012285. doi: https://doi.org/10.1002/14651858.CD012285.pub2 .

Patel H, Nguyen K, Lehman E, Mainali G, Duda L, Byler D, et al. Use of complementary and alternative medicine in children with Tourette syndrome. J Child Neurol. 2020;35(8):512–6. https://doi.org/10.1177/0883073820913670 .

Qi H, Liu R, Zheng W, Zhang L, Ungvari GS, Ng CH et al. Efficacy and safety of traditional Chinese medicine for Tourette's syndrome: a meta-analysis of randomized controlled trials. Asian J Psychiatr. 2020;47:101853. https://doi.org/10.1016/j.ajp.2019.101853 . 

• Wang N, Qin DD, Xie YH, Wu XC, Wang DY, Hang-Yang et al. Traditional Chinese medicine strategy for patients with Tourette syndrome based on clinical efficacy and safety: a meta-analysis of 47 randomized controlled trials. Biomed Res Int. 2021;2021:6630598. https://doi.org/10.1155/2021/6630598 . Overview of various TCM approaches for the treatment of TS

Lv J, Zhu Q, Hao Y. The treatment of Choudongning capsule in children with Tourette’s syndrome: a double blind and double simulation clinical study (in Chinese). Global Tradit Chin Med. 2013;6:85–6.

Google Scholar  

Yang N, Ma R, Hu SY, Liu H, Yan HM, Xiang XX, et al. Efficacy and safety of Choudongning capsule (CDN)in children with Tourette’s syndrome of spleen deficiency and phlegm accumulation. Zhongguo Zhong Yao Za Zhi. 2016;41(16):3100–6. https://doi.org/10.4268/cjcmm20161627 .

Zheng Y, Zhang ZJ, Han XM, Ding Y, Chen YY, Wang XF, et al. A proprietary herbal medicine (5-Ling Granule) for Tourette syndrome: a randomized controlled trial. J Child Psychol Psychiatry. 2016;57(1):74–83. https://doi.org/10.1111/jcpp.12432 .

Hu S, Ma R, TIan T. Phase III clinical research of Changma Xifeng tablets in treating multiple tics with liver wind and sputum stirring internally (in Chinese). Drugs Clin. 2014;29(9):1044–9.

Sun Q. Clinical observation on Changma Xifeng tablets in the treatment of 36 cases of Tourette’s syndrome. Management of Health Standards in China. 2016;131(2):1674–93.

Lu C, Wu LQ, Hao H, Kimberly Leow X, Xu FW, Li PP, et al. Clinical efficacy and safety of acupuncture treatment of TIC disorder in children: a systematic review and meta-analysis of 22 randomized controlled trials. Complement Ther Med. 2021;59: 102734. https://doi.org/10.1016/j.ctim.2021.102734 .

Yu J, Ye Y, Liu J, Wang Y, Peng W, Liu Z. Acupuncture for Tourette syndrome: a systematic review. Evid Based Complement Alternat Med. 2016;2016:1834646. https://doi.org/10.1155/2016/1834646 .

Chung S, Noh B, Lee C, Hwang M, Kang M, Kwon S, et al. Acupuncture for Tourette syndrome: a systematic review and meta-analysis. Eur J Integ Med. 2016;8:809–16.

Ding L, Yang Z, Liu G, Ran N, Yi M, Li H, et al. Safety and efficacy of taurine as an add-on treatment for tics in youngsters. Eur J Neurol. 2020;27(3):490–7. https://doi.org/10.1111/ene.14107 .

Bond M, Moll N, Rosello A, Bond R, Schnell J, Burger B, et al. Vitamin D levels in children and adolescents with chronic tic disorders: a multicentre study. Eur Child Adolesc Psychiatry. 2021. https://doi.org/10.1007/s00787-021-01757-y .

Li HH, Shan L, Wang B, Du L, Xu ZD, Jia FY. Serum 25-hyroxyvitamin D levels and tic severity in Chinese children with tic disorders. Psychiatry Res. 2018;267:80–4. https://doi.org/10.1016/j.psychres.2018.05.066 .

Li HH, Xu ZD, Wang B, Feng JY, Dong HY, Jia FY. Clinical improvement following vitamin D3 supplementation in children with chronic tic disorders. Neuropsychiatr Dis Treat. 2019;15:2443–50. https://doi.org/10.2147/NDT.S212322 .

Murakami J, Tachibana Y, Akiyama S, Kato T, Taniguchi A, Nakajima Y, et al. Oral splint ameliorates tic symptoms in patients with Tourette syndrome. Mov Disord. 2019;34(10):1577–8. https://doi.org/10.1002/mds.27819 .

Liu YW, Liong MT, Chung YE, Huang HY, Peng WS, Cheng YF et al. Effects of nutrients. 2019;11(4). doi: https://doi.org/10.3390/nu11040820 .

Zhao H, Shi Y, Luo X, Peng L, Yang Y, Zou L. The effect of fecal microbiota transplantation on a child with Tourette syndrome. Case Rep Med. 2017;2017:6165239. https://doi.org/10.1155/2017/6165239 .

Zhao HJ, Luo X, Shi YC, Li JF, Pan F, Ren RR, et al. The efficacy of fecal microbiota transplantation for children with Tourette syndrome: a preliminary study. Front Psychiatry. 2020;11: 554441. https://doi.org/10.3389/fpsyt.2020.554441 .

McGuire JF, Ginder N, Ramsey K, Essoe JK, Ricketts EJ, McCracken JT, et al. Optimizing behavior therapy for youth with Tourette’s disorder. Neuropsychopharmacology. 2020;45(12):2114–9. https://doi.org/10.1038/s41386-020-0762-4 .

Fletcher J, Martino D, Pringsheim T. Novel pharmacological approaches for Tourette syndrome. Curr Dev Disord Rep. 2020;7:270–6.

Chae JH, Nahas Z, Wassermann E, Li X, Sethuraman G, Gilbert D, et al. A pilot safety study of repetitive transcranial magnetic stimulation (rTMS) in Tourette’s syndrome. Cogn Behav Neurol. 2004;17(2):109–17. https://doi.org/10.1097/01.wnn.0000116253.78804.3a .

Kahl CK, Kirton A, Pringsheim T, Croarkin PE, Zewdie E, Swansburg R, et al. Bilateral transcranial magnetic stimulation of the supplementary motor area in children with Tourette syndrome. Dev Med Child Neurol. 2021;63(7):808–15. https://doi.org/10.1111/dmcn.14828 .

Kwon HJ, Lim WS, Lim MH, Lee SJ, Hyun JK, Chae JH, et al. 1-Hz low frequency repetitive transcranial magnetic stimulation in children with Tourette’s syndrome. Neurosci Lett. 2011;492(1):1–4. https://doi.org/10.1016/j.neulet.2011.01.007 .

Landeros-Weisenberger A, Mantovani A, Motlagh MG, de Alvarenga PG, Katsovich L, Leckman JF, et al. Randomized sham controlled double-blind trial of repetitive transcranial magnetic stimulation for adults with severe Tourette syndrome. Brain Stimul. 2015;8(3):574–81. https://doi.org/10.1016/j.brs.2014.11.015 .

Le K, Liu L, Sun M, Hu L, Xiao N. Transcranial magnetic stimulation at 1 Hertz improves clinical symptoms in children with Tourette syndrome for at least 6 months. J Clin Neurosci. 2013;20(2):257–62. https://doi.org/10.1016/j.jocn.2012.01.049 .

Mantovani A, Lisanby SH, Pieraccini F, Ulivelli M, Castrogiovanni P, Rossi S. Repetitive transcranial magnetic stimulation (rTMS) in the treatment of obsessive-compulsive disorder (OCD) and Tourette’s syndrome (TS). Int J Neuropsychopharmacol. 2006;9(1):95–100. https://doi.org/10.1017/S1461145705005729 .

Mantovani A, Leckman JF, Grantz H, King RA, Sporn AL, Lisanby SH. Repetitive transcranial magnetic stimulation of the supplementary motor area in the treatment of Tourette syndrome: report of two cases. Clin Neurophysiol. 2007;118(10):2314–5. https://doi.org/10.1016/j.clinph.2007.07.011 .

Münchau A, Bloem BR, Thilo KV, Trimble MR, Rothwell JC, Robertson MM. Repetitive transcranial magnetic stimulation for Tourette syndrome. Neurology. 2002;59(11):1789–91. https://doi.org/10.1212/01.wnl.0000036615.25044.50 .

Orth M, Kirby R, Richardson MP, Snijders AH, Rothwell JC, Trimble MR, et al. Subthreshold rTMS over pre-motor cortex has no effect on tics in patients with Gilles de la Tourette syndrome. Clin Neurophysiol. 2005;116(4):764–8. https://doi.org/10.1016/j.clinph.2004.10.003 .

Wu SW, Maloney T, Gilbert DL, Dixon SG, Horn PS, Huddleston DA, et al. Functional MRI-navigated repetitive transcranial magnetic stimulation over supplementary motor area in chronic tic disorders. Brain Stimul. 2014;7(2):212–8. https://doi.org/10.1016/j.brs.2013.10.005 .

Fu M, Wei H, Meng X, Chen H, Shang B, Chen F, et al. Effects of low-frequency repetitive transcranial magnetic stimulation of the bilateral parietal cortex in patients with Tourette syndrome. Front Neurol. 2021;12: 602830. https://doi.org/10.3389/fneur.2021.602830 .

Motiwala F, Sangroula D, Ashraf S, Virk I. Repetitive transcranial magnetic stimulation for tic disorders. Curr Psych. 2018;17(6):24–5.

Hsu CW, Wang LJ, Lin PY. Efficacy of repetitive transcranial magnetic stimulation for Tourette syndrome: a systematic review and meta-analysis. Brain Stimul. 2018;11(5):1110–8. https://doi.org/10.1016/j.brs.2018.06.002 .

Bloch Y, Arad S, Levkovitz Y. Deep TMS add-on treatment for intractable Tourette syndrome: a feasibility study. World J Biol Psychiatry. 2016;17(7):557–61. https://doi.org/10.3109/15622975.2014.964767 .

Singh S, Kumar S, Kumar N, Verma R. Low-frequency repetitive transcranial magnetic stimulation for treatment of tourette syndrome: a naturalistic study with 3 months of follow-up. Indian J Psychol Med. 2018;40(5):482–6. https://doi.org/10.4103/IJPSYM.IJPSYM_332_17 .

Eapen V, Baker R, Walter A, Raghupathy V, Wehrman JJ, Sowman PF. The role of transcranial direct current stimulation (tDCS) in Tourette syndrome: a review and preliminary findings. Brain Sci. 2017;7(12). doi: https://doi.org/10.3390/brainsci7120161 .

Dyke K, Jackson GM, Nixon E, Jackson SR. Effects of single-session cathodal transcranial direct current stimulation on tic symptoms in Tourette’s syndrome. Exp Brain Res. 2019;237(11):2853–63. https://doi.org/10.1007/s00221-019-05637-5 .

Martino D, Nosratmishekarlou E, Jasaui Y, Medina A, Vicario C, Nitsche M et al. Transcranial direct current stimulation over the supplementary motor area in Tourette syndrome: preliminary findings of a randomized controlled trial. Mov Disord. 2020;35.

Mrakic-Sposta S, Marceglia S, Mameli F, Dilena R, Tadini L, Priori A. Transcranial direct current stimulation in two patients with Tourette syndrome. Mov Disord. 2008;23(15):2259–61. https://doi.org/10.1002/mds.22292 .

Tajadini S, Mohammadi N, Tahamtan M, Nami M. Cathodal transcranial direct current stimulation to ameliorate the frequency and severity of motor tics: a case study of Tourette syndrome. JAMSAT. 2018;4(1):21–6.

Carvalho S, Gonçalves Ó, Soares JM, Sampaio A, Macedo F, Fregni F, et al. Sustained effects of a neural-based intervention in a refractory case of Tourette syndrome. Brain Stimul. 2015;8(3):657–9. https://doi.org/10.1016/j.brs.2014.12.008 .

Behler N, Leitner B, Mezger E, Weidinger E, Musil R, Blum B, et al. Cathodal tDCS over motor cortex does not improve Tourette syndrome: lessons learned from a case series. Front Behav Neurosci. 2018;12:194. https://doi.org/10.3389/fnbeh.2018.00194 .

Diamond A, Kenney C, Jankovic J. Effect of vagal nerve stimulation in a case of Tourette’s syndrome and complex partial epilepsy. Mov Disord. 2006;21(8):1273–5. https://doi.org/10.1002/mds.20949 .

Sperling W, Reulbach U, Maihöfner C, Kornhuber J, Bleich S. Vagus nerve stimulation in a patient with Gilles de la Tourette syndrome and major depression. Pharmacopsychiatry. 2008;41(3):117–8. https://doi.org/10.1055/s-2008-1062698 .

Caffery C. Transcutaneous vagal nerve stimulation & breathing exercises reduce motor and vocal tics in eleven-year-old male. Front Neurol. 2018.

Münchau A, Colzato LS, AghajaniAfjedi A, Beste C. A neural noise account of Gilles de la Tourette syndrome. Neuroimage Clin. 2021;30: 102654. https://doi.org/10.1016/j.nicl.2021.102654 .

Morera Maiquez B, Sigurdsson HP, Dyke K, Clarke E, McGrath P, Pasche M, et al. Entraining movement-related brain oscillations to suppress tics in Tourette syndrome. Curr Biol. 2020;30(12):2334-42.e3. https://doi.org/10.1016/j.cub.2020.04.044 .

Morera Maiquez B, Jackson GM, Jackson SR. Examining the neural antecedents of tics in Tourette syndrome using electroencephalography. J Neuropsychol. 2021. https://doi.org/10.1111/jnp.12245 .

Qiao J, Weng S, Wang P, Long J, Wang Z. Normalization of intrinsic neural circuits governing Tourette’s syndrome using cranial electrotherapy stimulation. IEEE Trans Biomed Eng. 2015;62(5):1272–80. https://doi.org/10.1109/TBME.2014.2385151 .

Deeb W, Leentjens AFG, Mogilner AY, Servello D, Meng F, Zhang J, et al. Deep brain stimulation lead removal in Tourette syndrome. Parkinsonism Relat Disord. 2020;77:89–93. https://doi.org/10.1016/j.parkreldis.2020.06.025 .

Schrock LE, Mink JW, Woods DW, Porta M, Servello D, Visser-Vandewalle V et al. Tourette syndrome deep brain stimulation: a review and updated recommendations. Mov Disord. 2015;30(4):448-71. doi: https://doi.org/10.1002/mds.26094 . 

•• Martino D, Deeb W, Jimenez-Shahed J, Malaty I, Pringsheim TM, Fasano A, et al. The 5 pillars in Tourette syndrome deep brain stimulation patient selection: present and future. Neurology. 2021;96(14):664–76. https://doi.org/10.1212/WNL.0000000000011704 . Important guideline updates for how to select patients with TS for DBS treatment

Deeb W, Malaty I. Deep brain stimulation for Tourette syndrome: potential role in the pediatric population. J Child Neurol. 2020;35(2):155–65. https://doi.org/10.1177/0883073819872620 .

Hauseux PA, Cyprien F, Cif L, Gonzalez V, Boulenger JP, Coubes P et al. Long-term follow-up of pallidal deep brain stimulation in teenagers with refractory Tourette syndrome and comorbid psychiatric disorders: about three cases. Eur J Paediatr Neurol. 2017;21(1):214–7. doi: https://doi.org/10.1016/j.ejpn.2016.06.005 . 

• Coulombe MA, Elkaim LM, Alotaibi NM, Gorman DA, Weil AG, Fallah A, et al. Deep brain stimulation for Gilles de la Tourette syndrome in children and youth: a meta-analysis with individual participant data. J Neurosurg Pediatr. 2018;23(2):236–46. https://doi.org/10.3171/2018.7.PEDS18300 . Good overview of the safety and efficacy of DBS for TS

Casagrande SCB, Cury RG, Alho EJL, Fonoff ET. Deep brain stimulation in Tourette’s syndrome: evidence to date. Neuropsychiatr Dis Treat. 2019;15:1061–75. https://doi.org/10.2147/NDT.S139368 .

Deeb W, Rossi PJ, Porta M, Visser-Vandewalle V, Servello D, Silburn P, et al. The International Deep Brain Stimulation Registry and Database for Gilles de la Tourette Syndrome: how does it work? Front Neurosci. 2016;10:170. https://doi.org/10.3389/fnins.2016.00170 .

Akbarian-Tefaghi L, Zrinzo L, Foltynie T. The use of deep brain stimulation in Tourette syndrome. Brain Sci. 2016;6(3). doi: https://doi.org/10.3390/brainsci6030035 .

Xu W, Zhang C, Deeb W, Patel B, Wu Y, Voon V, et al. Deep brain stimulation for Tourette’s syndrome. Transl Neurodegener. 2020;9:4. https://doi.org/10.1186/s40035-020-0183-7 .

Servello D, Galbiati TF, Balestrino R, Iess G, Zekaj E, Michele S et al. Deep brain stimulation for Gilles de la Tourette syndrome: toward limbic targets. Brain Sci. 2020;10(5). doi: https://doi.org/10.3390/brainsci10050301 .

Baldermann JC, Schüller T, Huys D, Becker I, Timmermann L, Jessen F, et al. Deep brain stimulation for Tourette-syndrome: a systematic review and meta-analysis. Brain Stimul. 2016;9(2):296–304. https://doi.org/10.1016/j.brs.2015.11.005 .

Huys D, Bartsch C, Koester P, Lenartz D, Maarouf M, Daumann J, et al. Motor improvement and emotional stabilization in patients with Tourette syndrome after deep brain stimulation of the ventral anterior and ventrolateral motor part of the thalamus. Biol Psychiatry. 2016;79(5):392–401. https://doi.org/10.1016/j.biopsych.2014.05.014 .

Rossi PJ, Opri E, Shute JB, Molina R, Bowers D, Ward H, et al. Scheduled, intermittent stimulation of the thalamus reduces tics in Tourette syndrome. Parkinsonism Relat Disord. 2016;29:35–41. https://doi.org/10.1016/j.parkreldis.2016.05.033 .

Schoenberg MR, Maddux BN, Riley DE, Whitney CM, Ogrocki PK, Gould D, et al. Five-months-postoperative neuropsychological outcome from a pilot prospective randomized clinical trial of thalamic deep brain stimulation for Tourette syndrome. Neuromodulation. 2015;18(2):97–104. https://doi.org/10.1111/ner.12233 .

Servello D, Zekaj E, Saleh C, Lange N, Porta M. Deep brain stimulation in Gilles de la Tourette syndrome: what does the future hold? A cohort of 48 patients. Neurosurgery. 2016;78(1):91–100. https://doi.org/10.1227/NEU.0000000000001004 .

Okun MS, Foote KD, Wu SS, Ward HE, Bowers D, Rodriguez RL, et al. A trial of scheduled deep brain stimulation for Tourette syndrome: moving away from continuous deep brain stimulation paradigms. JAMA Neurol. 2013;70(1):85–94. https://doi.org/10.1001/jamaneurol.2013.580 .

Ackermans L, Duits A, van der Linden C, Tijssen M, Schruers K, Temel Y, et al. Double-blind clinical trial of thalamic stimulation in patients with Tourette syndrome. Brain. 2011;134(Pt 3):832–44. https://doi.org/10.1093/brain/awq380 .

Kefalopoulou Z, Zrinzo L, Jahanshahi M, Candelario J, Milabo C, Beigi M, et al. Bilateral globus pallidus stimulation for severe Tourette’s syndrome: a double-blind, randomised crossover trial. Lancet Neurol. 2015;14(6):595–605. https://doi.org/10.1016/S1474-4422(15)00008-3 .

Welter ML, Houeto JL, Thobois S, Bataille B, Guenot M, Worbe Y, et al. Anterior pallidal deep brain stimulation for Tourette’s syndrome: a randomised, double-blind, controlled trial. Lancet Neurol. 2017;16(8):610–9. https://doi.org/10.1016/S1474-4422(17)30160-6 .

Baldermann JC, Kuhn J, Schüller T, Kohl S, Andrade P, Schleyken S, et al. Thalamic deep brain stimulation for Tourette syndrome: a naturalistic trial with brief randomized, double-blinded sham-controlled periods. Brain Stimul. 2021;14(5):1059–67. https://doi.org/10.1016/j.brs.2021.07.003 .

Welter ML, Mallet L, Houeto JL, Karachi C, Czernecki V, Cornu P, et al. Internal pallidal and thalamic stimulation in patients with Tourette syndrome. Arch Neurol. 2008;65(7):952–7. https://doi.org/10.1001/archneur.65.7.952 .

Marceglia S, Rosa M, Servello D, Porta M, Barbieri S, Moro E et al. Adaptive deep brain stimulation (aDBS) for Tourette syndrome. Brain Sci. 2017;8(1). doi: https://doi.org/10.3390/brainsci8010004 .

Neumann WJ, Huebl J, Brücke C, Lofredi R, Horn A, Saryyeva A, et al. Pallidal and thalamic neural oscillatory patterns in Tourette’s syndrome. Ann Neurol. 2018;84(4):505–14. https://doi.org/10.1002/ana.25311 .

Molina R, Okun MS, Shute JB, Opri E, Rossi PJ, Martinez-Ramirez D, et al. Report of a patient undergoing chronic responsive deep brain stimulation for Tourette syndrome: proof of concept. J Neurosurg. 2018;129(2):308–14. https://doi.org/10.3171/2017.6.JNS17626 .

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Frey, J., Malaty, I.A. Tourette Syndrome Treatment Updates: a Review and Discussion of the Current and Upcoming Literature. Curr Neurol Neurosci Rep 22 , 123–142 (2022). https://doi.org/10.1007/s11910-022-01177-8

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  • Published: 07 September 2023

Cell-therapy for Parkinson’s disease: a systematic review and meta-analysis

  • Fang Wang 1   na1 ,
  • Zhengwu Sun 2   na1 ,
  • Daoyong Peng 1   na1 ,
  • Shikha Gianchandani 3 ,
  • Weidong Le 4 ,
  • Johannes Boltze 3 &
  • Shen Li   ORCID: orcid.org/0000-0001-6779-9812 5 , 6  

Journal of Translational Medicine volume  21 , Article number:  601 ( 2023 ) Cite this article

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Cell-based strategies focusing on replacement or protection of dopaminergic neurons have been considered as a potential approach to treat Parkinson’s disease (PD) for decades. However, despite promising preclinical results, clinical trials on cell-therapy for PD reported mixed outcomes and a thorough synthesis of these findings is lacking. We performed a systematic review and meta-analysis to evaluate cell-therapy for PD patients.

We systematically identified all clinical trials investigating cell- or tissue-based therapies for PD published before July 2023. Out of those, studies reporting transplantation of homogenous cells (containing one cell type) were included in meta-analysis. The mean difference or standardized mean difference in quantitative neurological scale scores before and after cell-therapy was analyzed to evaluate treatment effects.

The systematic literature search revealed 106 articles. Eleven studies reporting data from 11 independent trials (210 patients) were eligible for meta-analysis. Disease severity and motor function evaluation indicated beneficial effects of homogenous cell-therapy in the ‘off’ state at 3-, 6-, 12-, or 24-month follow-ups, and for motor function even after 36 months. Most of the patients were levodopa responders (61.6–100% in different follow-ups). Cell-therapy was also effective in improving the daily living activities in the ‘off’ state of PD patients. Cells from diverse sources were used and multiple transplantation modes were applied. Autografts did not improve functional outcomes, while allografts exhibited beneficial effects. Encouragingly, both transplantation into basal ganglia and to areas outside the basal ganglia were effective to reduce disease severity. Some trials reported adverse events potentially related to the surgical procedure. One confirmed and four possible cases of graft-induced dyskinesia were reported in two trials included in this meta-analysis.

Conclusions

This meta-analysis provides preliminary evidence for the beneficial effects of homogenous cell-therapy for PD, potentially to the levodopa responders. Allogeneic cells were superior to autologous cells, and the effective transplantation sites are not limited to the basal ganglia.

PROSPERO registration number : CRD42022369760

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disease, and no curative therapy is currently available [ 1 ]. Thus, alternative solutions are urgently needed. PD has long been considered to be among the most promising target diseases for cell replacement therapy due to the specific loss of dopaminergic neurons in the substantia nigra [ 2 ], and cell-based therapies for PD has been explored clinically during the past decades. Initial studies mostly focused on transplantation of tissues such as embryonic mesencephalic tissue, adrenal medulla tissue, carotid body tissue, and sympathetic ganglion tissue. A meta-analysis on tissue transplantation demonstrated improved functional outcome [ 3 ]. However, tissue transplantation has several shortcomings including severe graft-induced dyskinesia (GID), substantial outcome heterogeneity, unsurmountable difficulties in quality control, immunogenicity, and ethical restrictions. Therefore, researchers gradually switched to transplantation of homogenous cells (defined as cell populations containing only one cell type that was extracted, isolated, expanded, and characterized). These comprise neural progenitor cells, fetal stem cells, bone marrow mesenchymal stem cells, retinal pigment epithelial cells, or induced pluripotent stem cells. With the advances in regenerative medicine, engineered cells are being tested as well. Lately, implantation of autologous, induced pluripotent stem cell-derived midbrain dopaminergic progenitor cells was reported [ 4 ], which may help to overcome ethical concerns if used properly. Although homogeneous cell transplantation is translationally promising, mixed results were reported from individual trials and no meta-analysis of those results has been conducted so far. A meta-analysis is therefore necessary to provide an overall assessment of the safety and efficacy of cell-therapy approaches in PD. In this study, we systematically reviewed all clinical trials on tissue or cell transplantation for PD and performed a meta-analysis for homogenous cells in treatment of PD.

This systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines [ 5 ].

Search strategy

We systematically identified all clinical trials investigating cell-therapies for PD indexed in PubMed, Embase, Web of Science, and Cochrane databases before July 2023. The search terms were: (Parkinson disease OR Parkinson’s disease OR Parkinsonian disorders OR Parkinsonism OR Parkinsonisms OR Parkinson OR Parkinsons) AND (cell therapy OR cell therapeutics OR cell treatment OR cell treatments OR transplantation OR implantation), filtering for clinical trials. Only reports in English language were included.

FW and ZWS (review authors) screened studies for initial inclusion based on titles and abstracts. Full text screening for eligibility was performed if an initial decision could not be made. In case FW and ZWS could not reach a consensus, SL was consulted, followed by discussion and joint consensus in all cases. We also screened related reviews, together with reference lists of included publications, to identify other relevant articles [ 2 , 6 , 7 , 8 , 9 ].

Inclusion and exclusion criteria for the systematic review

The inclusion criteria were: (1) recruited patients were diagnosed with idiopathic PD; (2) cell or tissue transplantation; (3) randomized controlled trials (RCTs), open-label studies, cohort studies, case reports, prospective studies, or retrospective studies.

Exclusion criteria were: (1) trials focusing on secondary PD or Parkinsonism-plus syndrome; (2) transplantation of more than one tissue type; (3) reviews and book chapters.

Additional inclusion and exclusion criteria for the meta-analysis

The studies included in the systematic review were further screened for the meta-analysis with the following inclusion criteria: (1) transplantation with homogenous cell populations (containing only one type of cells); (2) using objective methods to evaluate treatment responses such as imaging, biochemical indicators or quantitative scales, including Unified Parkinson Disease Rating Scale (UPDRS), or its part II/III (UPDRSII/UPDRSIII), Hoehn and Yahr (H&Y) Staging Scale, Beck Depression Inventory (BDI), Beck Anxiety Inventory, Mini-mental State Examination (MMSE), Parkinson's Disease Quality of Life Questionnaire, or Schwab and England Scale; (3) quantitative data available before and after cell-therapy.

Exclusion criteria were: (1) missing or incomplete reporting of efficacy endpoints or sample size; (2) transplantation of mixed or uncharacterized cell populations; (3) case reports. The study selection process is presented in Fig.  1 a.

figure 1

a PRISMA flow diagram. b Pie chart of the total number of publications on different types of tissue or cell transplantation between 1982 and 2021. c Numbers of publications on different types of tissue or cell transplantation in each decade. The numbers of articles on embryonic mesencephalic tissue transplantation published in 1982–1991, 1992–2001, 2002–2011, 2012–2021 are 8, 39, 16 and 3, respectively. Articles reporting adrenal medulla transplantation are 12, 4, 0, and 0. Articles reporting sympathetic ganglion transplantation are 0, 3, 1 and 0. Articles on transplantation of other tissue are 0, 0, 2 and 1. Transplantation of homogenous cell populations are 0, 0, 6 and 11, respectively

Data extraction

Data regarding study population, intervention, and outcome were extracted into a standardized form from texts and graphs in each study by the review authors. When only graphic representation was available, values of mean and standard deviation (SD) or standard error (SE) were estimated from high-resolution digital graphs using GetData Graph Digitizer v2.20. Study information including cell source, grafting location, cell dose, sample size, patient age, disease duration, follow-up duration, primary and secondary endpoints, baseline (before transplantation) data, the clinical outcome information, as well as adverse events were collected. Adverse events were defined as an anticipated or unanticipated untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) whether or not related to cell transplantation. Neurological function before and after cell transplantation was compared for individual patients to evaluate treatment effects (self-comparison). For RCTs, baseline and outcome data were collected from the treatment groups. SE was converted to SD only when SE was reported.

Outcomes of interest were quantitative neurological scale scores in the ‘on’ or ‘off’ state. The ‘off’ state was defined as a period in which the patients withdrew antiparkinsonian medication for 12 h [ 10 ]. The ‘on’ state was at the time of the patients’ peak response to antiparkinsonian medication [ 10 ].

Risk of bias assessment

FW and ZWS independently assessed the risk of bias at the study level of included RCTs and non-RCTs in accordance with the Cochrane Collaboration Guidelines [ 11 ]. The risk of bias was assessed as ‘low’, ‘moderate’, ‘high’ or ‘incomplete reporting’ across the following domains: randomization; allocation concealment; blinding of therapists (intervention supervisors); blinding of patients; blinding of outcome assessors; handling of incomplete data (use of intention-to-treat analysis); selective reporting; and multivariate adjustment for potential confounders. Discrepancies in the risk of bias assessment were resolved by discussion among review authors and SL.

Statistical analysis

The mean difference (MD) or standardized mean difference (SMD) in quantitative neurological scale scores before and after cell-therapy was analyzed to evaluate the treatment effects. Forest plots were created to depict both the pooled MD or SMD along with their 95% confidence intervals (CI). The statistical significance of the pooled effect size of all studies was judged by a Z-test. A P value < 0.05 was considered statistically significant. We considered only trials that demonstrated clinical homogeneity to be appropriate for meta-analysis. Potential heterogeneity between studies was initially explored through a visual exploration of the forest plots. A test for statistical heterogeneity (a consequence of clinical or methodological diversity, or both, among trials) was then performed using Cochran’s Q-statistic test ( P value < 0.1 indicating significance) and I 2 analysis using the following equation:

in which Q is the Chi 2 statistic and df is its degrees of freedom. This describes the percentage of variability in effect estimates that is due to heterogeneity rather than sampling error (chance). Values greater than 50% are considered to represent substantial heterogeneity. When values were > 70%, we attempted to interpret the variation. If the value was less than 30%, we presented the overall estimate using a fixed-effect model. If there was evidence of heterogeneity ( I 2  > 30%) between trials, we used a random-effect model based on the DerSimonian and Laird method [ 12 ]. A leave-one-out sensitivity analysis was performed by iteratively removing one study at a time to confirm whether the findings were driven by any single study. Potential publication bias was evaluated using funnel plots. Review Manager 5.3 was used to complete all statistical calculations.

Study characteristics and systematic review of the literature

Overview on retrieved records.

The initial search returned 903 records, of which 136 were retrieved for full-text review (Fig.  1 a). One hundred and six articles were included in the systematic review [ 4 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 ]. Eighty-nine articles reported tissue transplantation or transplantation of mixed cell populations, including 66 articles using embryonic mesencephalic tissues (Additional file 9 : Table S1) [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 ], 16 articles reporting adrenal medulla tissue transplantation (Additional file 10 : Table S2) [ 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 ], two articles reporting carotid body tissue transplantation [ 95 , 96 ], four sympathetic ganglion tissue transplantation articles [ 97 , 98 , 99 , 100 ], and one adipose-derived stromal vascular fraction cell transplantation (Fig.  1 b) [ 101 ]. Seventeen publications reported transplantation of homogenous cell populations [ 4 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 ]. One hundred and four articles explored treatment efficacy, 63 articles reported safety, 92 articles investigated motor symptoms, and 18 articles examined non-motor symptoms. There were 84 articles using allotransplantation, 5 articles on xenotransplantation, and 17 articles on autotransplantation.

Changes in predominantly used cell material over time

Predominantly used cell sources for PD treatment changed over time (Fig.  1 c). Adrenal medulla tissue transplantation was the most widely studied approach before 1991 (n = 12) and was observed until 2001, but not thereafter. Embryonic mesencephalic tissue transplantation was investigated across all four decades and with most reports published in 1992–2001 (n = 39), gradually decreasing after 2002. Autonomic ganglion tissue transplantation was performed in a few studies between 1992–2011 (n = 3 + 1). Other tissues were investigated by one or two studies only. Treatment with homogenous cell populations became a research focus after 2002 and the most frequently used treatment strategy in the recent decade.

Transplantation of allogenic tissues

A total of 297 patients receiving embryonic mesencephalic tissue transplantation were included in this review. These studies investigated different outcomes using a broad range of methods including structural imaging, functional imaging, electrophysiology, biochemical indicators, functional outcome measurements by various scales, and pathological studies by autopsy. Some studies indicated that transplants partially replaced dopaminergic neurons following intra-striatal transplantation, and improved symptoms [ 41 , 46 , 51 , 75 ]. Double-blind, sham-controlled clinical trials did not confirm statistically significant benefits from fetal mesencephalic tissue transplantation but revealed adverse events such as GID [ 20 , 23 ].

Transplantation of autologous tissues

The usage of autologous cells is not limited by ethical considerations and avoids severe immune reactions. Autologous cell or tissue transplantation to supply DA was therefore investigated as a potential treatment for PD patients. These autologous DA-secreting cells or tissues included adrenal medulla and carotid body tissues, and sympathetic neurons. In the pioneering work performed by Backlund and collaborators [ 94 ], autologous adrenal medulla cells were implanted into the striatum of four patients to provide a local catecholamine source, but the beneficial effects were minimal. In the following 10 years, clinical studies on adrenal medulla transplantation of 148 PD patients yielded similar results and several autopsies demonstrated that the transplanted adrenal cells did not survive in the host brain [ 118 ].

The carotid body contains neural crest-derived dopaminergic glomus cells that are similar to the chromaffin cells of the adrenal medulla. These cells function as arterial oxygen sensors and release large amounts of dopamine in response to hypoxia. In addition, glial cell line–derived neurotrophic factor (GDNF) secreted from the carotid body might exert neuroprotective effects for these dopaminergic glomus cells as well as nigrostriatal neurons [ 119 ]. A pilot study and a phase I-II blinded clinical study were performed using bilateral intrastriatal transplantation of autologous carotid body cells in patients with advanced-stage PD (n = 6 and 13, respectively) [ 95 , 96 ]. Functional improvement was seen in five and ten patients, respectively, and no patients developed GID.

Some studies investigated the potential of autologous sympathetic neurons since the ganglion contains not only norepinephrinergic but also dopaminergic cells. Long-term clinical evaluation revealed that unilateral intrastriatal implantation of autologous cervical sympathetic ganglion tissue results in a significant improvement of PD symptoms, particularly akinesia and gait disturbance, and a reduction in the patient’s daily levodopa intake [ 99 ]. Following the development of video-guided endoscopic thoracic surgery, it became possible to safely excise three or more ganglia from the thoracic sympathetic trunk in a minimally invasive manner. This option may augment the amount of available tissue, thereby increasing the number of implantation sites. One study endoscopically excised and re-transplanted thoracic sympathetic ganglia in a total of five PD patients [ 98 ]. These autografts were found to improve the patients’ performance by reducing the time spent in the off phase. However, there have been no further clinical studies using these cells.

One study investigated intranasal administration of autologous adipose-derived stromal vascular fraction cells in two patients [ 101 ]. Both patients exhibited improvements in motor and non-motor functions one and five years after transplantation. There is, however, no clear understanding of the underlying mechanism, and any reported results should be confirmed in future studies.

Meta-analysis on studies investigating transplantation of homogenous cell populations

Seventeen publications reported transplantation of homogenous cell populations and 11 were eligible for this meta-analysis [ 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 ]. Two publications were reporting results from one study [ 112 , 113 ]. Two publications were case reports [ 4 , 117 ]. Three publications did not report the quantitative data necessary for this analysis. Attempts to contact the corresponding authors failed and these studies were therefore excluded [ 114 , 115 , 116 ]. An overview of research protocols and subject characteristics is shown in Table 1 .

Risk of bias analysis

The risk of bias assessment is summarized in Table 2 . Ten studies were non-RCTs that did not describe the processes of random sequence generation or allocation concealment in sufficient detail. They were considered as incomplete regarding the risk of bias reporting when evaluating selection bias. In most of the studies included for meta-analysis, it was neither practical nor possible to blind the participants or therapists. This was considered a low risk of performance bias for the therapists, but a moderate risk for the participants. Those studies reporting a dropout or loss of follow-up rate higher than 20% were believed to have a high level of attrition bias. Studies were rated as high-risk for detection bias when neither employing intention-to-treat principles in the data analysis nor describing dropouts, nor blinding evaluators to treatment. All other bias assessment domains shown in Table 2 were considered to have a low risk of bias.

Effects of homogeneous cell populations in PD

Disease course and disability.

UPDRS (monitoring the disease course and the degree of disability) or UPDRSIII (evaluation of motor function) scores were examined in ‘on’ or ‘off’ state at various post-intervention time points. These follow-ups were different across the nine studies reporting those and varied from 1 to 57 months (last follow-up, Table 1 ). A total of 210 patients were investigated in the included trials. Meta-analysis was performed on the last follow-up across studies, and at intermediate follow-up time points (3-, 6-, 12-, 24-, and ≥ 36-month follow-ups) when those were reported by the respective studies.

The meta-analysis revealed overall better post- versus pre-treatment function although considerable heterogeneity was evident (Additional file 1 : Fig. S1). There was a beneficial effect of homogenous cell-therapy on UPDRS scores in the ‘off’ state at the last follow-up and at 3-, 6-, 12- and 24-month follow-ups, but not at the ≥ 36-month follow-up (Fig.  2 ). However, the latter was only reported by two studies (Fig.  2 ). UPDRS scores showed relative homogeneity in the ‘off’ state at 3-, 6-month and ≥ 36-month follow-up analysis (Fig.  2 ). Moreover, cell treatment improved UPDRS scores in the ‘on’ state at the 12-month follow-up, but not at the last follow-up, or at 24-, ≥ 36-month follow-ups (Additional file 2 : Fig. S2). There was no profound heterogeneity among 12-, 24-, ≥ 36-month follow-ups, but at the last follow-up. This might be explained by different transplantation paradigms. For instance, Brazzini et al. infused bone marrow stem cells intraarterially [ 106 ], while other studies administered cells directly into the basal ganglia. Removing the study of Brazzini et al. (leaving-one-out analysis) reduced the heterogeneity to 16%, but the overall result remained unchanged (95% CI − 8.95 to 19.03). When analyzing the H&Y scale, we revealed the overall positive effects of cell-therapy at the last assessed timepoints in ‘on’ or ‘off’ state (Additional file 3 : Fig. S3). However, there was no change in the levodopa equivalent dose of antiparkinsonian medications after 12 months ( P  = 0.56, I 2  = 0%, 95% CI − 103.43 to 191.50).

figure 2

UPDRS scores pre- versus post-transplantation in the ‘off’ state at last follow-up, or 3-, 6-, 12-, 24-, and ≥ 36-month follow-ups. The number of studies included in each analysis are 6, 3, 3, 5, 3, and 2, respectively. If the I 2 value is less than 30%, a fixed-effect model is used. If the I 2 value is greater than 30%, a random-effect model is used. The sizes of the squares represent the weight that each study contributes. The diamond at the bottom represents the overall effect. CI, confidence interval (represented by the lines)

Motor symptoms

Seven studies measured the effects of homogenous cell-therapy on motor symptoms [ 102 , 104 , 107 , 108 , 110 , 111 , 112 ]. A random-effect model was used to compare the pre- versus post-treatment UPDRSIII scores in the ‘off’ state at the study last follow-up. The meta-analysis yielded a better outcome after cell treatment, but the heterogeneity was high (Fig.  3 ). This might be related to the design of the study by Lige et al. who did not use a fixed observation time. Analyzing the UPDRSIII scores after cell treatment in the ‘off’ state at 3-, 6-, 12-, 24-, and ≥ 36-month follow-ups revealed positive effects (Fig.  3 , Additional file 4 : Fig. S4). Analyzing UPDRSIII scores in the ‘on’ state revealed beneficial effects of cell treatment at the 6- and 24-month follow-ups compared to baseline status, but neither at the last follow-up nor at 3- or 12-month follow-ups (Fig.  4 ). The inter-study heterogeneity was low at the last follow-up and at 3-, 6-, and 24-month follow-ups (Fig.  4 ). The 12-month follow-ups showed a high heterogeneity. This can be explained by the study of Gross et al. [ 111 ], as its RCT design was different from the other three open-labeled pilot studies. Leaving this study out reduced the I 2 value to 0%.

figure 3

UPDRSIII score pre- versus post-transplantation in the ‘off’ state at last follow-up, or 3-, 6-, 12-, 24-, and ≥ 36-month follow-ups. The number of studies included in each analysis are 7, 4, 3, 5, 4, and 3, respectively. If the I 2 value is less than 30%, a fixed-effect model is used. If the I 2 value is greater than 30%, a random-effect model is used. The sizes of squares represent the weight that each study contributes. The diamond at the bottom represents the overall effect. CI, confidence interval (represented by the lines)

figure 4

UPDRSIII score pre- versus post-transplantation in the ‘on’ state at last follow-up, or 3-, 6-, 12-, 24-, and ≥ 36-month follow-ups. The number of studies included in each analysis are 4, 3, 2, 4, and 3, respectively. If the I 2 value is less than 30%, a fixed-effect model is used. If the I 2 value is greater than 30%, a random-effect model is used. The sizes of squares represent the weight that each study contributes. The diamond at the bottom represents the overall effect. CI, confidence interval (represented by the lines)

Non-motor symptom-depression

Three studies examined the effects of homogenous cell-therapy on non-motor symptoms [ 106 , 107 , 109 ]. The Beck Depression Inventory (BDI) was used to evaluate the degree of depression in patients but did not reveal significant differences after cell treatment. There was considerable heterogeneity between studies probably resulting from diverse transplantation modes (using bilateral basal ganglia transplantation [ 107 ], combined intravenous and subcutaneous routes [ 109 ], and intra-arterial transplantation [ 106 ], respectively) (Additional file 5 : Fig. S5).

Activities of daily living (ADL)

ADL were assessed using UPDRSII or the Schwab and England score. Four studies examined the UPDRSII scores in the ‘off’ state at the last follow-up [ 107 , 108 , 110 , 112 ]. A fixed-effect model revealed a better outcome after homogenous cell-therapy. Three studies assessed UPDRSII scores in the ‘on’ state (all used allogeneic cells) but did not report treatment effects. There was no obvious heterogeneity (Fig.  5 ) [ 107 , 110 , 112 ].

figure 5

UPDRSII score pre- versus post-transplantation in the ‘off’ and ‘on’ states at the last follow-up. The number of studies included are 4 and 3, respectively. Fixed-effect models are used. The sizes of squares represent the weight that each study contributes. The diamond at the bottom represents the overall effect. CI, confidence interval (represented by the lines)

Patients potentially benefited from cell-therapy

There was no study investigating whether the effects of cell-therapy are influenced by patient sex. All studies included had equivalent male/female ratio and an average disease course of more than 5 years. The average age was between 47.2 and 66.4 years. Six studies included in the meta-analysis clearly stated that the enrolled patients had positive responses to dopaminergic therapy [ 102 , 104 , 107 , 110 , 111 , 112 ]. Five studies did not specify levodopa responsiveness. In the analyses of UPDRS scores in the ‘off’ state, the proportion of levodopa-responsive patients was 100%, 100%, 86.5%, 100% and 100% at 3-, 6-, 12-, 24-, and ≥ 36-month follow-ups and 61.6% at last follow up, respectively (Fig.  2 ). The fraction of levodopa-responsive patients was 76%, 100%, 100%, 100%, 100% at 3-, 6-, 12-, 24-, and ≥ 36-month follow-ups, and 81.4% at last follow-up, in the analyses of UPDRSIII scores in the ‘off’ state, respectively (Fig.  3 ). The patients who were responsive to dopaminergic therapy showed functional improvements on UPDRS, UPDRSIII, and UPDRSII scores in the ‘off’ state at the last follow-up, but not in the ‘on’ state (Fig.  6 ).

figure 6

UPDRS, UPDRSIII and UPDRSII scores pre- versus post-transplantation in the ‘off’ and ‘on’ states at the last follow-up with levodopa responders. The number of studies included are 4, 6, 3, 2, 5, and 3, respectively. If the I 2 value is less than 30%, a fixed-effect model is used. If the I 2 value is greater than 30%, a random-effect model is used. The sizes of squares represent the weight that each study contributes. The diamond at the bottom represents the overall effect. CI, confidence interval (represented by the lines)

Impact of cell immunogenicity and cell type on outcome

Eight studies used allogeneic, and three studies used autologous cells for transplantation. Allogeneic cells (neural progenitor cells, fetal stem cells, retinal pigment epithelial cells, and bone marrow mesenchymal stem cells) showed beneficial effects on UPDRS, UPDRSIII, and UPDRSII scores in the ‘off’ state at the last follow-up, but not in the ‘on’ state (Additional file 6 : Fig. S6) [ 102 , 103 , 107 , 108 , 110 , 111 , 112 ]. There were considerable heterogeneities in the UPDRSIII score analyses in the ‘off’ state, which might be explained by one study not defining fixed observation time points (last follow-up ranged from 7–57 months)[ 108 ]. Removing this study reduced the I 2 value to 37% but did not change the overall result. When autografts (mesenchymal stem cells that cannot differentiate into neural cells) were used, no beneficial effect was observed on H&Y scores in ‘off’ or ‘on’ state (Additional file 7 : Fig. S7) [ 105 , 106 ]. Even though homogenous cell-therapy in general and allogeneic cells in particular showed positive effects on motor function in the ‘off’ state, autologous cell transplantation did not show such effects.

Several types of cells were transplanted including neural progenitor cells (n = 2), fetal stem cells (n = 1), bone marrow mesenchymal stem cells (n = 4), other bone marrow stem cells (including exact cell type not specified, n = 1), and retinal pigment epithelial cells (n = 3). UPDRS or UPDRSIII assessments in the ‘off’ states at the last follow-up revealed better outcomes after retinal pigment epithelium cell and stem/progenitor cell treatment (Fig.  7 ). The heterogeneity was low in retinal pigment epithelial cell studies. However, the UPDRSIII analysis of stem/progenitor cell-therapy revealed high heterogeneity, potentially due to the study of Lige et al. not defining fixed observation time points [ 108 ]. Removing this study reduced the I 2 value to 21%.

figure 7

UPDRS and UPDRSIII scores pre- versus post-transplantation in the ‘off’ state at the last follow-ups after retinal pigment epithelium cell and stem/progenitor cell treatment. The number of studies included are 2, 3, 4, and 4, respectively. Random-effect models are used. The sizes of squares represent the weight that each study contributes. The diamond at the bottom represents the overall effect. CI, confidence interval (represented by the lines)

Transplantation route

Among the 11 studies included in this meta-analysis, six studies performed intraparenchymal transplantation into the basal ganglia (Table 1 ) [ 103 , 107 , 108 , 110 , 111 , 112 ]. Unilateral and bilateral intraparenchymal transplantation was performed in three studies each. One study investigated intravenous infusion of allogeneic bone marrow-derived mesenchymal stem cells [ 102 ]. One study transplanted autologous mesenchymal stem cells through intravenous or tandem (intranasal + intravenous) injections [ 104 ]. One study combined intravenous and subcutaneous transplantation of fetal stem cells [ 109 ]. One study injected autologous bone marrow mesenchymal stem cells via intrathecal and intravenous injection [ 105 ]. One study infused bone marrow stem cells using a superselective intraarterial approach to the posterior region of the circle of Willis [ 106 ]. Basal ganglia transplantation resulted in beneficial effects on both UPDRS and UPDRSIII scores in ‘off’ state at the last follow-ups. Non-basal ganglia transplantation improved UPDRSIII scores. However, the I 2 value for UPDRSIII scores were high for transplantation into basal ganglia, which might again be explained by the study of Lige et al. (Fig.  8 ) [ 108 ].

figure 8

UPDRS and UPDRSIII scores pre- versus post-transplantation in the ‘off’ state at the last follow-ups after basal ganglia and non-basal ganglia transplantation. The number of studies included are 5, 5, and 2, respectively. If the I 2 value is less than 30%, a fixed-effect model is used. If the I 2 value is greater than 30%, a random-effect model is used. The sizes of squares represent the weight that each study contributes. The diamond at the bottom represents the overall effect. CI, confidence interval (represented by the lines)

The cell doses used for transplantation were between 1 and 10 × 10 6 /kg in the ten studies investigated. In one study, four doses (1, 3, 6, or 10 × 10 6 /kg) of allogeneic bone marrow-derived mesenchymal stem cells were administered intravenously to investigate a potential dose-dependent efficacy [ 102 ]. The results showed that all doses showed effects on motor symptoms in the ‘off’ state. However, the highest dose achieved the maximum absolute improvement at the 52 weeks follow-up and reduced the UPDRS motor and total scores in the ‘off’ state. Therefore, the included studies suggested that cell doses between one to ten million were all effective.

Imaging readouts

Seven included studies applied magnetic resonance (MR) imaging for outcome evaluation [ 102 , 103 , 106 , 107 , 108 , 110 , 111 ], among which four [ 107 , 108 , 110 , 111 ] investigated safety endpoints including inflammatory responses, tumor formation, bleeding, and edema after cell transplantation. Three other studies [ 102 , 103 , 106 ] used MR spectroscopy, MR perfusion, and MR tractography for efficacy evaluation. In one study, MR spectroscopy revealed a significant increase of the mean n - acetylaspartate/creatine ratio in basal ganglia after transplantation [ 106 ]. One study showed MR perfusion increased overall from baseline to 24 weeks post infusion in all basal ganglia structures [ 102 ]. Another study reported a statistically non-significant trend of improvement in fractional anisotropic (FA) values of MR tractography in the genu and the cerebral peduncles steadily over a period of 12 months after transplantation [ 103 ]. Two studies employed positron emission tomography (PET) imaging to evaluate the efficacy [ 107 , 110 ]. The radiopharmaceuticals included FDOPA, DTBZ, and 11 C-β-CFT. FDOPA and DTBZ imaging showed a statistically non-significant trend toward enhanced midbrain dopaminergic activity at one year after grafting in one study [ 107 ]. The other study showed a statistically non-significant trend towards increased dopamine release in 11 C-β-CFT PET imaging during the first 6 months after transplantation [ 110 ]. These studies suggested that cell-therapy partially replaced dopaminergic neurons. Due to the heterogeneity in imaging methodology, the limited number of studies and overall small sample sizes, however, prevented a meaningful meta-analysis of the imaging readouts regarding efficacy.

Adverse events of homogenous cell transplantation

The reports for adverse events of homogenous cell-therapy for PD are listed in Table 3 . No tumor formation or severe immune rejections were observed. Two trials reported GID [ 102 , 111 ]. There were other adverse events including surgical injury and complications, such as phlebitis and hematoma. Psychonosema was noted such as hallucination or disturbance in attention.

Sensitivity analysis

Sensitivity analyses were performed to evaluate the robustness of the estimated pooled effect size for UPDRS, UPDRSIII, UPDRSII scores and non-motor symptoms. The pooled effect was stable for UPDRSIII and UPDRSII in the ‘off’ state and non-motor symptoms, indicating that these results were not driven by any single study. However, when either the study by Brazzini et al. [ 106 ] or the one by Lige et al. [ 108 ] was removed, statistical significance was lost for the pooled effect size of homogenous cell-therapy on H&Y scores in the ‘on’ or ‘off’ state at the last follow-up. On the contrary, when the study of Madrazo et al. [ 107 ] was removed, cell-therapy became beneficial for UPDRS and UPDRSIII scores in the ‘on’ state at the last follow-up. Removing the study of Gross et al. [ 111 ] also resulted in the detection of a cell treatment effect on UPDRSIII scores in the ‘on’ state at the 12-month follow-up.

Publication bias

Funnel plots were plotted for the meta-analysis including more than 5 studies (Additional file 8 : Fig. S8). These plots were symmetrical and evenly distributed, and few effects fell outside the 99% CI, suggesting that the present meta-analyses were not substantially affected by publication bias.

Tissue transplantation

Intracerebral grafting of fetal mesencephalic tissue, which is rich in dopaminergic neuroblasts, was first reported in 1979, ameliorating the symptoms of experimental PD rats [ 120 , 121 ]. Thereafter, about 400 PD patients were grafted with human fetal mesencephalic tissue in the 1980s–1990s. Fetal tissue grafts have survived over two decades in some patients despite ongoing PD pathology [ 122 ]. In addition, several trials showed engraftment of fetal tissue with wide outgrowth and robust innervation of the host striatum by donor-derived DA neurons [ 54 , 56 , 58 , 66 , 123 , 124 ]. However, due to GID, fetal tissue transplantation was abandoned. The overall discouraging results may be partly related to differences between studies in cell sources, preparation, and transplantation paradigms [ 23 , 124 ]. In addition, multiple fetal donors (typically 3–5) were pooled to obtain sufficient numbers of cells for one patient. This may contribute to the heterogeneity of outcomes and may indicate a lack of material for widespread clinical usage. Ethical arguments also limit fetal tissue transplantation. Therefore, transplantation of human fetal mesencephalic tissue is very unlikely to be developed into a routine treatment for PD patients.

Autologous adrenal medulla and carotid body tissues, and sympathetic neurons were explored as PD treatments because these can either secret DA or exert neurotrophic effects, but their precise therapeutic mechanism is uncertain [ 95 , 96 , 97 , 98 , 99 , 100 ]. Tissue transplantation was less investigated in the recent decade. Lately, the concept experienced a renaissance due to advances in regenerative medicine and tissue engineering, using optimized grafting and defined immunosuppression protocols [ 2 ]. Successful in-vitro differentiation of embryonic stem cells [ 125 , 126 , 127 ] or induced pluripotent stem cells [ 4 ] towards a midbrain dopaminergic fate may allow the development of cell-therapies for PD while avoiding many practical and ethical concerns regarding tissue transplantation, although there are still many challenges in translating in-vitro success to in-vivo applications, and potential ethical concerns surrounding embryonic stem cells usage. What remains is the need for cell transplants that can not only functionally integrate but survive in the host brain over long periods.

Therapeutic effects of homogenous cell-therapy on PD

To the best of our knowledge, this is the most comprehensive meta-analysis of clinical trials on cell treatments for PD to date. Both cell origin and the site of cell transplantation varied considerably across the studies. Most transplantations (6 out of 11) were performed into basal ganglia uni- or bilaterally. Follow-up time ranged from 1 to 57 months. The key finding from our meta-analysis is that homogenous cell transplantation significantly improves clinical outcomes in PD patients regarding overall disease severity, motor symptoms, and ADL in the ‘off’ state.

The main outcome measurement in our meta-analysis was based on the UPDRS score which is believed to be less susceptible to observer bias than other scores [ 128 ]. Therefore, it is less likely that the clinical improvements observed can be solely attributed to observer bias. Our findings suggest that the investigated cell treatments have a robust effect on the ‘off’ state at the 3-, 6-, 12-, 24-, and even ≥ 36-month follow-ups for motor symptoms. There was indication that the magnitude and duration of functional improvement induced by dopaminergic grafts depend on patient selection, with good preoperative response to L-dopa predicting good response to the graft [ 129 , 130 ]. In this meta-analysis most of the patients included were responsive to dopaminergic therapy, and those patients may also be responsive to cell-therapy. Patients with DA neuron loss restricted to the caudate and putamen are more likely to experience long-term benefits from dopaminergic grafts placed in these areas [ 14 , 25 , 129 , 130 ]. In contrast, long-lasting beneficial outcomes in PD patients with more widespread DA neuron loss are less likely [ 14 ].

Most of the trials in our meta-analysis included PD patients with a good response to L-dopa. This may explain why UPDRS and UPDRSIII at the ‘on’ state did not improve much, as the combination of both treatments would require a significant additional effect that may not be detected with the overall limited numbers of patients investigated. No difference between neurological function pre- and post-transplantation was found in the UPDRS score in the ‘off’ state at ≥ 36 months. Graft function may be compromised by delayed immune reactions, previously characterized by microglial infiltration into the graft [ 23 ]. However, UPDRSIII scores in the ‘off’ state at ≥ 36 months provide preliminary evidence that the cell graft was still functional, but more rigorous RCTs and long-term follow-up studies, especially those ≥ 36 months are needed to confirm this. Those should include tailored assessment of graft functionality, for instance by sophisticated brain imaging.

Only few clinical trials investigating homogenous cell-therapy for PD have focused on the management of non-motor symptoms: four articles investigated cognition [ 102 , 103 , 107 , 109 ], four articles reported depression [ 104 , 106 , 107 , 109 ], one studied anxiety article [ 107 ], and two examined sleep-disorder [ 104 , 109 ]. Although a significant decrease of non-motor symptoms and depression, as well as an improvement in objective parameters of sleep quality, were reported in PD patients after cell treatment in single studies [ 109 ], we could not confirm these findings in our meta-analysis. Several factors could have contributed to this. Firstly, non-motor symptoms may originate from degeneration outside the striatum or in non-dopaminergic systems that may be difficult to target with cell-therapy. Secondly, the cell grafts investigated may simply lack the ability to counter these symptoms. Third and most importantly, the relatively high inter-study heterogeneity regarding cell type and source, transplantation site, and other aspects may just have ‘masked’ minor yet clinically meaningful effects on these endpoints. Therefore, it is crucial to scrutinize non-motor symptoms in future investigations. In summary, the overall positive impact on ADL parameters observed in our meta-analysis may primarily originate from motor symptom improvements. However, overall results should be interpreted with caution as the overall number of available and included studies is relatively low.

Effects of different cell sources and transplantation modes on efficacy

Most of the included studies (n = 8) transplanted allogeneic cells for PD patients and exhibited robust beneficial effects on UPDRS, UPDRSIII, and UPDRSII scores in the ‘off’ state. However, autografts were ineffective in symptoms examined by H&Y score changes in ‘off’ or ‘on’ states as there were not sufficient autograft transplantation studies to be combined to evaluate the UPDRS changes. The three articles evaluating autografts all used bone marrow mesenchymal stem cells [ 104 , 105 , 106 ], which may not differentiate into neural tissue. However, they may exert beneficial immunomodulative and neuroprotective effects. Moreover, six out of the eight articles evaluating allogeneic cells used neural progenitor cells, fetal stem cells, or retinal pigment epithelial cells. Those might be able to differentiate into neuronal cells. Thus, allogeneic cells and autologous cells likely have different mechanisms of action. Therefore, it is rational to speculate that the overall positive effects of homogenous cell-therapy for PD patients in our meta-analysis were mainly due to allogeneic cell transplantation studies and that allogeneic cells may be a better option for PD treatment, particularly, retinal pigment epithelium cell and stem/progenitor cell. Besides, allogeneic cells have some logistical advantages as they can be obtained and prepared in advance and under standardized conditions. They might also be advantageous in inherited PD. However, when using allogeneic cells, the immunological barrier represents a formidable obstacle for the transplanted cells to survive and execute therapeutic effects relying on differentiation and functional integration. Fortunately, with the development of modern immunosuppressants, graft survival and side effects have been greatly improved [ 131 ].

Unexpectedly, we observed that transplantation outside basal ganglia was also effective to improve motor function in PD patients. In these two studies, the intravenously infused bone marrow mesenchymal stem cells were likely to improve PD symptoms through immunomodulatory mechanisms, such as decreasing inflammatory cytokine production, reducing microglial activation and a-synuclein oligomerization [ 102 , 104 ]. This observation may be clinically relevant because such transplantation, in particular systemic cell delivery, may not only be safer and easier to perform, but also less expensive and time-consuming. However, this result is based on a limited number of studies and thus will require confirmation, and the likelihood of immunological consequences is far greater after systematic cell delivery.

Other factors as, for instance, gender, age, and disease courses of the patients may also act as confounding factors. However, due to the lack of available raw data, we were unable to analyze their impact on reported functional outcomes after cell-therapy.

Adverse events of homogenous cell-therapy

No tumor formation or severe immune rejections were reported in the included studies, but one trial reported a case of GID, and another trial reported four cases of possibly GID. Off-state GID was a relatively frequent adverse event after human fetal mesencephalic tissue transplantation. The interpretation of this phenomenon is difficult. Modeling studies suggest that some form of L-DOPA-induced postsynaptic supersensitivity, established before transplantation, may play a role [ 132 , 133 ]. Moreover, small, intracerebral transplants may be more prone to cause GID by forming ‘hot-spots’ of DA release, while the surrounding striatum remains supersensitive [ 133 , 134 ]. Finally, a potential role of excessive serotonin innervation has been discussed [ 8 , 135 , 136 ]. Fetal mesencephalic tissue often used for transplantation also contains serotonergic neurons, and studies on 6-hydroxydopamine-induced PD models suggested that these could exacerbate dyskinesia induced by L-DOPA [ 135 ]. Clinical research suggested that a non-optimal ratio between serotonergic and dopaminergic neurons (or their progenitors) in grafts causes GID [ 136 , 137 , 138 ]. The relatively low incidence of GID in the studies included in our meta-analysis may be related to patient selection, improvement of surgical methods, and higher homogeneity of transplanted cells. Other adverse events such as surgical complications (phlebitis and hematoma) and psychonosema were generally rare. However, two included studies did not provide comprehensive adverse effect reports, which limit the understanding of potential risks associated with the intervention. Due to the inconsistency in reporting of adverse events, we were also unable to compare the safety profiles of different interventions. A thorough and robust safety analysis is imperative for future clinical trials.

Quality of evidence and limitations

Despite the generally encouraging results of our meta-analysis, it is important to keep in mind that most of the included studies were open-label, single-center trials, with outcome data not reported or inadequately described in some studies. Moreover, insufficient information on disease duration in some studies limits the understanding of how the disease stage could affect the treatment outcomes and impact the quality and reliability of the analysis. Although blinding of the participants and therapists was not possible, outcome assessors can be blinded. Nevertheless, a relatively large proportion of studies (n = 5, 41.7%) did not report blinding of outcome assessors. Thus, the results may still contain observer bias.

Another major limitation is that our meta-analysis cannot provide a thorough perspective on how cell-therapies for PD may be improved further. The main reasons are the small number of studies and the overall heterogeneity of cell and tissue types being used. While there is an overall positive effect of cell-based treatments, any kind of optimal approach cannot be identified from this relatively small dataset. Moreover, we can only speculate why systemic cell administration was effective or why overall best effects were obtained with allogeneic cells, and both findings may appear counter-intuitive. A combination of thorough preclinical and clinical research is required to solve these questions. Mechanistic investigations in relevant animal models should identify the most effective cell types and transplantation paradigms while multicenter, large-scale, and double-blinded RCTs are needed to verify the encouraging yet preliminary results of our meta-analysis. Alternative solutions, such as pharmacological therapy and deep brain stimulation, should also be considered in conjunction with cell-based therapies.

According to this meta-analysis, cell therapy was effective for improving disease severity and motor symptoms while also improving ADL in the ‘off’ state of PD patients, especially in levodopa responders. Allogenic cells exerted beneficial effects on these parameters, but autografts did not. Transplantation of cells to areas outside the basal ganglia, including system transplantation of cells, was able to induce therapeutic benefits. Some trials reported adverse events potentially related to the surgical procedure. One confirmed and four possible cases of GID were reported in two trials included in meta-analysis. Therefore, our results suggest modest yet clinically meaningful cell therapy effects in patients with PD although definitive evidence must be provided by future double-blinded large-scale RCTs. These should also monitor the long-term safety of cell-based interventions for PD while the optimal cell population and route of transplantation need to be defined. Cell-therapies in PD are not a stand-alone treatment but must always be considered in combination with established therapies.

Availability of data and materials

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

Activities of daily living

Beck Depression Inventory

Confidence interval

Fractional anisotropic

Glial cell line-derived neurotrophic factor

Graft-induced dyskinesia

Hoehn and Yahr Staging Scale

Mean difference

Mini-mental State Examination

Magnetic Resonance

Parkinson’s disease

Positron emission tomography

Randomized controlled trial

Standard deviation

Standard error

Standardized mean difference

Unified Parkinson Disease Rating Scale

Church FC. Treatment options for motor and non-motor symptoms of Parkinson’s disease. Biomolecules. 2021;11(4):612.

CAS   PubMed   PubMed Central   Google Scholar  

Harris JP, Burrell JC, Struzyna LA, Chen HI, Serruya MD, Wolf JA, et al. Emerging regenerative medicine and tissue engineering strategies for Parkinson’s disease. NPJ Parkinsons Dis. 2020;6:4.

Polgar S, Morris ME, Reilly S, Bilney B, Sanberg PR. Reconstructive neurosurgery for Parkinson’s disease: a systematic review and preliminary meta-analysis. Brain Res Bull. 2003;60(1–2):1–24.

CAS   PubMed   Google Scholar  

Schweitzer JS, Song B, Herrington TM, Park TY, Lee N, Ko S, et al. Personalized iPSC-derived dopamine progenitor cells for Parkinson’s disease. N Engl J Med. 2020;382(20):1926–32.

Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.

PubMed   PubMed Central   Google Scholar  

Sonntag KC, Song B, Lee N, Jung JH, Cha Y, Leblanc P, et al. Pluripotent stem cell-based therapy for Parkinson’s disease: current status and future prospects. Prog Neurobiol. 2018;168:1–20.

Lindvall O. Clinical translation of stem cell transplantation in Parkinson’s disease. J Intern Med. 2016;279(1):30–40.

Lindvall O, Björklund A. Cell therapeutics in Parkinson’s disease. Neurotherapeutics. 2011;8(4):539–48.

Yasuhara T, Kameda M, Sasaki T, Tajiri N, Date I. Cell therapy for Parkinson’s disease. Cell Transplant. 2017;26(9):1551–9.

Langston JW, Widner H, Goetz CG, Brooks D, Fahn S, Freeman T, et al. Core assessment program for intracerebral transplantations (CAPIT). Mov Disord. 1992;7(1):2–13.

Higgins J, Green S. The Cochrane Collaboration. Cochrane handbook for systematic reviews of interventions. New York: Wiley; 2011.

Google Scholar  

DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.

McRae C, Caspari J, Russell D, Ellgring H, Bezzant C, Greene P, et al. Video review of baseline performance on global ratings in a double-blind placebo surgery trial. Mov Disord Clin Pract. 2018;5(6):597–602.

Ma Y, Tang C, Chaly T, Greene P, Breeze R, Fahn S, et al. Dopamine cell implantation in Parkinson’s disease: long-term clinical and (18)F-FDOPA PET outcomes. J Nucl Med. 2010;51(1):7–15.

PubMed   Google Scholar  

McRae C, Cherin E, Yamazaki TG, Diem G, Vo AH, Russell D, et al. Effects of perceived treatment on quality of life and medical outcomes in a double-blind placebo surgery trial. Arch Gen Psychiatry. 2004;61(4):412–20.

Gordon PH, Yu Q, Qualls C, Winfield H, Dillon S, Greene PE, et al. Reaction time and movement time after embryonic cell implantation in Parkinson disease. Arch Neurol. 2004;61(6):858–61.

Trott CT, Fahn S, Greene P, Dillon S, Winfield H, Winfield L, et al. Cognition following bilateral implants of embryonic dopamine neurons in PD: a double blind study. Neurology. 2003;60(12):1938–43.

McRae C, Cherin E, Diem G, Vo AH, Ellgring JH, Russell D, et al. Does personality change as a result of fetal tissue transplantation in the brain? J Neurol. 2003;250(3):282–6.

Ma Y, Feigin A, Dhawan V, Fukuda M, Shi Q, Greene P, et al. Dyskinesia after fetal cell transplantation for parkinsonism: a PET study. Ann Neurol. 2002;52(5):628–34.

Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, et al. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med. 2001;344(10):710–9.

Nakamura T, Dhawan V, Chaly T, Fukuda M, Ma Y, Breeze R, et al. Blinded positron emission tomography study of dopamine cell implantation for Parkinson’s disease. Ann Neurol. 2001;50(2):181–7.

Olanow CW, Gracies JM, Goetz CG, Stoessl AJ, Freeman T, Kordower JH, et al. Clinical pattern and risk factors for dyskinesias following fetal nigral transplantation in Parkinson’s disease: a double blind video-based analysis. Mov Disord. 2009;24(3):336–43.

Olanow CW, Goetz CG, Kordower JH, Stoessl AJ, Sossi V, Brin MF, et al. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann Neurol. 2003;54(3):403–14.

Pogarell O, Koch W, Gildehaus FJ, Kupsch A, Lindvall O, Oertel WH, et al. Long-term assessment of striatal dopamine transporters in Parkinsonian patients with intrastriatal embryonic mesencephalic grafts. Eur J Nucl Med Mol Imaging. 2006;33(4):407–11.

Brundin P, Pogarell O, Hagell P, Piccini P, Widner H, Schrag A, et al. Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson’s disease. Brain. 2000;123(7):1380–90.

Hagell P, Crabb L, Pogarell O, Schrag A, Widner H, Brooks DJ, et al. Health-related quality of life following bilateral intrastriatal transplantation in Parkinson’s disease. Mov Disord. 2000;15(2):224–9.

Piccini P, Lindvall O, Björklund A, Brundin P, Hagell P, Ceravolo R, et al. Delayed recovery of movement-related cortical function in Parkinson’s disease after striatal dopaminergic grafts. Ann Neurol. 2000;48(5):689–95.

Hagell P, Schrag A, Piccini P, Jahanshahi M, Brown R, Rehncrona S, et al. Sequential bilateral transplantation in Parkinson’s disease: effects of the second graft. Brain. 1999;122(6):1121–32.

Wenning GK, Odin P, Morrish P, Rehncrona S, Widner H, Brundin P, et al. Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson’s disease. Ann Neurol. 1997;42(1):95–107.

Lindvall O, Sawle G, Widner H, Rothwell JC, Björklund A, Brooks D, et al. Evidence for long-term survival and function of dopaminergic grafts in progressive Parkinson’s disease. Ann Neurol. 1994;35(2):172–80.

Sawle GV, Bloomfield PM, Björklund A, Brooks DJ, Brundin P, Leenders KL, et al. Transplantation of fetal dopamine neurons in Parkinson’s disease: PET [18F]6-L-fluorodopa studies in two patients with putaminal implants. Ann Neurol. 1992;31(2):166–73.

Lindvall O, Widner H, Rehncrona S, Brundin P, Odin P, Gustavii B, et al. Transplantation of fetal dopamine neurons in Parkinson’s disease: one-year clinical and neurophysiological observations in two patients with putaminal implants. Ann Neurol. 1992;31(2):155–65.

Lindvall O, Rehncrona S, Brundin P, Gustavii B, Astedt B, Widner H, et al. Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson’s disease. A detailed account of methodology and a 6-month follow-up. Arch Neurol. 1989;46(6):615–31.

Lindvall O, Rehncrona S, Gustavii B, Brundin P, Astedt B, Widner H, et al. Fetal dopamine-rich mesencephalic grafts in Parkinson’s disease. Lancet. 1988;2(8626–8627):1483–4.

Schumacher JM, Ellias SA, Palmer EP, Kott HS, Dinsmore J, Dempsey PK, et al. Transplantation of embryonic porcine mesencephalic tissue in patients with PD. Neurology. 2000;54(5):1042–50.

Fink JS, Schumacher JM, Ellias SL, Palmer EP, Saint-Hilaire M, Shannon K, et al. Porcine xenografts in Parkinson’s disease and Huntington’s disease patients: preliminary results. Cell Transplant. 2000;9(2):273–8.

Deacon T, Schumacher J, Dinsmore J, Thomas C, Palmer P, Kott S, et al. Histological evidence of fetal pig neural cell survival after transplantation into a patient with Parkinson’s disease. Nat Med. 1997;3(3):350–3.

Jacques DB, Kopyov OV, Eagle KS, Carter T, Lieberman A. Outcomes and complications of fetal tissue transplantation in Parkinson’s disease. Stereotact Funct Neurosurg. 1999;72(2–4):219–24.

Kopyov OV, Jacques DS, Lieberman A, Duma CM, Rogers RL. Outcome following intrastriatal fetal mesencephalic grafts for Parkinson’s patients is directly related to the volume of grafted tissue. Exp Neurol. 1997;146(2):536–45.

Kopyov OV, Jacques D, Lieberman A, Duma CM, Rogers RL. Clinical study of fetal mesencephalic intracerebral transplants for the treatment of Parkinson’s disease. Cell Transplant. 1996;5(2):327–37.

Defer GL, Geny C, Ricolfi F, Fenelon G, Monfort JC, Remy P, et al. Long-term outcome of unilaterally transplanted parkinsonian patients. I Clinical approach. Brain. 1996;119(1):41–50.

Remy P, Samson Y, Hantraye P, Fontaine A, Defer G, Mangin JF, et al. Clinical correlates of [18F]fluorodopa uptake in five grafted parkinsonian patients. Ann Neurol. 1995;38(4):580–8.

Peschanski M, Defer G, N’Guyen JP, Ricolfi F, Monfort JC, Remy P, et al. Bilateral motor improvement and alteration of L-dopa effect in two patients with Parkinson’s disease following intrastriatal transplantation of foetal ventral mesencephalon. Brain. 1994;117(3):487–99.

Sass KJ, Buchanan CP, Westerveld M, Marek KL, Farhi A, Robbins RJ, et al. General cognitive ability following unilateral and bilateral fetal ventral mesencephalic tissue transplantation for treatment of Parkinson’s disease. Arch Neurol. 1995;52(7):680–6.

Price LH, Spencer DD, Marek KL, Robbins RJ, Leranth C, Farhi A, et al. Psychiatric status after human fetal mesencephalic tissue transplantation in Parkinson’s disease. Biol Psychiatry. 1995;38(8):498–505.

Spencer DD, Robbins RJ, Naftolin F, Marek KL, Vollmer T, Leranth C, et al. Unilateral transplantation of human fetal mesencephalic tissue into the caudate nucleus of patients with Parkinson’s disease. N Engl J Med. 1992;327(22):1541–8.

Henderson B, Good PA, Hitchcock ER, Clough CG, Hughes RC, Kenny BG. Visual evoked cortical responses and electroretinograms following implantation of human fetal mesencephalon to the right caudate nucleus in Parkinson’s disease. J Neurol Sci. 1992;107(2):183–90.

Henderson BT, Clough CG, Hughes RC, Hitchcock ER, Kenny BG. Implantation of human fetal ventral mesencephalon to the right caudate nucleus in advanced Parkinson’s disease. Arch Neurol. 1991;48(8):822–7.

Hitchcock ER, Kenny BG, Clough CG, Hughes RC, Henderson BT, Detta A. Stereotactic implantation of foetal mesencephalon (STIM): the UK experience. Prog Brain Res. 1990;82:723–8.

Hitchcock ER, Clough C, Hughes R, Kenny B. Embryos and Parkinson’s disease. Lancet. 1988;1(8597):1274.

Hauser RA, Freeman TB, Snow BJ, Nauert M, Gauger L, Kordower JH, et al. Long-term evaluation of bilateral fetal nigral transplantation in Parkinson disease. Arch Neurol. 1999;56(2):179–87.

Freeman TB, Olanow CW, Hauser RA, Nauert GM, Smith DA, Borlongan CV, et al. Bilateral fetal nigral transplantation into the postcommissural putamen in Parkinson’s disease. Ann Neurol. 1995;38(3):379–88.

Kordower JH, Rosenstein JM, Collier TJ, Burke MA, Chen EY, Li JM, et al. Functional fetal nigral grafts in a patient with Parkinson’s disease: chemoanatomic, ultrastructural, and metabolic studies. J Comp Neurol. 1996;370(2):203–30.

Kordower JH, Freeman TB, Snow BJ, Vingerhoets FJ, Mufson EJ, Sanberg PR, et al. Neuropathological evidence of graft survival and striatal reinnervation after the transplantation of fetal mesencephalic tissue in a patient with Parkinson’s disease. N Engl J Med. 1995;332(17):1118–24.

Barker RA. Designing stem-cell-based dopamine cell replacement trials for Parkinson’s disease. Nat Med. 2019;25(7):1045–53.

Li JY, Englund E, Widner H, Rehncrona S, Björklund A, Lindvall O, et al. Characterization of Lewy body pathology in 12- and 16-year-old intrastriatal mesencephalic grafts surviving in a patient with Parkinson’s disease. Mov Disord. 2010;25(8):1091–6.

Kordower JH, Chu Y, Hauser RA, Freeman TB, Olanow CW. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson’s disease. Nat Med. 2008;14(5):504–6.

Kordower JH, Chu Y, Hauser RA, Olanow CW, Freeman TB. Transplanted dopaminergic neurons develop PD pathologic changes: a second case report. Mov Disord. 2008;23(16):2303–6.

Li JY, Englund E, Holton JL, Soulet D, Hagell P, Lees AJ, et al. Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nat Med. 2008;14(5):501–3.

Mendez I, Viñuela A, Astradsson A, Mukhida K, Hallett P, Robertson H, et al. Dopamine neurons implanted into people with Parkinson’s disease survive without pathology for 14 years. Nat Med. 2008;14(5):507–9.

Cochen V, Ribeiro MJ, Nguyen JP, Gurruchaga JM, Villafane G, Loc’h C, et al. Transplantation in Parkinson’s disease: PET changes correlate with the amount of grafted tissue. Mov Disord. 2003;18(8):928–32.

Wu C, Liu Y, Wang J, Yang Y, Jiang Y. Intracerebral transplantation of nerve cells and genetically modified cells for disorders of central nervous system, a basic and clinical study. Zhonghua Yi Xue Za Zhi. 2002;82(7):440–4.

Mendez I, Dagher A, Hong M, Hebb A, Gaudet P, Law A, et al. Enhancement of survival of stored dopaminergic cells and promotion of graft survival by exposure of human fetal nigral tissue to glial cell line--derived neurotrophic factor in patients with Parkinson’s disease. Report of two cases and technical considerations. J Neurosurg. 2000;92(5):863–9.

Ross BD, Hoang TQ, Blüml S, Dubowitz D, Kopyov OV, Jacques DB, et al. In vivo magnetic resonance spectroscopy of human fetal neural transplants. NMR Biomed. 1999;12(4):221–36.

Piccini P, Brooks DJ, Björklund A, Gunn RN, Grasby PM, Rimoldi O, et al. Dopamine release from nigral transplants visualized in vivo in a Parkinson’s patient. Nat Neurosci. 1999;2(12):1137–40.

Kordower JH, Freeman TB, Chen EY, Mufson EJ, Sanberg PR, Hauser RA, et al. Fetal nigral grafts survive and mediate clinical benefit in a patient with Parkinson’s disease. Mov Disord. 1998;13(3):383–93.

Mamelak AN, Eggerding FA, Oh DS, Wilson E, Davis RL, Spitzer R, et al. Fatal cyst formation after fetal mesencephalic allograft transplant for Parkinson’s disease. J Neurosurg. 1998;89(4):592–8.

Levivier M, Dethy S, Rodesch F, Peschanski M, Vandesteene A, David P, et al. Intracerebral transplantation of fetal ventral mesencephalon for patients with advanced Parkinson’s disease. Methodology and 6-month to 1-year follow-up in 3 patients. Stereotact Funct Neurosurg. 1997;69(2):99–111.

López-Lozano JJ, Bravo G, Brera B, Millán I, Dargallo J, Salmeán J, et al. Long-term improvement in patients with severe Parkinson’s disease after implantation of fetal ventral mesencephalic tissue in a cavity of the caudate nucleus: 5-year follow up in 10 patients. Clinica Puerta de Hierro Neural Transplantation Group. J Neurosurg. 1997;86(6):931–42.

Baker KK, Ramig LO, Johnson AB, Freed CR. Preliminary voice and speech analysis following fetal dopamine transplants in 5 individuals with Parkinson disease. J Speech Lang Hear Res. 1997;40(3):615–26.

Folkerth RD, Durso R. Survival and proliferation of nonneural tissues, with obstruction of cerebral ventricles, in a parkinsonian patient treated with fetal allografts. Neurology. 1996;46(5):1219–25.

Ząbek M, Mazurowski W, Dymecki J, Stelmachów J, Zawada E. A long term follow-up of fetal dopaminergic neurons transplantation into the brain of three parkinsonian patients. Restor Neurol Neurosci. 1994;6(2):97–106.

Markham CM, Rand RW, Jacques DB, Diamond SG, Kopyov OV, Snow B. Transplantation of fetal mesencephalic tissue in Parkinson’s patients. Stereotact Funct Neurosurg. 1994;62(1–4):134–40.

Molina H, Quiñones R, Ortega I, Alvarez L, Muñoz J, Gonzalez C, et al. Computer assisted CT-guided stereotactic transplantation of foetal ventral mesencephalon to the caudate nucleus and putamen in Parkinson’s disease. Acta Neurochir Suppl (Wien). 1993;58:17–9.

Freed CR, Breeze RE, Rosenberg NL, Schneck SA, Kriek E, Qi JX, et al. Survival of implanted fetal dopamine cells and neurologic improvement 12 to 46 months after transplantation for Parkinson’s disease. N Engl J Med. 1992;327(22):1549–55.

Lindvall O, Brundin P, Widner H, Rehncrona S, Gustavii B, Frackowiak R, et al. Grafts of fetal dopamine neurons survive and improve motor function in Parkinson’s disease. Science. 1990;247(4942):574–7.

Freed CR, Breeze RE, Rosenberg NL, Schneck SA, Wells TH, Barrett JN, et al. Transplantation of human fetal dopamine cells for Parkinson’s disease. Results at 1 year. Arch Neurol. 1990;47(5):505–12.

Madrazo I, León V, Torres C, Aguilera MC, Varela G, Alvarez F, et al. Transplantation of fetal substantia nigra and adrenal medulla to the caudate nucleus in two patients with Parkinson’s disease. N Engl J Med. 1988;318(1):51.

Porena M, Parziani S, Costantini E, Vespasiani G, Micali F. Autologous adrenal medullary transplant in Parkinson’s disease: critical review of our results in 13 patients. Neurourol Urodyn. 1996;15(3):195–201.

Sydow O, Hansson P, Young D, Meyerson B, Backlund EO, Ebendal T, et al. Long-term beneficial effects of adrenal medullary autografts supported by nerve growth factor in Parkinson’s disease. Eur J Neurol. 1995;2(5):445–54.

Diamond SG, Markham CH, Rand RW, Becker DP, Treciokas LJ. Four-year follow-up of adrenal-to-brain transplants in Parkinson’s disease. Arch Neurol. 1994;51(6):559–63.

Goetz CG, Stebbins GT 3rd, Klawans HL, Koller WC, Grossman RG, Bakay RA, et al. United Parkinson Foundation Neurotransplantation Registry on adrenal medullary transplants: presurgical, and 1- and 2-year follow-up. Neurology. 1991;41(11):1719–22.

Jimenez F, Velasco F, Velasco M, Velasco AL. Long-term effects of medical and surgical treatments on Parkinson’s disease. Stereotact Funct Neurosurg. 1994;62(1–4):85–9.

Madrazo I, Franco-Bourland R, Aguilera M, Ostrosky-Solis F, Madrazo M, Cuevas C, et al. Autologous adrenal medullary, fetal mesencephalic, and fetal adrenal brain transplantation in Parkinson’s disease: a long-term postoperative follow-up. J Neural Transplant Plast. 1991;2(3–4):157–64.

Velasco F, Velasco M, Rodríguez Cuevas H, Jurado J, Olvera J, Jiménez F. Autologous adrenal medullary transplants in advanced Parkinson’s disease with particular attention to the selective improvement in symptoms. Stereotact Funct Neurosurg. 1991;57(4):195–212.

Olson L, Backlund EO, Ebendal T, Freedman R, Hamberger B, Hansson P, et al. Intraputaminal infusion of nerve growth factor to support adrenal medullary autografts in Parkinson’s disease. One-year follow-up of first clinical trial. Arch Neurol. 1991;48(4):373–81.

Kordower JH, Cochran E, Penn RD, Goetz CG. Putative chromaffin cell survival and enhanced host-derived TH-fiber innervation following a functional adrenal medulla autograft for Parkinson’s disease. Ann Neurol. 1991;29(4):405–12.

López-Lozano JJ, Bravo G, Abascal J. Grafting of perfused adrenal medullary tissue into the caudate nucleus of patients with Parkinson’s disease. Clinica Puerta de Hierro Neural Transplantation Group. J Neurosurg. 1991;75(2):234–43.

Skinner EC, Boyd SD, Apuzzo ML. Technique of left adrenalectomy for autotransplantation to the caudate nucleus in Parkinson’s disease. J Urol. 1990;144(4):838–41.

Goetz CG, Olanow CW, Koller WC, Penn RD, Cahill D, Morantz R, et al. Multicenter study of autologous adrenal medullary transplantation to the corpus striatum in patients with advanced Parkinson’s disease. N Engl J Med. 1989;320(6):337–41.

Penn RD, Goetz CG, Tanner CM, Klawans HL, Shannon KM, Comella CL, et al. The adrenal medullary transplant operation for Parkinson’s disease: clinical observations in five patients. Neurosurgery. 1988;22(1):999–1004.

Lindvall O, Backlund EO, Farde L, Sedvall G, Freedman R, Hoffer B, et al. Transplantation in Parkinson’s disease: two cases of adrenal medullary grafts to the putamen. Ann Neurol. 1987;22(4):457–68.

Madrazo I, Drucker-Colín R, Díaz V, Martínez-Mata J, Torres C, Becerril JJ. Open microsurgical autograft of adrenal medulla to the right caudate nucleus in two patients with intractable Parkinson’s disease. N Engl J Med. 1987;316(14):831–4.

Backlund EO, Granberg PO, Hamberger B, Knutsson E, Mårtensson A, Sedvall G, et al. Transplantation of adrenal medullary tissue to striatum in parkinsonism. First clinical trials. J Neurosurg. 1985;62(2):169–73.

Mínguez-Castellanos A, Escamilla-Sevilla F, Hotton GR, Toledo-Aral JJ, Ortega-Moreno A, Méndez-Ferrer S, et al. Carotid body autotransplantation in Parkinson disease: a clinical and positron emission tomography study. J Neurol Neurosurg Psychiatry. 2007;78(8):825–31.

Arjona V, Mínguez-Castellanos A, Montoro RJ, Ortega A, Escamilla F, Toledo-Aral JJ, et al. Autotransplantation of human carotid body cell aggregates for treatment of Parkinson’s disease. Neurosurgery. 2003;53(2):321–30.

Nakao N, Kakishita K, Uematsu Y, Yoshimasu T, Bessho T, Nakai K, et al. Enhancement of the response to levodopa therapy after intrastriatal transplantation of autologous sympathetic neurons in patients with Parkinson disease. J Neurosurg. 2001;95(2):275–84.

Nakao N, Shintani-Mizushima A, Kakishita K, Itakura T. The ability of grafted human sympathetic neurons to synthesize and store dopamine: a potential mechanism for the clinical effect of sympathetic neuron autografts in patients with Parkinson’s disease. Exp Neurol. 2004;188(1):65–73.

Itakura T, Uematsu Y, Nakao N, Nakai E, Nakai K. Transplantation of autologous sympathetic ganglion into the brain with Parkinson’s disease. Long-term follow-up of 35 cases. Stereotact Funct Neurosurg. 1997;69(2):112–5.

Itakura T, Nakai M, Nakao N, Ooiwa Y, Uematsu Y, Komai N. Transplantation of autologous cervical sympathetic ganglion into the brain with Parkinson’s disease: experimental and clinical studies. Cell Transplant. 1994;3(Suppl 1):43–5.

Carstens M, Haq I, Martinez-Cerrato J, Dos-Anjos S, Bertram K, Correa D. Sustained clinical improvement of Parkinson’s disease in two patients with facially-transplanted adipose-derived stromal vascular fraction cells. J Clin Neurosci. 2020;81:47–51.

Schiess M, Suescun J, Doursout MF, Adams C, Green C, Saltarrelli JG, et al. Allogeneic bone marrow-derived mesenchymal stem cell safety in idiopathic Parkinson’s disease. Mov Disord. 2021;36(8):1825–34.

Venkataramana NK, Pal R, Rao SA, Naik AL, Jan M, Nair R, et al. Bilateral transplantation of allogenic adult human bone marrow-derived mesenchymal stem cells into the subventricular zone of Parkinson’s disease: a pilot clinical study. Stem Cells Int. 2012;2012:931902.

Boika A, Aleinikava N, Chyzhyk V, Zafranskaya M, Nizheharodava D, Ponomarev V. Mesenchymal stem cells in Parkinson’s disease: motor and nonmotor symptoms in the early posttransplant period. Surg Neurol Int. 2020;11:380.

Storch A, Csoti I, Eggert K, Henriksen T, Plate A, Lorrain M, et al. Intrathecal application of autologous bone marrow cell preparations in Parkinsonian syndromes. Mov Disord. 2012;27(12):1552–5.

Brazzini A, Cantella R, De la Cruz A, Yupanqui J, León C, Jorquiera T, et al. Intraarterial autologous implantation of adult stem cells for patients with Parkinson disease. J Vasc Interv Radiol. 2010;21(4):443–51.

Madrazo I, Kopyov O, Ávila-Rodríguez MA, Ostrosky F, Carrasco H, Kopyov A, et al. Transplantation of human neural progenitor cells (NPC) into putamina of parkinsonian patients: a case series study, safety and efficacy four years after surgery. Cell Transplant. 2019;28(3):269–85.

Lige L, Zengmin T. Transplantation of neural precursor cells in the treatment of parkinson disease: an efficacy and safety analysis. Turk Neurosurg. 2016;26(3):378–83.

Sinelnyk A, Sych N, Klunnyk M, Demchuk M, Ivankova O. Non-motor symptoms in Parkinson’s disease and efficacy of treatment in a complex therapy using fetal stem cells. J Stem Cell Res Ther. 2015;5(300):2.

Yin F, Tian ZM, Liu S, Zhao QJ, Wang RM, Shen L, et al. Transplantation of human retinal pigment epithelium cells in the treatment for Parkinson disease. CNS Neurosci Ther. 2012;18(12):1012–20.

Gross RE, Watts RL, Hauser RA, Bakay RA, Reichmann H, von Kummer R, et al. Intrastriatal transplantation of microcarrier-bound human retinal pigment epithelial cells versus sham surgery in patients with advanced Parkinson’s disease: a double-blind, randomised, controlled trial. Lancet Neurol. 2011;10(6):509–19.

Stover NP, Bakay RAE, Subramanian T, Raiser CD, Cornfeldt ML, Schweikert AW, et al. Intrastriatal implantation of human retinal pigment epithelial cells attached to microcarriers in advanced Parkinson disease. Arch Neurol. 2005;62(12):1833–7.

Bakay RA, Raiser CD, Stover NP, Subramanian T, Cornfeldt ML, Schweikert AW, et al. Implantation of Spheramine in advanced Parkinson’s disease (PD). Front Biosci. 2004;9:592–602.

Venkataramana NK, Kumar SK, Balaraju S, Radhakrishnan RC, Bansal A, Dixit A, et al. Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson’s disease. Transl Res. 2010;155(2):62–70.

Snow B, Mulroy E, Bok A, Simpson M, Smith A, Taylor K, et al. A phase IIb, randomised, double-blind, placebo-controlled, dose-ranging investigation of the safety and efficacy of NTCELL(®) [immunoprotected (alginate-encapsulated) porcine choroid plexus cells for xenotransplantation] in patients with Parkinson’s disease. Parkinsonism Relat Disord. 2019;61:88–93.

Mulroy E, Snow B, Bok A, Simpson M, Smith A, Taylor KM, et al. A long-term follow-up of safety and clinical efficacy of NTCELL® [immunoprotected (alginate-encapsulated) porcine choroid plexus cells for xenotransplantation] in patients with Parkinson’s disease. Parkinsonism Relat Disord. 2021;82:128–32.

Farag ES, Vinters HV, Bronstein J. Pathologic findings in retinal pigment epithelial cell implantation for Parkinson disease. Neurology. 2009;73(14):1095–102.

Peterson DI, Price ML, Small CS. Autopsy findings in a patient who had an adrenal-to-brain transplant for Parkinson’s disease. Neurology. 1989;39(1):235–8.

Toledo-Aral JJ, Méndez-Ferrer S, Pardal R, Echevarría M, López-Barneo J. Trophic restoration of the nigrostriatal dopaminergic pathway in long-term carotid body-grafted parkinsonian rats. J Neurosci. 2003;23(1):141–8.

Perlow MJ, Freed WJ, Hoffer BJ, Seiger A, Olson L, Wyatt RJ. Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system. Science. 1979;204(4393):643–7.

Björklund A, Stenevi U. Reconstruction of the nigrostriatal dopamine pathway by intracerebral nigral transplants. Brain Res. 1979;177(3):555–60.

Hallett PJ, Cooper O, Sadi D, Robertson H, Mendez I, Isacson O. Long-term health of dopaminergic neuron transplants in Parkinson’s disease patients. Cell Rep. 2014;7(6):1755–61.

Li W, Englund E, Widner H, Mattsson B, van Westen D, Lätt J, et al. Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain. Proc Natl Acad Sci U S A. 2016;113(23):6544–9.

Mendez I, Sanchez-Pernaute R, Cooper O, Viñuela A, Ferrari D, Björklund L, et al. Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson’s disease. Brain. 2005;128(7):1498–510.

Wei M, Li S, Yang Z, Cheng C, Li T, Le W. Tetrahedral DNA nanostructures functionalized by multivalent microRNA132 antisense oligonucleotides promote the differentiation of mouse embryonic stem cells into dopaminergic neurons. Nanomedicine. 2021;34:102375.

Wei M, Li S, Yang Z, Zheng W, Le W. Gold nanoparticles enhance the differentiation of embryonic stem cells into dopaminergic neurons via mTOR/p70S6K pathway. Nanomedicine (Lond). 2017;12(11):1305–17.

Yang D, Li T, Xu M, Gao F, Yang J, Yang Z, et al. Graphene oxide promotes the differentiation of mouse embryonic stem cells to dopamine neurons. Nanomedicine (Lond). 2014;9(16):2445–55.

Movement Disorder Society Task Force on Rating Scales for Parkinson's Disease. The Unified Parkinson's Disease Rating Scale (UPDRS): status and recommendations. Mov Disord. 2003;18(7):738–50.

Piccini P, Pavese N, Hagell P, Reimer J, Björklund A, Oertel WH, et al. Factors affecting the clinical outcome after neural transplantation in Parkinson’s disease. Brain. 2005;128(12):2977–86.

Freed CR, Breeze RE, Fahn S, Eidelberg D. Preoperative response to levodopa is the best predictor of transplant outcome. Ann Neurol. 2004;55(6):896–7.

Li S, Oh BC, Chu C, Arnold A, Jablonska A, Furtmüller GJ, et al. Induction of immunological tolerance to myelinogenic glial-restricted progenitor allografts. Brain. 2019;142(11):3456–72.

Lane EL, Vercammen L, Cenci MA, Brundin P. Priming for L-DOPA-induced abnormal involuntary movements increases the severity of amphetamine-induced dyskinesia in grafted rats. Exp Neurol. 2009;219(1):355–8.

Carlsson T, Winkler C, Lundblad M, Cenci MA, Björklund A, Kirik D. Graft placement and uneven pattern of reinnervation in the striatum is important for development of graft-induced dyskinesia. Neurobiol Dis. 2006;21(3):657–68.

Maries E, Kordower JH, Chu Y, Collier TJ, Sortwell CE, Olaru E, et al. Focal not widespread grafts induce novel dyskinetic behavior in parkinsonian rats. Neurobiol Dis. 2006;21(1):165–80.

Carlsson T, Carta M, Winkler C, Björklund A, Kirik D. Serotonin neuron transplants exacerbate L-DOPA-induced dyskinesias in a rat model of Parkinson’s disease. J Neurosci. 2007;27(30):8011–22.

Politis M, Wu K, Loane C, Quinn NP, Brooks DJ, Rehncrona S, et al. Serotonergic neurons mediate dyskinesia side effects in Parkinson’s patients with neural transplants. Sci Transl Med. 2010;2(38):38ra46.

Politis M, Oertel WH, Wu K, Quinn NP, Pogarell O, Brooks DJ, et al. Graft-induced dyskinesias in Parkinson’s disease: high striatal serotonin/dopamine transporter ratio. Mov Disord. 2011;26(11):1997–2003.

Politis M, Wu K, Loane C, Kiferle L, Molloy S, Brooks DJ, et al. Staging of serotonergic dysfunction in Parkinson’s disease: an in vivo 11C-DASB PET study. Neurobiol Dis. 2010;40(1):216–21.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (82171319) and Central Committee Healthcare Project (2020YB64).

Author information

Fang Wang, Zhengwu Sun, Daoyong Peng contributed equally to this study.

Authors and Affiliations

Department of Neurology, Central Hospital of Dalian University of Technology, Dalian, China

Fang Wang & Daoyong Peng

Department of Clinical Pharmacy, Central Hospital of Dalian University of Technology, Dalian, China

Zhengwu Sun

School of Life Sciences, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK

Shikha Gianchandani & Johannes Boltze

Institute of Neurology, Sichuan Academy of Medical Sciences, Sichuan Provincial Hospital, Chengdu, China

Department of Neurology and Psychiatry, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Beijing, 100038, China

Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China

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FW, ZWS, DYP, and SL had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. JB and SL conceived and designed the study. FW, ZWS, DYP, and SL undertook the statistical analyses. FW, ZWS, and DYP made figures. All authors advised on statistical analyses and visualization. FW and ZWS wrote the first draft of the manuscript. All authors made critical revisions of the manuscript for important intellectual content. All authors have read and approved the final version of the manuscript.

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Correspondence to Shen Li .

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Supplementary Information

Additional file 1: fig. s1.

. UPDRS or UPDRSIII scores pre- versus post-transplantation in ‘on’ or ‘off’ state at the last follow-up. Nine studies are included. Random-effect model is used. The sizes of squares represent the weight that each study contributes. The diamond at the bottom represents the overall effect. CI = confidence interval (represented by the lines).

Additional file 2: Fig. S2

. UPDRS score pre- versus post-transplantation in the ‘on’ state at the last follow-up, or at 12-, 24-, and ≥ 36-month follow-ups. The number of studies included are 4, 3, 2, and 2, respectively. If the I 2 value is less than 30%, a fixed-effect model is used. If the I 2 value is greater than 30%, a random-effect model is used. The sizes of squares represent the weight that each study contributes. The diamond at the bottom represents the overall effect. CI = confidence interval (represented by the lines).

Additional file 3: Fig. S3

. H-Y score pre- versus post-transplantation in the ‘on’ or ‘off’ states at the last follow-up. Four studies are included. Random-effect model is used. The sizes of squares represent the weight that each study contributes. The diamond at the bottom represents the overall effect. CI = confidence interval (represented by the lines).

Additional file 4: Fig. S4

. UPDRSIII score pre- versus post-transplantation in the ‘off’ state at 48-month follow-up. Two studies are included. Fixed-effect model is used. The sizes of squares represent the weight that each study contributes. The diamond at the bottom represents the overall effect. CI = confidence interval (represented by the lines).

Additional file 5: Fig. S5

. Beck Depression inventory score pre- versus post-transplantation in the ‘on’ or ‘off’ states at the last follow-up. Three studies are included. Random-effect model is used. The sizes of squares represent the weight that each study contributes. The diamond at the bottom represents the overall effect. CI = confidence interval (represented by the lines).

Additional file 6: Fig. S6

. UPDRS, UPDRSIII and UPDRSII scores pre- versus post-transplantation in the ‘off’ and ‘on’ states at the last follow-ups after allogeneic cell treatment. The number of studies included are 6, 6, 4, 3, 3, and 3, respectively. If the I 2 value is less than 30%, a fixed-effect model is used. If the I 2 value is greater than 30%, a random-effect model is used. The sizes of squares represent the weight that each study contributes. The diamond at the bottom represents the overall effect. CI = confidence interval (represented by the lines).

Additional file 7: Fig. S7

. H-Y score pre- versus post-transplantation in the ‘on’ or ‘off’ states at the last follow-up after autologous cell treatment. Two studies are included. Random-effect model is used. The sizes of squares represent the weight that each study contributes. The diamond at the bottom represents the overall effect. CI = confidence interval (represented by the lines).

Additional file 8: Fig. S8

. Funnel plots assessing potential publication bias on homogeneous cell transplantation in PD treatment. (a) UPDRS or UPDRSIII scores pre- versus post-transplantation in ‘on’ or ‘off’ state at the last follow-up. (b) UPDRS score pre- versus post-transplantation in the ‘off’ state at last follow-up. (c) UPDRSIII score pre- versus post-transplantation in the ‘off’ state at last follow-up. (d) UPDRSIII scores pre- versus post-transplantation in the ‘off’ states at the last follow-up with levodopa responders. (e) UPDRS scores pre- versus post-transplantation in the ‘off’ states after allogeneic cell treatment. (f) UPDRSIII scores pre- versus post-transplantation in the ‘off’ states at the last follow-ups after allogeneic cell treatment. Each dot represents a single study. The dashed vertical line represents the pooled effect size. The dashed diagonal lines represent 95% confidence limits around the pooled effect size for each standard error on the vertical axis, and are only provided in plots when fixed effect models were used.

Additional file 9: Table S1

. Fetal mesencephalic tissue transplantation: characteristics of the studies and subjects.

Additional file 10: Table S2

. Adrenal medulla transplantation: characteristics of the studies and subjects.

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Wang, F., Sun, Z., Peng, D. et al. Cell-therapy for Parkinson’s disease: a systematic review and meta-analysis. J Transl Med 21 , 601 (2023). https://doi.org/10.1186/s12967-023-04484-x

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