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Systematic Reviews Classes

Systematic reviews are a complex undertaking and involves multiple steps in order to produce a quality systematic review. Our classes will provide an introduction to different types of systematic reviews, the overall review process, what a comprehensive literature search entails, development of a protocol, identification of screening criteria, suggestions for data collection and management, appropriate standards and guidelines to follow, and suggestions on how to write up your review for journal submission. The list below includes Systematic Review classes in our course catalog. Click the title of the class to view any upcoming sessions.

Collecting and Cleaning Data for Your Review

  • Read more about Collecting and Cleaning Data for Your Review

This class will provide an overview of the data collection process for your review – whether scoping or systematic. The importance of data cleaning for consistency to ensure accurate identification of comparable outcome measures across studies and how to do so will be discussed. We will review the process and tools to use, discuss recommended practices, and share lessons learned. Participants will receive resources and information on recommended practices for performing this important step in your review.

Conducting the Screening and Risk of Bias Steps in Your Review

  • Read more about Conducting the Screening and Risk of Bias Steps in Your Review

This class will provide a comprehensive look into critical steps of the review process – establishing your inclusion and exclusion criteria and then using those criteria to conduct the screening steps to select relevant studies for your review. We will discuss completing the risk of bias assessment, a key feature of systematic reviews. Participants will receive resources and information on best practice for performing these steps to facilitate an effective and rigorous review.

Developing and Publishing Your Review Protocol

  • Read more about Developing and Publishing Your Review Protocol

This class is a part of the systematic reviews class series. Systematic and scoping reviews are a complex undertaking and involve multiple steps in order to produce a quality review. Developing a protocol to guide the conduct of your review is a critical step. This class explains what a review protocol is, how to develop one, and how to use it for the conduct of your review. Resources to develop the protocol and where to register or publish it will be shared.

Developing the Research Question and Conducting the Literature Search

  • Read more about Developing the Research Question and Conducting the Literature Search

This session focuses on defining the scope of your review by applying techniques to formulate a workable research question. The class introduces various frameworks used for developing a research question, and presents the requirements and steps involved in conducting the literature search for the systematic review. Useful resources are introduced throughout the session.

Exploring the Cochrane Library: Systematic Reviews, Clinical Trials, and More

  • Read more about Exploring the Cochrane Library: Systematic Reviews, Clinical Trials, and More

Cochrane Library is a collection of databases with high-quality systematic reviews, randomized controlled trials and clinical answers. It offers simultaneous search of variety of resources to provide independent evidence to inform healthcare professionals in their decision making. This class will introduce the variety of resources offered by Cochrane Library, how to search them, and the key features of the search platform.

Foundations of Literature Searching

  • Read more about Foundations of Literature Searching

This class will explore best practices for planning and conducting literature searches. The topics and tips introduced in this session are intended to support general literature searching practices that participants can use to conduct more effective searches, regardless of database used. This class will address the importance of the literature search, introduce a basic framework to help develop search strategies, discuss how to connect concepts and use other search helpers in your strategies, and explore resources and tools that support good literature searching practices. 

Gray Literature: Searching Beyond the Databases

  • Read more about Gray Literature: Searching Beyond the Databases

Gray literature is not controlled by commercial publishers and usually is not peer reviewed. However, gray literature can help identify useful information outside the published, peer reviewed articles through reports, dissertations, conference abstracts, official documents, research-in-progress, and clinical trials. It might get you information you would never find in traditional sources. This workshop will focus on how to find credible gray literature for your research topic or for part of a systematic review.

Introduction to Rapid Reviews

  • Read more about Introduction to Rapid Reviews

During the COVID-19 pandemic, the number of rapid reviews increased and became a popular method of conducting a rigorous literature review, using systematic review methodology in a shorter time frame. This type of review helps synthesize the available evidence in a narrative descriptive format and can be done at a faster pace than a full systematic review. The introductory class will discuss what research questions are best suited for a rapid review, best practices for their conduct, and review the required methodological steps on how to conduct an effective rapid review. 

Introduction to Scoping Reviews

  • Read more about Introduction to Scoping Reviews

A scoping review is a preliminary assessment of research literature that aims to systematically map the literature, clarify concepts, and identify the evidence and knowledge gaps on a topic. This research method can be conducted as standalone review or used as an initial step before conducting a full systematic review. Participants will learn best practices, tips, and guidelines on how to conduct a scoping review. This introductory class will also include scoping review resources and an overview of NIH Library research support services.

Introduction to the Systematic Review Process

  • Read more about Introduction to the Systematic Review Process

Conducting a systematic review can be time consuming and challenging. This class provides an overview of the different steps in the comprehensive process of conducting a systematic review. At the completion of the class, participants will be able to identify each step of the systematic review process and know where to access valuable resources.

Introduction to Umbrella Reviews: Conducting a Review of Reviews

  • Read more about Introduction to Umbrella Reviews: Conducting a Review of Reviews

Umbrella reviews, sometimes referred to as review of reviews, are a review of other published systematic reviews and meta-analyses and are appearing more frequently in scientific literature. Umbrella reviews appropriately address a broad question on a topic when there are plenty of published reviews already available. The benefits of conducting an umbrella review are to help synthesize the evidence for decision making in healthcare and explore inconsistencies and biases.

Literature Reviews: Select the Right Type

  • Read more about Literature Reviews: Select the Right Type

You aren’t sure which type of literature review would best match your research question, or maybe you didn’t realize there were so many kinds of reviews. Join us for an overview of literature review types and their purposes. By the end of this session, attendees will be able to describe the purpose of a literature review, differentiate among five types, and select the right review for your research goals.

Meta-Analysis: Quantifying a Systematic Review

  • Read more about Meta-Analysis: Quantifying a Systematic Review

The purpose of this class is to introduce the fundamentals of conducting a meta-analysis. The focus will be on randomized clinical trials; however, the presenter will also briefly discuss the application of meta-analyses in laboratory and observational (epidemiological) studies. 

Retractions in Evidence Synthesis

  • Read more about Retractions in Evidence Synthesis

This class will define retractions and discuss their effects on evidence synthesis products such as systematic reviews. Participants will explore the impact and consequences of retractions through a case study along with data from the literature. Additionally, participants will learn about how to incorporate identification of retractions into the evidence synthesis process. This class is recommended for anyone who wants a more in-depth analysis of retractions beyond what is covered in the Retractions: An Introduction class.

Selecting the Most Appropriate Type of Literature Review for Your Research

  • Read more about Selecting the Most Appropriate Type of Literature Review for Your Research

Do you want to write a review, but not sure what type of review would be best for your research question or topic? In today’s research environment, everyone seems to be doing a review of some type, especially systematic reviews.  However, not all literature reviews are systematic reviews, nor need to be. There are many other types of evidence-based reviews. This session will explore the various literature review types, the associated methodologies of each, and how to select the best option for you.

Using Covidence for Conducting Your Review

  • Read more about Using Covidence for Conducting Your Review

Covidence is a web-based tool that can be used in conducting systematic and scoping reviews, and meta-analyses. This tool helps researchers manage article screening at the title, abstract, and full text levels. This class covers the basic features of Covidence, including setting up a review, importing and exporting records, and screening. Data extraction, quality assessment, and additional resources will be covered. At least one member of the research team must be based at the NIH to gain Covidence access.

Writing and Publishing Your Review

  • Read more about Writing and Publishing Your Review

This class will provide an overview of the various reporting guidelines and standards established for conducting reviews and how to use them in the writing of your review manuscript. Participants will also gain valuable information about how to structure their manuscript and select appropriate journals for submission.

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Cochrane Cochrane Interactive Learning

Cochrane interactive learning.

Welcome to Cochrane Interactive Learning

Welcome to Cochrane Interactive Learning: Conducting an Intervention Review

New users and subscribers

Module 1: Introduction to conducting systematic reviews

Module 2: Writing the review protocol

Module 2: Writing the review protocol

Module 3:  Searching for studies

Module 3: Searching for studies

Module 4: Selecting studies and collecting data

Module 4: Selecting studies and collecting data

Module 5: Introduction to risk of bias

Module 5: Introduction to risk of bias

Module 6: Analysing the data

Module 6: Analysing the data

Module 7: Interpreting the findings

Module 7: Interpreting the findings

Module 8: Reporting the review

Module 8: Reporting the review

Module 9: Introduction to health economics

Module 9: Introduction to health economics

Module 10: Network meta-analysis

Module 10: Network meta-analysis

Module 11: Health equity in systematic reviews

Module 11: Health equity in systematic reviews

Module 12: Introduction to qualitative evidence synthesis

Module 12: Introduction to qualitative evidence synthesis

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systematic literature review course

Comprehensive Systematic Review Training Program

The jbi comprehensive systematic review training program is a three or five-day program depending on research needs or areas of interest. by the end of the  program participants are ready to begin a protocol for their systematic review.

The three or five-day Program prepares researchers and clinicians to develop, conduct and report robust, high quality systematic reviews of different evidence types in order to provide the strongest possible evidence to inform decision making or clinical guideline development in healthcare.

Module 1: Introduction to Evidence-based Healthcare and the Systematic Review of Evidence (day 1) 

Learn about evidence-based healthcare, creating systematic review protocols, and key material regarding searching the literature. This is a prerequisite for Modules 2 & 3. 

Module 2: The Systematic Review of Quantitative Evidence (days 2 and 3) 

Learn about common research designs such as randomised controlled trials, how to critically appraise research, identify important sources of bias in research, an introduction to commonly encountered statistics in clinical research, when and how to conduct meta-analysis. Module 1 attendance is a prerequisite for Module 2. 

Module 3: The Systematic Review of Evidence Generated by Qualitative Research, Narrative and Text (days 4 and 5) 

Learn about the importance of qualitative research in healthcare, common qualitative research designs such as phenomenology and ethnography, how to critically appraise qualitative research, identify different methods for synthesising qualitative research and learn when and how to perform a meta-synthesis of qualitative research. Module 1 attendance is a prerequisite for Module 3.

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Systematic Reviews and Meta Analysis

  • Getting Started
  • Guides and Standards
  • Review Protocols
  • Databases and Sources
  • Randomized Controlled Trials
  • Controlled Clinical Trials
  • Observational Designs
  • Tests of Diagnostic Accuracy
  • Software and Tools
  • Where do I get all those articles?
  • Collaborations
  • EPI 233/528
  • Countway Mediated Search
  • Risk of Bias (RoB)

Systematic review Q & A

What is a systematic review.

A systematic review is guided filtering and synthesis of all available evidence addressing a specific, focused research question, generally about a specific intervention or exposure. The use of standardized, systematic methods and pre-selected eligibility criteria reduce the risk of bias in identifying, selecting and analyzing relevant studies. A well-designed systematic review includes clear objectives, pre-selected criteria for identifying eligible studies, an explicit methodology, a thorough and reproducible search of the literature, an assessment of the validity or risk of bias of each included study, and a systematic synthesis, analysis and presentation of the findings of the included studies. A systematic review may include a meta-analysis.

For details about carrying out systematic reviews, see the Guides and Standards section of this guide.

Is my research topic appropriate for systematic review methods?

A systematic review is best deployed to test a specific hypothesis about a healthcare or public health intervention or exposure. By focusing on a single intervention or a few specific interventions for a particular condition, the investigator can ensure a manageable results set. Moreover, examining a single or small set of related interventions, exposures, or outcomes, will simplify the assessment of studies and the synthesis of the findings.

Systematic reviews are poor tools for hypothesis generation: for instance, to determine what interventions have been used to increase the awareness and acceptability of a vaccine or to investigate the ways that predictive analytics have been used in health care management. In the first case, we don't know what interventions to search for and so have to screen all the articles about awareness and acceptability. In the second, there is no agreed on set of methods that make up predictive analytics, and health care management is far too broad. The search will necessarily be incomplete, vague and very large all at the same time. In most cases, reviews without clearly and exactly specified populations, interventions, exposures, and outcomes will produce results sets that quickly outstrip the resources of a small team and offer no consistent way to assess and synthesize findings from the studies that are identified.

If not a systematic review, then what?

You might consider performing a scoping review . This framework allows iterative searching over a reduced number of data sources and no requirement to assess individual studies for risk of bias. The framework includes built-in mechanisms to adjust the analysis as the work progresses and more is learned about the topic. A scoping review won't help you limit the number of records you'll need to screen (broad questions lead to large results sets) but may give you means of dealing with a large set of results.

This tool can help you decide what kind of review is right for your question.

Can my student complete a systematic review during her summer project?

Probably not. Systematic reviews are a lot of work. Including creating the protocol, building and running a quality search, collecting all the papers, evaluating the studies that meet the inclusion criteria and extracting and analyzing the summary data, a well done review can require dozens to hundreds of hours of work that can span several months. Moreover, a systematic review requires subject expertise, statistical support and a librarian to help design and run the search. Be aware that librarians sometimes have queues for their search time. It may take several weeks to complete and run a search. Moreover, all guidelines for carrying out systematic reviews recommend that at least two subject experts screen the studies identified in the search. The first round of screening can consume 1 hour per screener for every 100-200 records. A systematic review is a labor-intensive team effort.

How can I know if my topic has been been reviewed already?

Before starting out on a systematic review, check to see if someone has done it already. In PubMed you can use the systematic review subset to limit to a broad group of papers that is enriched for systematic reviews. You can invoke the subset by selecting if from the Article Types filters to the left of your PubMed results, or you can append AND systematic[sb] to your search. For example:

"neoadjuvant chemotherapy" AND systematic[sb]

The systematic review subset is very noisy, however. To quickly focus on systematic reviews (knowing that you may be missing some), simply search for the word systematic in the title:

"neoadjuvant chemotherapy" AND systematic[ti]

Any PRISMA-compliant systematic review will be captured by this method since including the words "systematic review" in the title is a requirement of the PRISMA checklist. Cochrane systematic reviews do not include 'systematic' in the title, however. It's worth checking the Cochrane Database of Systematic Reviews independently.

You can also search for protocols that will indicate that another group has set out on a similar project. Many investigators will register their protocols in PROSPERO , a registry of review protocols. Other published protocols as well as Cochrane Review protocols appear in the Cochrane Methodology Register, a part of the Cochrane Library .

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  • Last Updated: Feb 14, 2024 2:47 PM
  • URL: https://guides.library.harvard.edu/meta-analysis

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Systematic Reviews Workshop

We welcome health sciences librarians with intermediate literature searching experience. Participants are expected to be familiar with boolean operators, advanced search features, controlled vocabulary, and field tags.

This workshop is accredited for 20 Medical Library Association continuing education credits. 

We offer the workshop twice each year . Both start with an asynchronous online course in Canvas, followed by live instruction — online in the fall and in-person in the spring.

Workshop details

A mix of instruction, exercises, presentations, and discussion designed to help librarians establish their systematic review expertise.

What You’ll Learn at the Systematic Reviews Workshop

Get an overview of the content and objectives.

Systematic Reviews Workshop Registration and Fees

Information on the workshop fee and how to register.

The APRA

Advance Systematic Literature Reviews

Dr. IQ

About Course

About course: A systematic literature review is a research method used to identify, evaluate, and summarize the research findings of a large number of published studies on a specific topic. It is a comprehensive and structured approach to reviewing the literature that aims to identify all relevant studies, critically appraise their quality, and synthesize their findings in a clear and transparent manner. This course is intended to provide learners with an asynchronous learning experience concentrating on the advanced levels of dealing with systematic literature reviews. The course covers cutting-edge methodology, tools, and computer-assisted techniques for doing systematic literature reviews. The main focus of the course is to work with a huge amount of research studies in minimum time through AI tools that enable literature classifications and synthesis. Working within each literature classification/cluster is also an important aspect of the course. The students will learn how easily and quickly we can learn from the literature and find existing gaps in the body of knowledge. The course’s research output can be submitted for publication in high-impact journals or included in a Ph.D. thesis. Experienced scholars and authors of highly cited impact factor research articles will teach the course. Videos lectures, Live classes, activities, and assessments are all part of this exciting course. After each class subscribers can send their work to the trainers to receive feedback and trainers will also provide support for its improvement. The course is divided into two levels: the first focuses on conducting systematic literature reviews and developing literature classifications/clusters using AI-based tools, while the second focuses on mapping literature within clusters and developing consensus on the existing body of knowledge. On weekends, there are eight live sessions, where learners can interact with trainers. All subscribers will get access to video recordings of each lesson, and after completing an assessment, the Association of Professional Researchers and Academicians UK will offer a certificate of completion.

In this course, students will also learn to work with

Paper digest

Visual literature search

Microsoft Excel

Power Query

Pivot tables and charts

Text Mining and bibliometric Software like Vosviewer, Biblioshiny R package

What Will You Learn?

Module 1: understanding basics, module 2: literature synthesis, module 3: developing literature classifications using ai, module 4: working within classifications, module 5: ai tools for systematic literature review, module 6: literature mapping and drawing consensus, module 7: finding gaps in literature.

  • Module 8: Future Recommendations

Course Content

Introduction to learning management system, live session: module 1: basic understanding, understanding systematic literature review, literature search using scopus database, live session 2, exporting records from scopus, installing biblioshiny (r package bibliometrix), working with bibliometric (r package), developing literature classifications using r package, merging literature clusters, working with in classifications using ai tools, drawing conclusion, findings gaps, module 8: writing paper, writing abstract, student ratings & reviews.

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NUS: The Art and Science of Searching in Systematic Reviews

This course is useful for anyone responsible for searching literature systematically either for a systematic review or a comprehensive literature review.

Learn the fundamentals of systematic review searching, including strategies, information sources and methods to manage & report search methods across disciplines.

systematic literature review course

There is one session available:

The art and science of searching in systematic reviews, about this course.

This course goes beyond the traditional focus of Systematic Review searching to answer clinical questions. It introduces searching methods that can be applied to a wide range of disciplines including social science, environmental science, policy studies, sciences, health sciences and more.

NUS comprehensively introduces researchers doing systematic reviews to the search methods for searching systematically from start to finish, including concept modelling, synthesizing a search strategy, to managing search results.

At a glance

  • Institution: NUS
  • Subject: Medicine
  • Level: Introductory
  • Prerequisites: None
  • Language: English
  • Video Transcript: English
  • Associated skills: Environmental Science, Social Sciences, Policy Studies, Health Sciences, Research

What you'll learn

The focus of this course is on the literature search process. It addresses the commonly faced challenges by offering practical tips and tricks to improve the overall quality and reporting of literature searches.

After completing the course, participants will be able to:

  • Develop a focused research question
  • Select appropriate resources to search for relevant work
  • Construct comprehensive search strategies
  • Document the search process & manage the results

Week 1: Getting Started

Understand the importance of searching in systematic reviews. Know the steps in the systematic review process and the different types of reviews.

Week 2: Develop a focused research question (what to search)

Introduce the structure of a systematic review paper. Assess the feasibility, and scope of the research topic with preliminary searches. Develop a focused research question using question development frameworks such as PICO.

Week 3: Select appropriate resources to search (where to search)

Understand the evidence types available such as subscribed databases, grey literature, hand searches and other unpublished works.

Select information sources relevant to your topic / discipline. Develop a basic search strategy.

Week 4: Construct comprehensive search strategies (how to search)

Formulate comprehensive systematic review searches with step-by-step demonstration videos covering different databases.

Learn practical tips in conducting and replicating systematic review searches.

Week 5: Document the search process & managing the results

Understand where EndNote fits into the systematic review process.

Use EndNote to manage and document the search results from various information sources.

Frequently Asked Questions

I am a social science researcher. Does this course help me to gather evidence for policy making?

Yes, this course will benefit all researchers as we cover a range of information sources across disciplines

If I don’t have access to some of the databases, can I still attend this course?

To fully benefit from the course, you will need to have access to most of the subscription-based databases covered in this course.

You may have access to some or all of these from your institution.

We also cover some of the freely available databases such as PubMed and Cochrane Library.

Can I complete the course and earn a certificate if I don’t have access to some of these resources?

Yes, if you do not have access to some of these databases, you can still complete this course and earn a certificate as the concepts assessed are covered in the teaching materials.

What are the assessments?

This course contains graded (quiz) and ungraded (knowledge check) assessments throughout the course to test your understanding of the topics.

How do I earn a certificate?

Attempt all the graded assessments and achieve 60% passing to earn a certificate.

What is the format of this course?

The course consists of pre-recorded lecture and demonstration videos with accompanying training materials.

Lectures are followed by assessments. The course is self-paced and covers five weeks of content

Ways to take this course

Interested in this course for your business or team.

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  • Knowledge Base

Methodology

  • Systematic Review | Definition, Example, & Guide

Systematic Review | Definition, Example & Guide

Published on June 15, 2022 by Shaun Turney . Revised on November 20, 2023.

A systematic review is a type of review that uses repeatable methods to find, select, and synthesize all available evidence. It answers a clearly formulated research question and explicitly states the methods used to arrive at the answer.

They answered the question “What is the effectiveness of probiotics in reducing eczema symptoms and improving quality of life in patients with eczema?”

In this context, a probiotic is a health product that contains live microorganisms and is taken by mouth. Eczema is a common skin condition that causes red, itchy skin.

Table of contents

What is a systematic review, systematic review vs. meta-analysis, systematic review vs. literature review, systematic review vs. scoping review, when to conduct a systematic review, pros and cons of systematic reviews, step-by-step example of a systematic review, other interesting articles, frequently asked questions about systematic reviews.

A review is an overview of the research that’s already been completed on a topic.

What makes a systematic review different from other types of reviews is that the research methods are designed to reduce bias . The methods are repeatable, and the approach is formal and systematic:

  • Formulate a research question
  • Develop a protocol
  • Search for all relevant studies
  • Apply the selection criteria
  • Extract the data
  • Synthesize the data
  • Write and publish a report

Although multiple sets of guidelines exist, the Cochrane Handbook for Systematic Reviews is among the most widely used. It provides detailed guidelines on how to complete each step of the systematic review process.

Systematic reviews are most commonly used in medical and public health research, but they can also be found in other disciplines.

Systematic reviews typically answer their research question by synthesizing all available evidence and evaluating the quality of the evidence. Synthesizing means bringing together different information to tell a single, cohesive story. The synthesis can be narrative ( qualitative ), quantitative , or both.

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Systematic reviews often quantitatively synthesize the evidence using a meta-analysis . A meta-analysis is a statistical analysis, not a type of review.

A meta-analysis is a technique to synthesize results from multiple studies. It’s a statistical analysis that combines the results of two or more studies, usually to estimate an effect size .

A literature review is a type of review that uses a less systematic and formal approach than a systematic review. Typically, an expert in a topic will qualitatively summarize and evaluate previous work, without using a formal, explicit method.

Although literature reviews are often less time-consuming and can be insightful or helpful, they have a higher risk of bias and are less transparent than systematic reviews.

Similar to a systematic review, a scoping review is a type of review that tries to minimize bias by using transparent and repeatable methods.

However, a scoping review isn’t a type of systematic review. The most important difference is the goal: rather than answering a specific question, a scoping review explores a topic. The researcher tries to identify the main concepts, theories, and evidence, as well as gaps in the current research.

Sometimes scoping reviews are an exploratory preparation step for a systematic review, and sometimes they are a standalone project.

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A systematic review is a good choice of review if you want to answer a question about the effectiveness of an intervention , such as a medical treatment.

To conduct a systematic review, you’ll need the following:

  • A precise question , usually about the effectiveness of an intervention. The question needs to be about a topic that’s previously been studied by multiple researchers. If there’s no previous research, there’s nothing to review.
  • If you’re doing a systematic review on your own (e.g., for a research paper or thesis ), you should take appropriate measures to ensure the validity and reliability of your research.
  • Access to databases and journal archives. Often, your educational institution provides you with access.
  • Time. A professional systematic review is a time-consuming process: it will take the lead author about six months of full-time work. If you’re a student, you should narrow the scope of your systematic review and stick to a tight schedule.
  • Bibliographic, word-processing, spreadsheet, and statistical software . For example, you could use EndNote, Microsoft Word, Excel, and SPSS.

A systematic review has many pros .

  • They minimize research bias by considering all available evidence and evaluating each study for bias.
  • Their methods are transparent , so they can be scrutinized by others.
  • They’re thorough : they summarize all available evidence.
  • They can be replicated and updated by others.

Systematic reviews also have a few cons .

  • They’re time-consuming .
  • They’re narrow in scope : they only answer the precise research question.

The 7 steps for conducting a systematic review are explained with an example.

Step 1: Formulate a research question

Formulating the research question is probably the most important step of a systematic review. A clear research question will:

  • Allow you to more effectively communicate your research to other researchers and practitioners
  • Guide your decisions as you plan and conduct your systematic review

A good research question for a systematic review has four components, which you can remember with the acronym PICO :

  • Population(s) or problem(s)
  • Intervention(s)
  • Comparison(s)

You can rearrange these four components to write your research question:

  • What is the effectiveness of I versus C for O in P ?

Sometimes, you may want to include a fifth component, the type of study design . In this case, the acronym is PICOT .

  • Type of study design(s)
  • The population of patients with eczema
  • The intervention of probiotics
  • In comparison to no treatment, placebo , or non-probiotic treatment
  • The outcome of changes in participant-, parent-, and doctor-rated symptoms of eczema and quality of life
  • Randomized control trials, a type of study design

Their research question was:

  • What is the effectiveness of probiotics versus no treatment, a placebo, or a non-probiotic treatment for reducing eczema symptoms and improving quality of life in patients with eczema?

Step 2: Develop a protocol

A protocol is a document that contains your research plan for the systematic review. This is an important step because having a plan allows you to work more efficiently and reduces bias.

Your protocol should include the following components:

  • Background information : Provide the context of the research question, including why it’s important.
  • Research objective (s) : Rephrase your research question as an objective.
  • Selection criteria: State how you’ll decide which studies to include or exclude from your review.
  • Search strategy: Discuss your plan for finding studies.
  • Analysis: Explain what information you’ll collect from the studies and how you’ll synthesize the data.

If you’re a professional seeking to publish your review, it’s a good idea to bring together an advisory committee . This is a group of about six people who have experience in the topic you’re researching. They can help you make decisions about your protocol.

It’s highly recommended to register your protocol. Registering your protocol means submitting it to a database such as PROSPERO or ClinicalTrials.gov .

Step 3: Search for all relevant studies

Searching for relevant studies is the most time-consuming step of a systematic review.

To reduce bias, it’s important to search for relevant studies very thoroughly. Your strategy will depend on your field and your research question, but sources generally fall into these four categories:

  • Databases: Search multiple databases of peer-reviewed literature, such as PubMed or Scopus . Think carefully about how to phrase your search terms and include multiple synonyms of each word. Use Boolean operators if relevant.
  • Handsearching: In addition to searching the primary sources using databases, you’ll also need to search manually. One strategy is to scan relevant journals or conference proceedings. Another strategy is to scan the reference lists of relevant studies.
  • Gray literature: Gray literature includes documents produced by governments, universities, and other institutions that aren’t published by traditional publishers. Graduate student theses are an important type of gray literature, which you can search using the Networked Digital Library of Theses and Dissertations (NDLTD) . In medicine, clinical trial registries are another important type of gray literature.
  • Experts: Contact experts in the field to ask if they have unpublished studies that should be included in your review.

At this stage of your review, you won’t read the articles yet. Simply save any potentially relevant citations using bibliographic software, such as Scribbr’s APA or MLA Generator .

  • Databases: EMBASE, PsycINFO, AMED, LILACS, and ISI Web of Science
  • Handsearch: Conference proceedings and reference lists of articles
  • Gray literature: The Cochrane Library, the metaRegister of Controlled Trials, and the Ongoing Skin Trials Register
  • Experts: Authors of unpublished registered trials, pharmaceutical companies, and manufacturers of probiotics

Step 4: Apply the selection criteria

Applying the selection criteria is a three-person job. Two of you will independently read the studies and decide which to include in your review based on the selection criteria you established in your protocol . The third person’s job is to break any ties.

To increase inter-rater reliability , ensure that everyone thoroughly understands the selection criteria before you begin.

If you’re writing a systematic review as a student for an assignment, you might not have a team. In this case, you’ll have to apply the selection criteria on your own; you can mention this as a limitation in your paper’s discussion.

You should apply the selection criteria in two phases:

  • Based on the titles and abstracts : Decide whether each article potentially meets the selection criteria based on the information provided in the abstracts.
  • Based on the full texts: Download the articles that weren’t excluded during the first phase. If an article isn’t available online or through your library, you may need to contact the authors to ask for a copy. Read the articles and decide which articles meet the selection criteria.

It’s very important to keep a meticulous record of why you included or excluded each article. When the selection process is complete, you can summarize what you did using a PRISMA flow diagram .

Next, Boyle and colleagues found the full texts for each of the remaining studies. Boyle and Tang read through the articles to decide if any more studies needed to be excluded based on the selection criteria.

When Boyle and Tang disagreed about whether a study should be excluded, they discussed it with Varigos until the three researchers came to an agreement.

Step 5: Extract the data

Extracting the data means collecting information from the selected studies in a systematic way. There are two types of information you need to collect from each study:

  • Information about the study’s methods and results . The exact information will depend on your research question, but it might include the year, study design , sample size, context, research findings , and conclusions. If any data are missing, you’ll need to contact the study’s authors.
  • Your judgment of the quality of the evidence, including risk of bias .

You should collect this information using forms. You can find sample forms in The Registry of Methods and Tools for Evidence-Informed Decision Making and the Grading of Recommendations, Assessment, Development and Evaluations Working Group .

Extracting the data is also a three-person job. Two people should do this step independently, and the third person will resolve any disagreements.

They also collected data about possible sources of bias, such as how the study participants were randomized into the control and treatment groups.

Step 6: Synthesize the data

Synthesizing the data means bringing together the information you collected into a single, cohesive story. There are two main approaches to synthesizing the data:

  • Narrative ( qualitative ): Summarize the information in words. You’ll need to discuss the studies and assess their overall quality.
  • Quantitative : Use statistical methods to summarize and compare data from different studies. The most common quantitative approach is a meta-analysis , which allows you to combine results from multiple studies into a summary result.

Generally, you should use both approaches together whenever possible. If you don’t have enough data, or the data from different studies aren’t comparable, then you can take just a narrative approach. However, you should justify why a quantitative approach wasn’t possible.

Boyle and colleagues also divided the studies into subgroups, such as studies about babies, children, and adults, and analyzed the effect sizes within each group.

Step 7: Write and publish a report

The purpose of writing a systematic review article is to share the answer to your research question and explain how you arrived at this answer.

Your article should include the following sections:

  • Abstract : A summary of the review
  • Introduction : Including the rationale and objectives
  • Methods : Including the selection criteria, search method, data extraction method, and synthesis method
  • Results : Including results of the search and selection process, study characteristics, risk of bias in the studies, and synthesis results
  • Discussion : Including interpretation of the results and limitations of the review
  • Conclusion : The answer to your research question and implications for practice, policy, or research

To verify that your report includes everything it needs, you can use the PRISMA checklist .

Once your report is written, you can publish it in a systematic review database, such as the Cochrane Database of Systematic Reviews , and/or in a peer-reviewed journal.

In their report, Boyle and colleagues concluded that probiotics cannot be recommended for reducing eczema symptoms or improving quality of life in patients with eczema. Note Generative AI tools like ChatGPT can be useful at various stages of the writing and research process and can help you to write your systematic review. However, we strongly advise against trying to pass AI-generated text off as your own work.

If you want to know more about statistics , methodology , or research bias , make sure to check out some of our other articles with explanations and examples.

  • Student’s  t -distribution
  • Normal distribution
  • Null and Alternative Hypotheses
  • Chi square tests
  • Confidence interval
  • Quartiles & Quantiles
  • Cluster sampling
  • Stratified sampling
  • Data cleansing
  • Reproducibility vs Replicability
  • Peer review
  • Prospective cohort study

Research bias

  • Implicit bias
  • Cognitive bias
  • Placebo effect
  • Hawthorne effect
  • Hindsight bias
  • Affect heuristic
  • Social desirability bias

A literature review is a survey of scholarly sources (such as books, journal articles, and theses) related to a specific topic or research question .

It is often written as part of a thesis, dissertation , or research paper , in order to situate your work in relation to existing knowledge.

A literature review is a survey of credible sources on a topic, often used in dissertations , theses, and research papers . Literature reviews give an overview of knowledge on a subject, helping you identify relevant theories and methods, as well as gaps in existing research. Literature reviews are set up similarly to other  academic texts , with an introduction , a main body, and a conclusion .

An  annotated bibliography is a list of  source references that has a short description (called an annotation ) for each of the sources. It is often assigned as part of the research process for a  paper .  

A systematic review is secondary research because it uses existing research. You don’t collect new data yourself.

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Systematic Reviews

Who is this guide for and what can be found in it, what are systematic reviews, how do systematic reviews differ from narrative literature reviews.

  • Types of Systematic Reviews
  • Reading Systematic Reviews
  • Resources for Conducting Systematic Reviews
  • Getting Help with Systematic Reviews from the Library
  • History of Systematic Reviews
  • Acknowledgements

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This guide aims to support all OHSU members' systematic review education and activities, orienting OHSU members who are new to systematic reviews and facilitating the quality, rigor, and reproducibility of systematic reviews produced by OHSU members.

In it you will find:

  • A definition of what systematic reviews are, how they compare to other evidence, and how they differ from narrative literature reviews
  • Descriptions of the different types of systematic reviews , with links to resources on methods, protocols, reporting, additional information, and selecting the right type of systematic review for your research question
  • Guidance on how to read and evaluate systematic reviews for strength, quality, and potential for bias
  • A high-level overview of how systematic reviews are conducted , including team size and roles, standards, and processes
  • Links to resources and tools for conducting systematic reviews
  • Information about how to get assistance with conducting a systematic review from the OHSU Library
  • A history of systematic reviews to provide contextual understanding of how they have developed over time
"A systematic review is a summary of the medical literature that uses explicit and reproducible methods to systematically search, critically appraise, and synthesize on a specific issue. It synthesizes the results of multiple primary studies related to each other by using strategies that reduce biases and random errors."

Gopalakrishnan S, Ganeshkumar P. Systematic Reviews and Meta-analysis: Understanding the Best Evidence in Primary Healthcare . J Family Med Prim Care . 2013;2(1):9-14. doi:10.4103/2249-4863.109934

Systematic Reviews are a vital resource used in the pursuit of Evidence-Based Practice (EBP):

  • These studies can be found near the top of the Evidence Pyramid , which ranks sources of information and study designs by the level of evidence contained within them
  • This ranking is based on the level of scientific rigor employed in their methods and the quality and reliability of the evidence contained within these sources
  • A higher ranking means that we can be more confident that their conclusions are accurate and have taken measures to limit bias

Research design and evidence , by CFCF , CC BY-SA 4.0 , via Wikimedia Commons

Things to know about systematic reviews:

  • Systematic reviews are a type of research study
  • Systematic reviews aim to provide a comprehensive and unbiased summary of the existing evidence on a particular research question
  • There are many types of systematic reviews , each designed to address a specific type of research purpose and with their own strengths and weaknesses
  • The choice of what type of review to produce typically will depend on the nature of the research question and the resources that are available on the topic

The practice of producing systematic reviews is sometimes referred to by other names such as:

  • Evidence Synthesis
  • Knowledge Synthesis
  • Research Synthesis

This guide tries to stick with the term "Systematic Reviews" unless a specific type of systematic review is being discussed.

While all reviews combat information overload in the health sciences by summarizing the literature on a topic, different types of reviews have different approaches. The term systematic review is often conflated with narrative literature reviews , which can lead to confusion and misunderstandings when seeking help with conducting them. This table helps clarify the differences.

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Evidence Syntheses and Systematic Reviews: Overview

  • Choosing a Review

Analyze and Report

What is evidence synthesis.

Evidence Synthesis: general term used to refer to any method of identifying, selecting, and combining results from multiple studies. There are several types of reviews which fall under this term; the main ones are in the table below: 

Types of Reviews

General steps for conducting systematic reviews.

The number of steps for conducting Evidence Synthesis varies a little, depending on the source that one consults. However, the following steps are generally accepted in how Systematic Reviews are done:

  • Identify a gap in the literature and form a well-developed and answerable research question which will form the basis of your search
  • Select a framework that will help guide the type of study you’re undertaking
  • Different guidelines are used for documenting and reporting the protocols of your systematic review before the review is conducted. The protocol is created following whatever guideline you select.
  • Select Databases and Grey Literature Sources
  • For steps 3 and 4, it is advisable to consult a librarian before embarking on this phase of the review process. They can recommend databases and other sources to use and even help design complex searches.
  • A protocol is a detailed plan for the project, and after it is written, it should be registered with an appropriate registry.
  • Search Databases and Other Sources
  • Not all databases use the same search syntax, so when searching multiple databases, use search syntaxes that would work in individual databases.
  • Use a citation management tool to help store and organize your citations during the review process; great help when de-duplicating your citation results
  • Inclusion and exclusion criteria already developed help you remove articles that are not relevant to your topic. 
  • Assess the quality of your findings to eliminate bias in either the design of the study or in the results/conclusions (generally not done outside of Systematic Reviews).

Extract and Synthesize

  • Extract the data from what's left of the studies that have been analyzed
  • Extraction tools are used to get data from individual studies that will be analyzed or summarized. 
  • Synthesize the main findings of your research

Report Findings

Report the results using a statistical approach or in a narrative form.

Need More Help?

Librarians can:

  • Provide guidance on which methodology best suits your goals
  • Recommend databases and other information sources for searching
  • Design and implement comprehensive and reproducible database-specific search strategies 
  • Recommend software for article screening
  • Assist with the use of citation management
  • Offer best practices on documentation of searches

Related Guides

  • Literature Reviews
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  • Project Management

Steps of a Systematic Review - Video

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  • Last Updated: Feb 16, 2024 5:40 PM
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Literature Reviews

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What is a literature review?

Why conduct a literature review, stages of a literature review, lit reviews: an overview (video), check out these books.

  • Types of reviews
  • 1. Define your research question
  • 2. Plan your search
  • 3. Search the literature
  • 4. Organize your results
  • 5. Synthesize your findings
  • 6. Write the review
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Definition: A literature review is a systematic examination and synthesis of existing scholarly research on a specific topic or subject.

Purpose: It serves to provide a comprehensive overview of the current state of knowledge within a particular field.

Analysis: Involves critically evaluating and summarizing key findings, methodologies, and debates found in academic literature.

Identifying Gaps: Aims to pinpoint areas where there is a lack of research or unresolved questions, highlighting opportunities for further investigation.

Contextualization: Enables researchers to understand how their work fits into the broader academic conversation and contributes to the existing body of knowledge.

systematic literature review course

tl;dr  A literature review critically examines and synthesizes existing scholarly research and publications on a specific topic to provide a comprehensive understanding of the current state of knowledge in the field.

What is a literature review NOT?

❌ An annotated bibliography

❌ Original research

❌ A summary

❌ Something to be conducted at the end of your research

❌ An opinion piece

❌ A chronological compilation of studies

The reason for conducting a literature review is to:

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  • Published: 15 February 2024

Psychotic illness in people with Prader–Willi syndrome: a systematic review of clinical presentation, course and phenomenology

  • Lucie C. S. Aman   ORCID: orcid.org/0000-0002-5252-8873 1 ,
  • Suzannah D. Lester 1 ,
  • Anthony J. Holland 1 &
  • Paul C. Fletcher 1 , 2 , 3  

Orphanet Journal of Rare Diseases volume  19 , Article number:  69 ( 2024 ) Cite this article

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Prader–Willi syndrome (PWS) is a rare and complex neurodevelopmental disorder resulting from absent paternal expression of maternally imprinted genes at chromosomal locus 15q11-13. This absence of expression occurs as a consequence of a deletion on the chromosome 15 of paternal origin ( ca. 70%), a chromosome 15 maternal uniparental disomy (mUPD; ca. 25%), or an imprinting centre defect (IC; ca . 1–3%). At birth, individuals with PWS are severely hypotonic and fail to thrive. Hyperphagia and characteristic physical and neuropsychiatric phenotypes become apparent during childhood. The risk for the development of a co-morbid psychotic illness increases during the teenage years, specifically in those with PWS due to the presence of an mUPD. The primary aim of this literature review is to inform clinical practice. To achieve this, we have undertaken a systematic analysis of the clinical research literature on prevalence, presentation, course, characteristics, diagnosis and treatment of psychotic illness in people with PWS. The secondary aim is to identify clinical aspects of psychotic illness in PWS in need of further investigation.

Methods and findings

A systematic literature review on psychosis in PWS was conducted on the databases Web of Knowledge, PubMed and Scopus, using the terms “((Prader–Willi syndrome) OR (Prader Willi Syndrome)) AND ((psychosis) OR (psychotic illness))”. All articles written in English and reporting original human research were reviewed. In all but three of the 16 cohort studies in which the genetic types were known, the authors reported higher rates of psychosis in people with PWS resulting from an mUPD, compared to those with the deletion subtype of PWS. When psychosis was present the presentation was psychosis similar regardless of genetic type and was usually characterised by an acute onset of hallucinations and delusions accompanied by confusion, anxiety and motor symptoms.

Conclusions

The onset of confusion, an affective cyclical pattern with the presence of abnormal mental beliefs and experiences, usually of rapid onset is suggestive of the development of psychotic illness. Phenomenologically, this psychosis in people with PWS is atypical in comparison to schizophrenia and bipolar disorder in the general population. The relationship to psychosis in the general population and the optimum treatments remain uncertain.

Prader–Willi syndrome and the association with psychotic illness

Prader–Willi syndrome (PWS) is a rare genetically determined neurodevelopmental disorder with a birth incidence of around 1:24,000 and a population prevalence of 1:45,000 to 1:52,000 [ 1 ]. As we describe below, high rates of severe psychotic illness, particularly in those with the rarer genetic form of PWS, have been reported and people with PWS may present to Accident and Emergency or mental health services serious ill and in crisis. The aim of this systematic clinical review is to evaluate existing clinical evidence so as to inform the identification, assessment and treatment of psychotic illness when it presents in people with this rare syndrome. This clinical review complements an earlier review that focussed on underlying mechanisms [ 2 ].

PWS results from the absence or failure of expression of alleles of paternal origin of maternally imprinted genes located at the chromosomal locus 15q11-13. This arises as a consequence of one the following: 15q11-13 de novo deletion on the chromosome 15 of paternal origin (del; ca. 70%), chromosome 15 maternal uniparental disomy (mUPD; ca. 25%), an imprinting centre defect (ICD; ca. 3–5%), or an unbalanced translocation of chromosome 15 (< 5%) (see Fig.  1 ).

figure 1

Adapted from the foundation for Prader–Willi research (FPWR) website

Genetic subtypes of Prader–Willi syndrome.

The main features of the syndrome at birth are extreme hypotonia and failure to thrive, followed by the development of hyperphagia in early childhood, which if not managed through controlling access to food, results in severe obesity and high rate of morbidity and mortality [ 3 ]. In addition, there is developmental delay associated with intellectual and social impairments, and short stature and impaired sexual development as a result of relative growth and sex hormone deficiencies, respectively. Specific neuropsychiatric symptomatology includes an increased propensity to severe emotional outbursts, anxiety, repetitive and ritualistic behavior, and severe skin picking [ 4 ]. For more detailed information about the manifestations of PWS, see [ 5 , 6 ].

Whilst people with PWS, regardless of the genetic subtype, share a similar profile of non-psychotic psychopathology and problem behaviors, in the case of psychotic illness significantly higher rates are observedin those those with PWS due to (mUPD) compared with those with PWS due to paternal deletion. Given the rarity of the syndrome, and particularly of the rarity of people with the mUPD genetic type, few clinicians have experience in the recognition, diagnosis, and treatment of psychotic illness in this population. In the context of the broader complex neuropsychiatric phenotype characteristic of PWS, the challenge is to ensure that psychosis is diagnosed accurately and in a timely manner and that effective treatment and appropriate support is then provided.

This systematic clinical review focuses specifically on psychotic illness in people with PWS and not on the broader PWS neuropsychiatric phenotype. The search was conducted on the databases Web of Knowledge, Pubmed and Scopus, using the terms “((Prader–Willi syndrome) OR (Prader Willi Syndrome)) AND ((psychosis) OR (psychotic illness))”. Automatic tools were used to reject articles not written in English, non-human research, and all reports that were not articles, case reports or reviews. All those articles selected were reviewed. Using these criteria, 169 original articles, published between 1987 and February 2023 were identified. Two additional articles, identified from article reference lists, were also included. The selection process is described in Fig.  2 using a PRISMA flow diagram [ 7 ]. A total of 73 articles were included for detailed analysis. Eighteen articles described cohort studies, and the overall number of individuals with PWS reported by these cohorts studies was 1556. Thirty-three articles were case reports, describing a total of 89 cases. In 58 of the 89 case reports, the PWS genetic subtype was reported (see Table  2 ), and in the other 31, genetic information was not available (see Table  3 ).

figure 2

PRISMA flow diagram reporting the article identification process for systematic literature review of psychosis in Prader–Willi syndrome (PWS)

Literature searches were carried out between May 2019 and October 2023 by the first author.

The findings reported in the tables below are predominantly summaries of descriptive information about psychotic illness in this population, taken from both case reports and cohort studies. Using the more detailed and individual data from the 58 case studies in which genetic information was available, we also compared the presentation, course and phenomenology of psychotic illness in those who had PWS due to a mUPD and those who had a paternal chromosome 15 deletions and who also had had a psychotic illness. Because of similar genetic expression patterns, we group the very rare patients with imprinting centre defects with those with mUPD, and those with rare chromosomal translocations with patients with a deletion.

Psychotic illness in PWS: an historical background

Prader et al. [ 8 ] first described what later became known as Prader–Willi syndrome in 1956. The occurrence of psychosis in someone with PWS was first reported 10 years later [ 9 ]. While several papers [ 10 , 11 , 12 , 13 ] noted a range of symptoms suggesting that the onset of psychotic illness was a specific feature of PWS, there was little reported in the literature on psychotic symptoms in people with PWS for two decades after these earlier reports. The symptoms of psychotic illness in PWS initially described in the above papers include references to hallucinations [ 14 , 15 ] and paranoid delusion, agitation, and catatonia [ 10 , 11 , 12 , 13 ] (see Table  3 ). These papers were predominantly in the form of case studies and the findings could not be reliably generalized to the PWS population. However, these early cohort studies that focused particular attention on the presence of psychotic illness in PWS [ 11 ], along with two early cohort studies [ 16 , 17 ] demonstrated clear evidence that specific phenomenology characteristic of psychotic illness was associated with PWS.

In the Beardsmore et al. [ 16 ] study, high rates of psychotic symptoms were reported in people with PWS compared to a control group of people with learning disabilities. Unfortunately, as genetic testing was not possible, the authors were unable to ascertain whether psychosis was linked to a specific genetic type of PWS. A later study by Clarke et al. [ 17 ] also confirmed the elevated occurrence of psychotic symptoms in people with PWS, with a prevalence rate of 6.3% in 93 people with a genetic diagnosis of PWS [ 17 ]. Notably, in this study, a high proportion of participants either had the deletion type (n = 34) or the genetic type was unknown (n = 55). Only four participants were confirmed as having an mUPD. The work described above established the link between PWS and psychosis, but the first definitive observation of a differential prevalence rate for psychosis according to genetic type of PWS did not appear until the beginning of this century.

Differential rates of psychosis according to PWS genetic type

The first population-based study to indicate a difference in prevalence rates of psychosis in PWS according to genetic subtype reported only one out of 13 adults with deletion had had evidence of a psychotic illness, compared with five out of eight with mUPD [ 18 ]. Vogels et al. [ 19 ] also investigated psychotic illness in 37 people with PWS aged 13 years or older. Of the 37 individuals, 28 had deletion, and nine had mUPD. Of those nine individuals, six were found to have or have had a psychotic illness (none of the deletion participants were diagnosed with psychotic illness) [ 19 ]. In another study it was reported that of 16 people with PWS referred for neuropsychiatric evaluation because of relapsing psychotic illness, only one individual with PWS had the deletion subtype, while ten of the PWS individuals had mUPD,the genetic subtype of the remaining five was unknown [ 20 ].

In more recent cohort studies, the reported prevalence of psychotic illness between the genetic subtypes of PWS varied. However, in most publications the prevalence of psychosis is higher in the mUPD group compared to the deletion group (see Table  1 and Fig.  3 ). In a cohort study, Soni et al. [ 28 ] estimated the incidences of psychiatric illness of 2.3 per 100 person-years in those with deletions and 6.7 per 100 person-years in those with PWS due to mUPD (see Table  1 ) [ 28 ].

figure 3

Proportion of reported psychotic symptoms in cohort studies according to PWS genetic subtypes

There are three cohort studies that did not find high rates of psychosis in individuals with the mUPD type. In a longitudinal study, 61 children with PWS between seven and 17 years old were assessed for various psychiatric disorders. Thirty-eight out of 61 were re-assessed two years later. During the first assessment, of the 34 individuals with mUPD, they found only two with psychotic disorder [ 29 ]. This discrepancy, when compared to other studies, may be due to the young age of the cohort. Most studies whose findings suggest higher rates of psychosis in mUPD, report an age of onset between 16 and 28 years [ 19 ]. A second study that did not find an association between psychosis and mUPD, was a national informant-based survey conducted in Ireland [ 30 ]. However, this lack of association might have occurred because 80% of individuals with the mUPD subtype were on antipsychotic medication. The third study to not find an association between psychosis and the mUPD type examined the association between growth hormone therapy (GHT) and psychiatric behaviours in PWS. One hundred and seven people with deletion and 57 with mUPD, aged between 8 and 62 years old, were studied to examine differences between genetic types, and differences between GHT and non-GHT participants. The study found no differential rate in psychosis between genetic types. However, limitations to the study’s findings include the fact that information on current and past psychiatric behaviors were collected using parent/guardian assessments, rather than the participants being assessed and diagnosed by mental health professionals. In addition, the participants’ mental health before enrolment in the study, as well as changes during the study, were not reported. No details were given of psychiatric medication use [ 31 ].

Observations from the case reports support the association of psychotic illness with mUPD. As shown in Fig.  4 of the 58 people with PWS and psychosis described in the case reports who had their genetic type listed,, 37 (63.8%) had an mUPD, 19 (32.8%) had a deletion, one had an imprinting centre defect, and one had a translocation. This ratio of mUPD and deletion types is the opposite to what would be expected in relation with the known frequency of each genetic type. However, while the great majority of studies support the observation of an excess of psychotic illness in those with mUPD, it is also clear that people with PWS with a 15q11-13 deletions can develop such an illness, with rates in this population as high as 20%.

figure 4

Rates of genetic subtypes in case reports of psychosis in PWS

Psychopathology

Table 1 summarizes the different psychiatric diagnoses made in the cohorts of people with PWS. In the early clinical research when there was limited agreement as to the main symptoms the classification of the psychotic illness associated with PWS was disputed. In the case studies listed in Tables  2 and 3 it is, however, possible to ascertain the phenomenology of the psychiatric illness in greater detail. The common features include hallucinations, persecutory delusions, heightened anxiety, motor symptoms (catatonia or agitation), confusional states, disturbed sleep (decreased or increased) and mood swings. The clinical picture is usually not consistent with accepted criteria for schizophrenia or specific psychotic disorders, and consequently the diagnosis made has often been atypical psychosis. Other diagnostic labels reported in the literature have, however, including schizophrenia and bipolar disorder with psychotic symptoms, and also cycloid psychosis, florid psychotic states, paranoic-hallucinatory psychosis, depressive psychosis and atypical bipolar disorder (e.g. [ 17 , 20 , 32 , 33 , 34 ]). At present there is no consensus as to the most appropriate diagnostic label for this atypical psychotic disorder. According to Verhoeven [ 35 , 36 ], psychopathology, course, symptomatology and response to pharmacological treatment match with a diagnosis of cycloid psychosis, with the evidence from the clinical evaluation being closer to that of an atypical bipolar disorder [ 34 , 35 , 36 ].

Other authors have classified the psychotic symptoms in PWS more generally. In 1994, Bartolucci and Younger [ 52 ] reported nine cases of neuropsychiatric disorders in people with PWS. They were slightly different in characteristics from known psychotic disorders in the typically developing population with, in general, an earlier onset, cycloid patterns and atypical presentation. They classified these psychiatric symptoms as: (1) trait fluctuation (changes in behavioral and vegetative traits such as refusal of food and drink, food binges, escalation of antisocial behaviour); (2) lethargic-refusal states (refusing the approach of others, having no energy and being in a state of self-neglect); and (3) psychotic states (agitation, insomnia, decrease in hyperphagia, attentional deficits) [ 52 ]. More recently, Thuilleaux et al. [ 53 ] proposed a model to characterise psychopathological features common in adults with PWS. This model includes a profile characterised by ‘a psychotic disorganization of ideas, emotions, and behaviour that is persistently present as a personality trait’. The profile they describe includes loss of links with reality, with or without hallucinations; delusional ideation; strange and disorganized behaviour; and negative symptoms [ 53 ]. It is important to acknowledge that both of these studies published some years apart took a very broad view of psychosis, including in their overall descriptions non-specific symptoms, such as sleep and eating behavior changes. It is difficult to interpret their findings precisely or to relate them specifically to the presence or not of psychosis.

Soni et al. [ 28 ] compared the phenomenology of psychosis in people with PWS who had a mUPD with the cases of psychosis in people with PWS due to a deletion. The question they were seeking to answer was whether a psychotic illness, if it was to develop, was the same in people with PWS regardless of genetic type. She reported more severe affective co-morbidity in those with a psychotic illness and mUPD, but with broad similarities in phenomenological findings and the diagnostic category of affective disorder, except for the duration of the first psychotic episode. Analysis of the 56 case reports included in this review, also found similar levels of positive symptoms, such as delusions and hallucinations, but in contrast to Soni et al. [ 28 ] there were higher levels of anxiety in those with a paternal deletion, and more confusion and mood swings in those with mUPD (see Fig.  5 ).

figure 5

Percentage of psychiatric symptoms according to genetic subtype reported in case study reports

Age of onset

The age of onset of psychotic illness in people with PWS is highly variable. In the reviewed articles, where it was specified, we found an age of onset ranging between eight years [ 29 ] and 40 years of age [ 28 ]. The age of high risk is generally during the teenage years or early adulthood, and tends, on average, to be earlier than the onset of psychotic illnesses in the general population. (See Table  1 for mean age of onset in cohort studies.). The mean age of onset differs between studies largely because of the relatively small size of most of the samples and differences in the way in which age of onset was established.

Type of onset

Most case studies report an acute onset [ 17 , 20 ], whereas longitudinal studies report various types of onsets. Vogels et al. [ 19 ] in their study including 59 people with PWS followed up for a minimum of 10 years, described six people with psychotic symptoms, all with acute onset. However, Soni et al. [ 28 ] found in their cohort study only a slightly increased likelihood of acute rather than insidious onset.

The duration of first episodes of psychosis varied. According to Soni et al. [ 28 ] those with mUPD experienced a shorter duration of a first major psychotic episode compared to first episodes of psychosis in individuals with deletion genetic type, with a good recovery between episodes and overall, a good response to treatments. In a follow-up study, Larson et al. [ 54 ] identified 20 people with PWS due to mUPD who had had a psychotic illness and had been seen as part of the Soni et al. [ 28 ] study [ 28 , 54 ]. Two or more years later, two of the participants had a relapse of their psychotic illness. The others remained mentally well but on psychiatric medications (see Table  1 for more details).

Risk and protective factors

Some case and cohort studies have reported details of the circumstances in which the first episode, and sometimes the subsequent episodes, occurred. When reported, the first episodes often indicated the presence of a potential stressor, such as a life event, a physical illness or a change in routine and/or environment (e.g. severe illness or death of a relative, change of school or diet, holidays) [ 17 , 38 , 44 ]. It has been proposed that developmental brain changes associated with adolescence and an underlying genetic predisposition to affective disorder and psychosis associated with PWS results in an increasing vulnerability to psychosis with age. The illness first becomes apparent in adolescence or early adult life as a consequence of some additional environmental stressor (see [ 55 ]). What is uncertain is whether treatments, such as growth hormone and various psychiatric medications, when administered from childhood reduce the risk of the subsequent development of psychotic symptoms. Interestingly, Background genetics may also be important particularly in those with a deletion. Soni et al. [ 28 ] reported that 50% of the deletion group with a history of psychosis in her cohort also had a history of an affective disorder in a first-degree relative, and in all cases it was in the mother. In some cases the affective disorder had been present before the child with PWS was born suggesting that maternal depression could not in these cases be explained by the emotional impact of having a child with PWS. This led to the authors proposing a two hit model for psychotic illness: the first is a predisposition to affective instability common to PWS regardless of the genetic type. The second hit is associated with the specific psychopathological effects of having an mUPD or, in the case of those with a deletion, a genetic loading for affective disorder on the maternal side.

Soni et al. [ 56 ] noticed that life events preceding a first episode of psychosis were often associated with physical illness in addition to changes in routine. The hypothesis that an immune response might trigger the onset of a psychotic illness is supported by reports of some individuals with PWS developing psychosis alongside physical symptoms. Vogels et al. [ 19 ] reported that all six patients with PWS and psychotic symptoms described gastro-intestinal problems in addition to other physical symptoms, such as fever and sore throat. Similarly, Takhar and Malla [ 50 ] described a person with PWS with multiple gastro-intestinal problems, urinary incontinence, urinary infection and hepatitis. Some limited support for an immunological component comes from a recent study of 20 participants with PWS. The authors reported that higher levels of IL-1β in participants with PWS were associated with more severe symptoms of withdrawal/depression and thought problems. These symptoms are associated with higher risk of developing psychotic and bipolar disorders [ 57 ].

Given the reported presence of confusion and the possibility of a physical illness triggering an immune response, the possibility of an auto-antibody response to specific neural tissue as the cause of the symptoms needs investigation. However, why this would cause the psychosis to predominately affect those with PWS due to mUPD is unclear. Alternatively, the urinary and gastro-intestinal problems might be explained by an autonomic nervous system dysfunction. All of the six people with PWS who developed psychosis in the Vogels et al. [ 44 ] study showed gastro-intestinal symptoms, and two had enuresis. Bhate et al. [ 46 ] reported psychotic symptoms and enuresis (with no obvious cause) in a 36-year-old women with PWS. Autonomic system dysfunction is associated with an increased risk of psychosis in the general population; and heart rate variability is known to be reduced in people with schizophrenia and individuals at high risk of psychosis [ 58 ].

Modifications in the dosage of medications whose actions are on the brain have also been reported to precede the onset of psychosis. One case of rapid-cycling bipolar illness and one case of psychotic illness were thought to have been triggered by the sudden withdrawing of the appetite suppressants, fenfluramine and sibutramine. Fenfluramine is known to increase serotonin availability in the brain and sibutramine inhibits re-uptake of serotonin, noradrenaline and dopamine [ 56 ]. Similarly, Herguner et al. described a 13-year-old girl with PWS whose psychosis had apparently been triggered by the administration of the selective serotonin reuptake inhibitor, fluoxetine [ 43 ]. Frances et al. [ 59 ] also indicate that antidepressant drugs may have precipitated mania or rapid-cycling bipolar disorder. A 2018 neuroimaging study found that participants in the mUPD group had lower brain-stem serotonin receptor availability compared with the deletion group. This might signify that those with mUPD have a lower synaptic serotonin concentration compared with those with deletion, and might be an indicator as to why there is the greater prevalence of affective psychotic illness in this specific population [ 60 ].

Whether changes in sex hormone levels with age or the atypical sex hormone environment consequent upon impaired hypothalamic function associated with PWS is relevant to the onset of psychosis is unknown. However, Bhate et al. [ 46 ] described a 36-year-old woman with PWS who developed psychosis a few months after the onset of secondary amenorrhea and one patient, described by Clarke et al. [ 17 ], developed psychotic symptoms after a second injection of testosterone. Soni et al. [ 28 ] observed that some features of psychosis in PWS are similar to those that develop during post-partum psychosis (bipolarity and confusional states), an illness that occurs at a time of hormonal change.

It has been reported that growth hormone could have a protective action, limiting the risk of developing psychosis by improving cell-to-cell communication in the brain [ 61 ]. However, Singh et al. [ 37 ] reported that seven out of 11 cases of people with PWS who had been treated with growth hormone also developed a co-morbid psychotic illness. Given that a generation of children treated with growth hormone during early childhood are now reaching the age of risk of developing psychosis, further cohort studies are required to investigate the effects of growth hormone therapy on the risk of psychopathology in people with PWS [ 37 ].

There have been no controlled trials that have specifically investigated the outcomes of treatments for psychotic illness when using established psychiatric medications in people with PWS. The quality of the evidence on treatment is therefore at the level of clinical opinion. The general approach in clinical practice has been to use atypical neuroleptics, anti-depressants and mood stabilising medications, as is standard in the general population. When the names of medications were included in the paper, they have been listed in Tables  2 and 3 . However, it is difficult to draw any conclusion regarding treatment because information is rarely given in sufficient detail. Moreover, very little data is available on long-term mental state stability following specific treatments. We found only three cohort follow-up studies in this literature rsearch. Larson et al. [ 54 ] reported that of the13 out of 22 people who had been psychotic, the majority had done well but only two had been taken off their anti-psychotic medication after two years. Soni et al. [ 56 ] followed up the participants in their cohort 2.5 years after the original study. Individuals with mUPD were more likely to experience recurrent episodes, and usually had been prescribed a greater number of psychiatric medications before finding one that elicited a satisfactory response. In this study, the authors also state that once the right medication is found, individuals with PWS and psychotic illness had a sustained positive response to antipsychotic and antidepressant drugs in general, and that patients treated with these medications are less likely to develop an episode of illness in the future [ 56 ].

Psychopharmacology

Based on the case reports it seems that risperidone, an atypical anti-psychotic, is often used with a satisfactory outcome. This is confirmed by a study published by Bonnot et al. [ 62 ]. However, a clinical trial on pharmacological treatment of psychosis in PWS is needed. The risks and benefits of using antidepressant medication in people with PWS experiencing or at risk of psychosis is still uncertain. Soni et al. [ 56 ] reported that fluoxetine and other SSRIs, were commonly prescribed. However, Frances et al. [ 59 ] indicated that antidepressant drugs may precipitate mania or rapid-cycling bipolar disorder. A case report published in 2007 also described a 13 year-old girl with PWS who had psychotic symptoms triggered by the administration of fluoxetine [ 43 ]. Mood stabilizing medications, such as lithium, have also been used in combination with anti-psychotic drugs, therefore making it difficult to assess the effectiveness or each. Many studies described patients taking mood stabilising medications, but very few studies reported if the medication had been started before, with or after anti-psychotic medication, and the outcomes are rarely reported. Verhoeven et al. [ 35 ] described positive effects of mood stabilizing medication on the course of illness and preventing relapses, but this was not found by Bartolucci and Younger [ 52 ] and Soni et al. [ 56 ].

The rarity of PWS and particularly of those with the mUPD genetic subtypes makes systematic studies of adequate size problematic and the evidence limited. In addition, most psychiatrists are unlikely to see many affected people, if any, and therefore their experience will be limited when it comes to assessment and treatment. The aim of this review is to try to remedy this by bringing the available evidence together to inform clinical practice.

Given the nature of the existing literature, we carried out a primarily descriptive analysis based on information gathered from case reports and cohort studies. While some cohort studies allowed the differential risk for psychotic illness, depending on the genetic type, to be analysed, in many instances they did not provide specific descriptions of psychotic symptoms. Furthermore, in some earlier studies, genetic information was either not present or incomplete.

The evidence reviewed in this paper from several sources indicates a high risk of psychotic illness among those with the mUPD subtype. This risk is observed to increase during the teenage years and early adulthood and is seen to plateau in adult life. In cohort studies, the rates of psychosis in those with mUPD are significantly greater than for those with the deletion subtype, with prevalence rates of psychosis in those with mUPD as high as 60%. However, it is important to note that when case and cohort studies are combined, the evidence suggests that psychotic illness in people with PWS due to a mUPD is not inevitable.

The precise diagnostic status of the psychotic illnesses remains unclear. The studies suggest a strong affective component with mood instability and hypomanic and depressive phases and the presence of delusions and/or hallucinations. Strikingly, confusion has been described as a feature, although it is uncertain whether that includes disorientation in time and place. What is described as “confusion” may be similar to what might be best described as perplexity. Motor abnormalities have also been reported. This combination is similar to the profile of symptoms for the diagnosis of cycloid psychosis [ 63 ]. Their overview of cycloid psychosis provides a useful historical background summarizing the original work of Leonhard, who argued against Kraepelin’s schizophrenia and manic-depressive illness divide and making the case that cycloid psychoses (in plural) as a third group of psychotic illnesses. This third group has beendescribed as a delusional affective psychosis or ‘anxiety-elation’ psychosis and conceptualised according to Leonhard as a combination of symptomatology across bipolar axial syndromes: anxiety-happiness, excitation-inhibition-confusion, and hypermobility-hypomobility. Later work introduced operational criteria [ 64 ] with the main defining features including acute onset, remitting course, symptom polymorphism, and benign outcome in the long term [ 63 ]. In the DSM and ICD systems, cycloid psychosis has not been included. From a nosological perspective, the clinical picture of psychosis affecting people with PWS is certainly close to that of cycloid psychosis and appears to be closer to an affective disorder than to schizophrenia.

The presence of psychosis should therefore be considered where there is a clear and sudden deterioration in behavior and mental state, perhaps preceded by a physical illness or a stressful life event.

Importantly, the onset, mental state characteristics and persistence over time distinguish it from other manifestations of the wider PWS neuropsychiatric phenotype, such as severe behavoral/emotional outbursts. Such outbursts are common among people with PWS and are often present since childhood and triggered by change or frustration. These are not by themselves indicative of psychotic illness (see [ 6 ] for a detailed description of the neuropsychiatric phenotype).

In the absence of any formal treatment trial for psychotic illness in people with PWS, the assumption has been in the literature that standard treatments for psychosis and/or affective disorders are appropriate. One outcome study suggests a good prognosis with such an approach but with the probable need for continued psychiatric medication [ 54 ]. As described in this review, the use of multiple medications, given at different times in the course of the illness and at different doses, limits the conclusions that can be drawn from the papers reviewed. The evidence summarized in this review indicates that the onset is acute and can be severe, and therefore initial treatment, once a diagnosis has been established, will almost certainly be the use of antipsychotic or sedative medication to reduce agitation and to treat any mood disorder and abnormal mental beliefs or experiences. Clinical practice, when treating mental illness in people with a neurodevelopmental disability, is to start at a lower-than-normal dose and increase slowly, depending on clinical response. For people with PWS, an added problem is the effect of psychiatric medication on appetite and weight and for this reason olanzapine is best avoided. Additional co-morbidities that may be weight-related, such as sleep apnea, are also of concern. However, the problem remains that the level of evidence is limited. Multi-centred longitudinal studies, which are able to recruit sufficient numbers of people with PWS of both genetic types reaching the age at risk for psychotic illness, are needed. Such a clinical study could focus on the identification of early clinical and other risk markers for developing psychosis and identifying life events and antecedents that precede psychosis to inform our understanding of aetiology.

Future clinical research

A multi-site study might also identify sufficient numbers of people with mUPD who are mentally stable or have passed the age most at risk of psychosis to provide clues as to potentially individual or environmental protective factors, both at the level of the individual and the environment. The question remains as to whether the aetiology and underlying mechanisms that result in the development of a psychotic illness are the same in those with a deletion compared to those with mUPD. Clinically, the psychotic illness seems similar but not identical, with more affective symptoms in those who have a mUPD. In addition, Soni et al. [ 28 ] suggests maternal history of affective disorder as having a potential role in the development of psychosis in those with a deletion who develop psychotic symptoms, suggesting further investigation of maternal affective disorder is warranted. Furthermore, this observation of a differential risk for psychotic illness, dependent on genetic type, points to potential novel genetic mechanisms that may inform our understanding of psychotic illness in the general population. Our work on these possible mechanisms has been published in [ 2 ].

Service implications

While not specifically covered in this review, what follows from the findings is the need for services that are able to respond rapidly when the behavior of someone with PWS deteriorates and when a psychotic illness is suspected. A clear diagnostic and treatment pathway should be available in all localities with the necessary expertise to make the diagnosis, particularly distinguishing psychotic illness from the wider PWS neuropsychiatric phenotype, and thereby offering the correct treatment. From the description in some case reports and cohort studies it is also clear that either highly staff-resourced community-based first episode psychosis services or short term psychiatric in-patient care may be needed, with the additional requirement that such environments must be able to manage the food environment. Particularly with the potential effects of psychiatric medications on the drive to eat and subsequent increased weight, the absence of food security would have a serious deleterious effect on physical health.

Availability of data and materials

All data generated or analysed during this study are included in this published article. All data supporting the findings of this study are available within the paper, and more specifically within the tables. All articles on psychosis in PWS have been included in the review, and listed in the tables. Their reference can be found in the bibliography section.

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Acknowledgements

We would like to thank Dr Katherine Manning for her input, and our funder Sam’s research foundation.

Funding for this work has been provided by Sam’s research foundation. PCF is funded by provided by the Bernard Wolfe Health Neuroscience Fund and a Wellcome Trust Investigator Award to PCF (Reference No. 206368/Z/17/Z). All research at the Department of Psychiatry in the University of Cambridge is supported by the NIHR Cambridge Biomedical Research Centre (NIHR203312) and the NIHR Applied Research Collaboration East of England. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

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Aman, L.C.S., Lester, S.D., Holland, A.J. et al. Psychotic illness in people with Prader–Willi syndrome: a systematic review of clinical presentation, course and phenomenology. Orphanet J Rare Dis 19 , 69 (2024). https://doi.org/10.1186/s13023-024-03026-y

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Received : 02 June 2023

Accepted : 11 January 2024

Published : 15 February 2024

DOI : https://doi.org/10.1186/s13023-024-03026-y

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  • Prader–Willi syndrome
  • Cycloid psychosis
  • Atypical psychosis
  • Hallucination
  • Genetic origin of psychosis
  • Early onset psychosis

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