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Abstract
Introduction Given the increasing rates of antipsychotic use in multiple psychiatric conditions, greater attention to the assessment, monitoring and documentation of their side effects is warranted. While a significant degree of attention has been provided to metabolic side effect monitoring, comparatively little is known about how clinicians screen for, document and monitor the motor side effects of antipsychotics (ie, parkinsonism, akathisia, dystonia and dyskinesias, collectively ‘extrapyramidal side effects’, EPS). This review aims to systematically assess the literature for insights into current trends in EPS monitoring practices within various mental health settings globally.
Methods and analysis An electronic search will be performed using the OVID Medline, PubMed, Embase, CINAHL and APA PsycINFO databases for studies published in the last quarter century (1998 to present day). Two independent reviewers will conduct the initial title and abstract screenings, using predetermined criteria for inclusion and exclusion. A third reviewer will resolve disagreements if consensus cannot be reached. If selected for inclusion, full-text data extraction will then be conducted using a pilot-tested data extraction form. Quality assessment will be conducted for all included studies using a modified version of the Quality Improvement Minimum Quality Criteria Set. A narrative synthesis and summary of the data will be provided. All stages of the review process will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
Ethics and dissemination Ethical approval is not required. Findings will be peer reviewed, published and shared verbally, electronically and in print with interested clinicians and will also be presented as posters or talks at relevant medical conferences and meetings.
PROSPERO registration number CRD42023482372.
- Systematic Review
- PSYCHIATRY
- Schizophrenia & psychotic disorders
- Protocols & guidelines
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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STRENGTHS AND LIMITATIONS OF THIS STUDY
The search strategy was developed a priori in collaboration with an experienced health sciences librarian and involves a comprehensive search across five large databases and platforms.
The protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines enhancing replicability and transparency.
Included studies will be rated based on their methodological quality using a modified version of the Quality Improvement Minimum Quality Criteria Set quality assessment tool developed by Hempel et al, which is suitable for the quality assessment of various types of service evaluation studies.
Due to resource constraints, the literature search will be restricted to English-only, peer-reviewed publications, possibly increasing the risk of selection bias and limiting the generalisability of review findings.
Introduction
Second generation antipsychotics (SGAs) are broadly used in clinical practice, not only for the treatment of psychotic and bipolar disorders but also for a variety of other conditions.1–3 While SGAs are associated with a lower risk of motor side effects (ie, parkinsonism, akathisia, dystonia and dyskinesias, collectively ‘extrapyramidal side effects’, EPSs) than first-generation antipsychotics the rates of EPS remain significant.4–8 Furthermore, EPSs are associated with impaired quality of life, medication non-adherence, increased morbidity, mortality, caregiver burden, utilisation of healthcare resources and higher medical costs.8–16 This has resulted in some advocating for ‘better monitoring … to assess their true effect on patients’ quality of life and functioning and to prevent underascertainment’,17 something especially important in higher risk populations, for instance, children, adolescents and the elderly.18–20 The most recent American Psychiatric Association’s guidelines (2020) for the treatment of patients with schizophrenia calls for clinical assessment of EPS at baseline or initial assessment, at each subsequent visit as well as an assessment using a ‘structured instrument’ every 6 months in patients at increased risk of tardive dyskinesia and every 12 months for all other patients.21 In the UK, the National Institute for Health and Care Excellence guidelines recommend assessment of any movement disorders before starting antipsychotic medication as part of baseline investigations and to monitor and record side effects of treatment and their impact on functioning, and the emergence of movement disorders, regularly and systematically throughout treatment and especially during titration.22 Unfortunately, evidence demonstrates that actual monitoring rates fall far below these standards.23–25
Rationale for the review
While a significant degree of attention has been provided to metabolic side effect monitoring, with several systematic reviews conducted on the subject,26 27 comparatively little is known about EPS monitoring practices.
When it comes to EPS, its incidence and prevalence in research and naturalistic settings have been thoroughly investigated in numerous studies and reviews.4–6 28 However, there seems to be a paucity of data about current practices relating to how clinicians screen for, monitor and document EPS in patients prescribed antipsychotics. Gaining a better understanding of current practice may allow for the introduction of effective interventions that help address the existing discrepancy between current practice and best practice.
Aim and objectives
The aim of this review is to systematically assess the literature, seeking insights into current EPS monitoring practices within various mental health settings globally.
Our three main objectives are as follows: (1) to identify the extent to which patients prescribed antipsychotic medication receive guideline concordant monitoring, (2) to gather data on interventions that have been proposed to improve this aspect of care and (3) to identify any existing barriers.
Research questions
In accordance with the aim and objectives outlined above, this review will seek to answer the following questions as regards EPS monitoring for patients who are prescribed antipsychotic medication:
Which guidelines if any are being used to guide current practice and arerecommended standards being met? What screening tools are being used?
What is the frequency of monitoring? Has it improved or worsened over the years?
What interventions have been proposed to improve monitoring standards?
What are some of the possible barriers to adequate monitoring?
Methods and design
All stages of the review process including literature searching, screening, applying inclusion and exclusion criteria and data extraction will be reported and documented in accordance with the Preferred Reporting Items for Systematic Review and Met-Analysis Protocol (PRISMA-P) statement.29 The PRISMA-P was used to guide the development of the review protocol (see online supplemental file 1 for PRISMA-P checklist).30 In accordance with the guidelines, this systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under the reference number CRD42023482372. Any amendments to the protocol will be reported when publishing the results.
Supplemental material
Inclusion and exclusion criteria (eligibility of studies)
These are grouped under the following seven subsections:
Study design
Study designs aimed at gathering data on current practices relating to EPS documentation and monitoring as well as studies describing interventions developed to improve clinical performance in the area of documentation and monitoring of EPS will be included in the review. Examples of study designs that will be included are as follows:
Clinical audits without intervention.
Clinical audits with completed audit cycles after intervention.
Service evaluations without a quality improvement intervention.
Service evaluations following a quality improvement intervention.
However, the following study design types will be excluded:
Case reports.
Any trial design, including randomized controlled trials(RCTs).
Literature reviews.
Discussion and viewpoint studies.
Grey literature.
Abstract-only publications.
Epidemiological studies of incidence/prevalence of EPS.
Survey designs.
Types of intervention
All types of interventions concerned with the assessment, screening and monitoring of EPS will be included. This will involve gathering data on the types of processes currently used to carry out EPS monitoring and documentation as well as on any proposed interventions aimed at improving EPS documentation and monitoring such as educational interventions, adoption of novel screening instruments, etc.
Study language
This systematic review will be restricted to English language studies only.
Publication dates
Studies published from 1998 to the present will be included, spanning the last 25 years of clinical practice. We consider this sufficiently representative of contemporary trends in practice.
Study population/demographics
The first population of interest includes patients of all ages and genders receiving treatment for one or more mental health conditions and prescribed one or more antipsychotic medications. While it is true that EPS can manifest spontaneously in patients who were never exposed to antipsychotic agents31 32 or can be caused by substances other than antipsychotics,33–35 a substantial proportion of reported EPS is attributed to antipsychotic medication.6 36 37 Moreover, even within cohorts of previously neuroleptic naïve patients, research suggests that dopamine D2 receptor antagonist antipsychotics interact with the disease process in such a way that ‘precipitates’ and ‘accentuates’ movement disorders intrinsic to schizophrenia’.38 This review will, therefore, focus on patients prescribed antipsychotic medication, as they may be at higher risk of developing severe EPS. In addition, most available guidelines on EPS monitoring specifically refer to patients prescribed antipsychotic medications.
The second population of interest includes the healthcare professionals involved in the care of the patients (eg, nurses, residents, clinicians and pharmacists) and tasked with carrying out EPS monitoring.
Study settings
Studies reporting on EPS monitoring practices in any naturalistic, real-world clinical setting, including inpatient hospitals, day hospitals, outpatient clinics, community settings, etc will be included.
Other phenomena of interest
Where available, data on the views, experiences and behaviours of healthcare professionals and patients involved in the assessment, screening and monitoring of EPS will also be collected.
Patient and public involvement
Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this protocol.
Information sources
Electronic sources
The literature search was conducted using the following five databases and search platforms: OVID Medline, PubMed, EMBASE, PsycINFO and CINAHL. The initial search covers 25 years and includes studies published between April 1998 and April 2023. These searches will be re-run immediately prior to the final analysis (projected to take place in September 2024) and potential further studies will be retrieved for inclusion, ensuring that the most up-to-date information is presented in the review. The reference lists of all eligible articles will be manually searched to identify any additional relevant citations to ensure a comprehensive search.
Search strategy
Review authors RA and RS (librarian and information specialist with expertise in electronic searching) developed and ran a comprehensive search strategy. A scoping search was undertaken against each database to inform how the search terms were being translated and hence to identify the corresponding text words in each database. Following this, the complete search strategy was tested for its sensitivity to locate the key papers that the researchers are already aware of, along with relevant articles which are consistent with the inclusion criteria just before running the search through all the selected search engines.
The search strategy used variations in text words found in the title, abstract or keyword fields, and relevant focused subject headings to retrieve articles combining the following three search concepts, linked by the Boolean operator ‘AND’:
(1) One or more medication terms: antipsychotic* OR psychotropic* OR haloperidol OR olanzapine OR quetiapine OR risperidone OR cariprazine OR amisulpride OR aripiprazole OR lurasidone etc… (to include full list of antipsychotic medication listed as per the WHO Collaboration Centre for Drug Statistics Methodology ATC classification).
AND
(2) One or more EPS terms: “Extrapyramidal symptom*” OR “Extrapyramidal side effect*” OR “drug-induced movement disorder*” OR ‘Drug-Related Side Effects and Adverse Reactions’ OR ‘movement side effects’ OR Dystonia OR ‘acute dystonia’ OR parkinsonism OR ‘drug-induced parkinsonism’ OR akathisia OR “tardive dyskinesia” OR tremor
AND
(3) One or more terms relating to monitoring, screening, documenting or auditing clinical practice (including screening instruments): ‘Monitoring’ OR ‘Screening’ OR ‘Documenting’ OR ‘Documentation’ OR ‘Assessing’ OR ‘Assessment’ OR ‘Abnormal Involuntary Movement Scale’ OR ‘Extrapyramidal Symptom Rating Scale’ OR ‘Simpson-Angus Scale’ OR ‘Barnes Akathisia Scale’.
The search included all relevant synonyms, truncations and Mesh terms. Full details of search terms used for the OVID Medline search are shown in online supplemental file 2. A similar search was conducted using the other databases and search platforms. The full search strategy is available on request from the corresponding author.
Supplemental material
Study records
Data management
The search results will be uploaded into web-based, systematic review management software (Covidence). Duplicates will be removed automatically by Covidence software. Authors RA and MM will scan through the results to remove any remaining duplicate records manually. Using Covidence, the initial title and abstract screening, and the full-text review will be logged. All standardised forms will be piloted and revised as needed by the reviewers before starting the review.
Screening and selection process
After identification of articles from searching the electronic databases, titles and abstracts will be screened independently by two review authors according to the predefined eligibility criteria. Disagreements will be resolved by consensus and the opinion of a third reviewer will be sought if necessary. The full-text copies of each potentially relevant study will then be retrieved and screened independently by at least two reviewers including the first author (RA). Consensus will be reached through discussion, and in the event that no consensus can be reached for a study, a third reviewer will arbitrate. All studies not meeting the eligibility criteria will be excluded. The results will be reported using the PRISMA flow diagram.
Data extraction and reporting of results
A standardised data extraction form will be developed to extract all relevant data from included studies. Information to be extracted will be as follows:
Study characteristics: authors, date, settings, country of origin, study design and sample size.
Patient characteristics: demographic data (age, gender, diagnosis, type of antipsychotic prescribed, etc.).
Monitoring characteristics: frequency, use of a structured tool, healthcare professionals involved in monitoring, guidelines followed, etc.
Intervention characteristics: (if study incorporated a preintervention/postintervention design): educational intervention, adoption of a new instrument, etc.
The data extraction form will be piloted on a small random sample (n=3) of the illegible studies to assess its reliability in extracting the targeted study data. Review authors TH, MB and SK will each independently conduct data extraction on the three studies. Review authors RA and MM will then review this extracted data, checking against the full text of the three studies for any discrepancies (eg, errors, omissions or failure to have consensus in any area) and will decide on how to resolve any that may arise. If the above pilot data extraction process is deemed reliable then the review authors TH, MB and SK will each independently conduct data extraction on the remaining studies in the systematic review. Review authors RA and MM will then cross-check the extracted data against the full-text articles in a similar process to that highlighted above.
Additionally, study authors will be contacted if necessary to gain information for clarification purposes and access to raw material when needed.
Critical appraisal of study quality
Authors RA and MM will use the Quality Improvement Minimum Quality Criteria Set (QI-MQCS) developed by Hempel et al to conduct the quality assessment of included studies.39 Disagreements will be resolved by consensus; the opinion of a third reviewer (MG) will be sought if necessary. The QI-MQCS is a 16-domain, validated, reliable critical appraisal tool that assesses expert-endorsed QI domains for studies that include a QI intervention component. The QI-MQCS will be modified to be suitable for the body of studies included in our review, and in particular, to be able to assess studies with no intervention component, that is, clinical audits and service evaluations with no intervention. This will involve accepting a broader definition of several domains of the appraisal instrument to include studies evaluating existing services or standards in addition to QI intervention. This approach was chosen in the absence of a suitable tool for critical appraisal of service evaluation studies with no intervention component.
The QI-MQCS tool is designed to provide a score for each domain as well as a total score, which is expressed as a percentage of the maximum possible score.
Analysis
Data synthesis
In this review, the search is expected to reveal heterogeneous studies and meta-analysis of study findings is therefore not a study objective. Therefore, data synthesis will take the form of a structured narrative synthesis of the included studies. The defining characteristic of a narrative synthesis is that it adopts a textual approach to the process of synthesis in order to provide answers to the identified research questions in a structured manner. Study findings pertaining to the following three themes will be examined and synthesised: (1) Data concerning the extent and quality of EPS monitoring being carried out in various mental health settings will be summarised. (2) Following this, details about any potential interventions employed to improve monitoring practices will be synthesised. And finally, (3) Information about any identifiable barriers or facilitators to guideline concordant EPS monitoring will be synthesised and discussed.
Study status
The study is ongoing and is expected to be completed by September 2024.
Proposed value of the systematic review and use of the findings
This systematic review seeks to shed light on the existing patterns of EPS monitoring occurring within various mental health settings. The findings of this systematic review may be of interest to mental health organisations and services as they are expected to provide insights into the potential barriers or facilitators (including possible quality improvement interventions) influencing whether EPS monitoring is carried out in a guideline concordant manner. This may in turn encourage organisations and services to assess their existing EPS monitoring practice and/or lead them to consider the adoption or development of interventions to improve monitoring standards.
Ethics statements
Patient consent for publication
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors RA is the author acting as guarantor. The study was conceived by RA, MS, MM and TH. RA and MM developed the eligibility criteria, search strategy, quality assessment strategy and data extraction plan with guidance from MS and RS. RA, TH and MM wrote the manuscript. MS, MB, MM, MG, JH, SK and CC read all drafts of the manuscript, provided feedback and approved the final manuscript. All contributors meet the ICMJE criteria for authorship.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests MS has received honoraria/has been a consultant for AbbVie, Angelini, Lundbeck, Otsuka.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.