What is the extent of research assessing patients’ and clinicians’ perspectives on clozapine treatment? – a comprehensive scoping review

Background The atypical antipsychotic clozapine is the gold standard for treating treatment-resistant schizophrenia; however, it is continuously underutilized in most parts of the world. A few systematic reviews addressing barriers to clozapine prescribing have previously been conducted, primarily focusing on clinical staff’s attitudes and perceived barriers to prescribing. However, a preliminary literature search revealed that additional literature on the subject does exist, including literature on patient perspectives, without having been included in any of the former reviews. It is therefore difficult to conclude if the former synthesizes of the literature are representative of current evidence, and if the topic has been adequately investigated to inform clinical practice. A scoping review is warranted to map and synthesize a broader scope of primary studies on patients’ and/or clinicians’ perspectives on clozapine treatment to identify any gaps for future research. Methods The electronic databases Cochrane Library, CINAHL, Web of Science, Psychinfo, MEDLINE, and EMBASE were searched, supplied with searches of Google Scholar, The Networked Digital Library of Theses and Dissertations (NDLTD), and OpenGrey. Citation tracking of selected studies was furthermore undertaken. Two researchers independently screened and extracted the data. Registration PROSPERO does not offer registration of scoping reviews; however, the protocol was prospectively registered with the Open Science Framework and subsequently published as an article. Results One hundred and forty-six studies were included. Most studies reported upon patients’ or clinicians’ perspectives on active clozapine treatment or on clinicians’ general perspectives on barriers to clozapine initiation. Three apparent gaps in research were identified: 1) clozapine eligible, yet clozapine-naïve, outpatients’ attitudes towards clozapine commencement, 2) assessments of clinicians’ reasons for clozapine withholding and perceived facilitators of clozapine treatment in specific patient-cases, and 3) direct assessments of both patient and clinician perspectives on clozapine discontinuation, continuation and re-challenge in specific patient-cases. Conclusions Research regarding perspectives on clozapine treatment tends to repeat itself. Future studies addressing the identified gaps in evidence are warranted and could provide the insights needed to optimize clozapine utilization. Strengths and limitations of this study: ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work is part of a Ph.D. project funded by the Mental Health Services of Region Zealand Psychiatry East, Roskilde, Denmark, The Psychiatric Research Unit, Region Zealand Psychiatry West, Slagelse, Denmark, and the Psychiatric Centre Glostrup, Unit for Complicated Schizophrenia, Mental Health Services of The Capital Region of Denmark, in collaboration. Grant numbers are not applicable. Region Zealand Psychiatry received, from a former patient, a bequeathed donation favoring patient-oriented research within the region. The Ph.D. project in question, and hence this study, is partially funded by that donation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the findings of this study are retrievable from the data repository The Open Science Framework (OSF) at or available as supplementary materials attached to the article.