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

BackgroundThe 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 staffs 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. MethodsThe 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. RegistrationPROSPERO does not offer registration of scoping reviews; however, the protocol was prospectively registered with the Open Science Framework and subsequently published as an article. ResultsOne 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-naive, 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. ConclusionsResearch 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 studyO_LIThe prospective registration and publication of the review protocol has ensured transparency of the review process. C_LIO_LIThe search strategy has ensured a comprehensive search of the literature and multiple booster searches on Google Scholar have ensured a continued update on the scope of literature, the most recent one in January 2024. C_LIO_LIThe original literature search was conducted in June 2021. C_LIO_LIThe search was restricted to publications in the English language, which may have precluded the identification of some relevant insights and studies. C_LI