Clozapine prescribing in treatment-resistant schizophrenia – an updated systematic literature review of barriers and facilitators among clinicians

BACKGROUND: Increased rates of clozapine prescribing are essential to improving timely patient access within treatment-resistant schizophrenia (TRS) management. The extent of geographical variation in its use suggests it is possible to develop interventions to increase clinician engagement. To inform intervention development, a contemporary review of barriers and facilitators to increased clozapine prescribing is required. We aimed to conduct a systematic review of research addressing barriers and facilitators to clozapine prescribing among clinicians within TRS management. METHODS: The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, CINAHL, and PsycINFO were searched from inception to July 2025. Results were synthesized qualitatively. RESULTS: Fifteen studies were included. Barriers related to clinicians, patients and carers, and healthcare institutions. Primary clinician-related barriers included insufficient knowledge of, and confidence in, managing clozapine treatment and the associated administrative burden. Primary patient-related barriers included concerns regarding patients' willingness to consistently adhere to clozapine treatment and associated monitoring requirements. A lack of dedicated systems of care to facilitate clozapine initiation and shared community care were the leading institutional barriers. Major facilitators included improved education for clinicians, access to point-of-care testing, and increased availability of dedicated clozapine clinics. CONCLUSION: Most barriers to systematically increasing clozapine prescribing rates are beyond the influence of individual prescribers. Instead, structural interventions focusing on (i) reducing the administrative burden associated with establishing clozapine treatment, (ii) increasing access to standardised training and supervision opportunities, and (iii) providing longitudinal support to clinicians when managing clozapine treatment, are required.