Intramuscular Clozapine: A Systematic Scoping Review of Clinical Feasibility, Safety, and Efficacy

The use of oral clozapine for treatment-resistant schizophrenia (TRS) is often limited by acute psychotic symptoms and medical instability. Intramuscular (IMI) clozapine has been infrequently used as a bridge to oral therapy. This literature review considers the available evidence regarding IMI clozapine's feasibility, effectiveness, and safety.

A systematic scoping review with a protocol preregistered on the OSF Registry. Records extracted from Ovid MEDLINE, CINAHL, Embase, PsycInfo, Web of Science Core Collection, Scopus, CENTRAL, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and Google Scholar. Risk of bias and quality assessments were conducted.

Twenty records met the inclusion criteria, primarily consisting of case reports or series; no randomized trials were identified. Half of the included studies were rated as either "fair" or "good" quality (n=11/20). Most records addressed the initiation of clozapine in the context of oral (PO) refusal, with services describing IMI clozapine as feasible within strict governance guidelines and pharmacy support. IMI clozapine was reported to provide a bridge to PO administration, with transitions commonly occurring within days, and the use of coercive measures decreasing over time. Patient-reported data were limited; however, safety profiles mirrored those of oral clozapine; route-specific adverse effects were localized, and serious events were infrequently reported.

The existing literature suggests that IMI clozapine may be used as a time-limited intervention to support continued PO administration. Further prospective studies with standardized procedures, patient-centered outcomes, and extended follow-up periods are necessary to inform clinical practice and policy development.