Clozapine Discontinuation and Treatment Engagement in Patients with Schizophrenia: A Retrospective Cohort Study from a Tertiary Care Centre in India

Background: Clozapine is the evidence-based treatment of choice for treatment-resistant schizophrenia, yet premature discontinuation and loss to follow-up remain major barriers to sustained benefit, particularly in low- and middle-income country settings. We examined real-world rates, timing, reasons, and predictors of clozapine discontinuation and care disengagement in a government-run tertiary psychiatric facility in India. Aim: To examine the rates, timing, reasons, and predictors of clozapine discontinuation and care disengagement among patients initiated on clozapine in a tertiary psychiatric center in India. Materials and Methods: We conducted a single-center retrospective cohort study where adult patients (≥18 years) with schizophrenia or schizoaffective disorder initiated on clozapine between January 2017 and December 2023 were followed for up to 12 months from initiation. Clozapine discontinuation was defined as permanent cessation or a dispensing gap >60 days; care disengagement was defined as no documented clinical contact for ≥90 days beyond the expected follow-up date. Multivariable Cox proportional hazards regression models were used to identify independent predictors of discontinuation and care disengagement. Results: Among 544 patients initiated on clozapine, 148 (27.2%) discontinued treatment and 77 (14.2%) disengaged from care within 12 months. Discontinuation clustered early: 12.3% occurred by month 3 and 19.7% by month 6; disengagement similarly concentrated early (5.1% by month 3; 9.0% by month 6). The most commonly documented reason for discontinuation was adverse effects (32.4%), followed by monitoring/follow-up difficulties (19.6%) and nonadherence (12.8%). In adjusted analyses, discontinuation was independently associated with comorbid substance use (hazard ratio [HR]: 1.62, 95% confidence interval [CI]: 1.18–2.22), greater distance from the facility (HR per 10 km 1.08, 95% CI: 1.03–1.13), and adverse effects requiring dose modification (HR: 1.89, 95% CI: 1.34–2.66), while inpatient initiation was protective (HR: 0.74, 95% CI: 0.56–0.99). Care disengagement was also associated with substance use (HR: 1.54, 95% CI: 1.01–2.35) and distance (HR per 10 km: 1.12, 95% CI: 1.05–1.20), with inpatient initiation protective (HR: 0.68, 95% CI: 0.47–0.98). Conclusion: In this Indian tertiary care cohort, approximately one in four patients discontinued clozapine and one in seven disengaged from care within a year, predominantly in the first 6 months. Early-phase tolerability management, integrated substance-use care, and service delivery models that reduce travel and monitoring burden may improve retention and outcomes.