Clozapine Dose Reduction in Remitted Patients With Treatment-Resistant Schizophrenia: A Case Series

Background There is limited evidence on the outcomes of clozapine deprescribing in remitted treatment-resistant schizophrenia (TRS) patients. We present a series of TRS patients in remission who underwent progressive reductions in their maintenance clozapine dose. Study Design This was a retrospective chart review of patients treated with clozapine from March 20, 2014 to March 20, 2024, at the Centre for Addiction and Mental Health, Toronto, Canada. We included patients who met criteria for TRS, were in remission on clozapine, and underwent progressive reduction > 25% in their maintenance dose. Study Results Of the 9 cases included, 4 (44.4%) maintained remission following progressive dose reductions. Two patients (22.2%) relapsed and were hospitalized, while 3 (33.3%) relapsed and required an increase in clozapine dose. Of those who relapsed, 3 had subtherapeutic clozapine levels and one had stopped clozapine before relapse. Overall dose reductions ranged from 100% (complete discontinuation with sustained remission) to 25% (with subsequent dose increase after relapse). The average rate of clozapine reduction was slow across cases, with a median of 25 mg every 12 weeks. Although not statistically significant, patients who maintained remission had slower tapering rates, ranging from 25 mg every 5 weeks to 25 mg every 2 years. Conclusions Reducing the clozapine maintenance dose in remitted TRS patients carried a substantial risk of relapse. The risk may be lower when dose reductions are guided by clozapine levels and implemented gradually over several months to years. Larger samples are needed to identify predictors of relapse in TRS patients undergoing clozapine deprescribing.