Rapid clozapine titration in treatment-refractory bipolar disorder

Background: Clozapine is effective in treatment-refractory bipolar disorder (BD). Guidelines recommend slow titration to prevent seizures, hypotension and myocarditis, but this stance is not supported by comparative data. Objective: To evaluate the safety and effectiveness of rapid clozapine titration in BD. Methods: Analysis of a consecutive cohort of treatment-refractory BD patients with mixed/manic episode admitted on alternate days to one of two units of a psychiatric hospital. On one unit, clozapine was started at 25 mg followed by 25-50 mg as needed every 6 h (maximum 100 mg/day) on clay 1, followed by increases of 25-100 mg/day. On the other unit, clozapine was initiated with 25 mg in day 1, followed by increases of 25-50 mg/day. The primary outcome was the number of days from starting clozapine until readiness for discharge, adjusted in logistic regression for the number of antipsychotics tried during the hospitalization, psychotropic co-treatments and presence of psychotic features. Results: Patients subject to rapid (N = 44) and standard (N = 23) titration were similar in age, gender, smoking status, body mass index, illness severity at baseline and discharge, and highest clozapine dose. Clozapine was discontinued due to hypotension (N = 1) and pneumonia (N = 1) during rapid titration, and for excessive sedation (N = 1) in each titration group. The number of hospital days from starting clozapine until readiness for discharge was 3.8 days shorter in the rapid titration group (12.7 +/- 6.3 vs. 16.5 +/- 5.8, p = 0.0077). Conclusion: Rapid clozapine titration appeared safe and effective for treatment-refractory BD. The potential for shorter hospital stays justifies prospective trials of this method. (C) 2014 Elsevier B.V. All rights reserved.