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 (maximum¼100 mg/day) on day 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