Clinical guidelines recommend slow clozapine dose titration, a procedure introduced in the 1980's to decrease the risk of drug-induced seizures and hypotension. The procedure is considered safe, but may delay adequate control of symptoms.

To evaluate the effectiveness and safety of rapid clozapine dose titration in schizophrenia patients at high risk of harming themselves or others.

The rapid clozapine dose titration was used for a consecutive cohort of schizophrenia patients (N = 111, mean age 42.1%, 52% males) admitted to a single psychiatric hospital. Clozapine was started with a dose of 12.5–25 mg and additional doses of 25–50 mg where given as needed every 6 hours. The clozapine treatment was intiated on admission for 73 patients who had been treated with clozapine in the past (Group 1). Thirty-eight patients received clozapine after failing to respond to other antipsychotics (Group 2).

Admission PANSS scores were similar in the 2 groups (104.3 ± 2.9 vs. 103.8 ± 5.1, p = 0.48). Symptom control was obtained after 4.1 ± 3.1 days with a maximum dose of 352.7 ± 176.1 mg clozapine/day in group 1 and after 7.1 ± 4.8 days (p < 0.001) with a maximum dose of 408.6 ± 187.5 mg clozapine/day (p = 0.12) in Group 2. The PANSS scores at discharge indicated similar reduction in symptom severity (60.5 ± 5.4 vs. 59.8 ± 7.4, p = 0.539). None of the patients treated had seizures, syncope, neutropenia or other significant adverse events.

Rapid clozapine dose titration appears safe and effective when used in schizophrenia patients with or without prior exposure to the drug.