Am J Psychiatry 1996; 153:820-822
Copyright © 1996 by American Psychiatric Association
Serum levels of clozapine and norclozapine in patients treated with selective serotonin reuptake inhibitors
F Centorrino, RJ Baldessarini, FR Frankenburg, J Kando, SA Volpicelli and JG Flood
Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
OBJECTIVE: The selective serotonin reuptake inhibitor (SSRI) fluoxetine can
increase serum levels of clozapine and norclozapine, but effects of other
SSRIs are unknown. Thus, the authors evaluated interactions of clozapine
with fluoxetine, paroxetine, and sertraline. METHOD: Serum clozapine and
norclozapine concentrations were assayed in 80 psychiatric patients,
matched for age and clozapine dose, given clozapine (mean dose = 279
mg/day) alone or with fluoxetine (mean dose = 39.3 mg/day), paroxetine
(mean = 31.2 mg/day), or sertraline (mean = 92.5 mg/ day). Each patient's
dose of clozapine was stable for at least a month before serum sampling.
RESULTS: Concentrations of clozapine plus norclozapine averaged 43% higher,
and the risk of levels higher than 1000 ng/ml was 10-fold greater (25%), in
the patients taking SSRIs, with minor differences between patients taking
the individual SSRIs. CONCLUSIONS: SSRIs can increase circulating
concentrations of clozapine and norclozapine, sometimes to potentially
toxic levels.
