Am J Psychiatry 1994; 151:123-125
Copyright © 1994 by American Psychiatric Association
Serum concentrations of clozapine and its major metabolites: effects of cotreatment with fluoxetine or valproate
F Centorrino, RJ Baldessarini, J Kando, FR Frankenburg, SA Volpicelli, PR Puopolo and JG Flood
Department of Psychiatry, Harvard Medical School, Boston, MA.
Serum concentrations of clozapine, norclozapine, and clozapine-N-oxide were
assayed in psychotic patients treated with clozapine alone (N = 17),
clozapine with fluoxetine added (N = 6), or clozapine with valproic acid
added (N = 11). Subjects were matched for age and other treatments, and
concentrations were corrected for daily dose of clozapine (milligrams per
kilogram of body weight). With valproic acid, there was a minor increase in
total clozapine metabolites, which was even less with dose correction.
Fluoxetine increased all clozapine analytes, in some cases to twice the
levels in the subjects given only clozapine.
