Serum concentrations of clozapine and its major metabolites: effects of cotreatment with fluoxetine or valproate

Am J Psychiatry. 1994 Jan;151(1):123-5. doi: 10.1176/ajp.151.1.123.

Abstract

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Clozapine / analogs & derivatives
  • Clozapine / blood*
  • Clozapine / metabolism
  • Clozapine / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Fluoxetine / blood
  • Fluoxetine / pharmacology*
  • Fluoxetine / therapeutic use
  • Humans
  • Male
  • Psychotic Disorders / blood*
  • Psychotic Disorders / drug therapy
  • Schizophrenia / blood
  • Schizophrenia / drug therapy
  • Stimulation, Chemical
  • Valproic Acid / blood
  • Valproic Acid / pharmacology*
  • Valproic Acid / therapeutic use

Substances

  • Fluoxetine
  • norclozapine
  • Valproic Acid
  • Clozapine