Effect of fluoxetine on the plasma concentrations of clozapine and its major metabolites in patients with schizophrenia

Edoardo Spina, Angela Avenoso, Gabriella Facciolà, Michele Fabrazzo, Palmiero Monteleone, Mario Maj, Emilio Perucca, Achille P. Caputi

Research output: Contribution to journalArticlepeer-review

Abstract

The effect of fluoxetine on the plasma concentrations of clozapine and its major metabolites was studied in 10 schizophrenic patients with residual negative symptoms. Patients stabilized on clozapine therapy (200-450 mg/day) received additional fluoxetine (20 mg/day) for eight consecutive weeks. During fluoxetine administration, mean plasma concentrations of clozapine, norclozapine and clozapine N-oxide increased significantly by 58%, 36% and 38%, respectively. There was no difference in negative symptomatology, as measured by the Scale for Assessment of Negative Symptoms, and the drug combination was generally well tolerated. The concomitant elevation in plasma levels of clozapine and its major metabolites suggests that fluoxetine inhibits the metabolism of clozapine by affecting pathways other than N- demethylation and N-oxidation. Close monitoring of clinical response and, possibly, plasma clozapine levels is recommended whenever fluoxetine is given to patients stabilized on clozapine therapy.

Original languageEnglish
Pages (from-to)141-145
Number of pages5
JournalInternational Clinical Psychopharmacology
Volume13
Issue number3
DOIs
Publication statusPublished - 1998

Keywords

  • Clozapine
  • CYP1A2
  • CYP2D6
  • Drug interaction
  • Fluoxetine
  • Negative symptoms
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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