Effect of fluoxetine on the plasma concentrations of clozapine and its major metabolites in patients with schizophrenia.
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.
Institute of Pharmacology, University of Messina, Italy.
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D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage* / Q000009:adverse effects; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001711:Biotransformation; D002908:Chronic Disease; D003024:Clozapine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D003863:Depression / Q000188:drug therapy / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy / Q000201:enzymology*
D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D005473:Fluoxetine; D019363:Cytochrome P-450 CYP1A1; D003024:Clozapine