Pharmacopsychiatry 1997; 30(6): 266-270
DOI: 10.1055/s-2007-979505
Case Reports

© Georg Thieme Verlag Stuttgart · New York

Dose-Dependent Pharmacokinetic Interaction of Clozapine and Paroxetine in an Extensive Metabolizer

A. A. B. Joos1 , F. König1 , U. G. Frank1 , W. P. Kaschka1 , K. E. Mörike2 , R. Ewald3
  • 1University of Ulm, Department of Psychiatry I, Ravensburg-Weissenau, Germany
  • 2Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany
  • 3Medical Department/CNS, Sandoz-Wander, Nürnberg, Germany
Further Information

Publication History

Publication Date:
20 April 2007 (online)

A 53-year-old patient suffering from delusional disorder developed an anticholinergic syndrome 19 days after initiation of paroxetine in addition to a steady dose of clozapine. The clozapine plasma concentration had doubled and was in the toxic range. On re-exposition with a lower clozapine dosage the increase was significantly lower. The importance of a dose-dependent interaction of both drugs is emphasized and a possible pharmacological explanation described. With regard to interactions of SSRIs and clozapine, fluvoxamine, a potent inhibitor of cytochrome P4501A2, gives rise to higher clozapine levels at an earlier time, compared to other SSRIs (paroxetine, fluoxetine and sertraline), which are potent cytochrome P4502D6 inhibitors.