Brief ReportsFluvoxamine Augmentation of Olanzapine in Chronic Schizophrenia: Pharmacokinetic Interactions and Clinical EffectsHiemke, Christoph PhD*; Peled, Avi MD†‡; Jabarin, Mahmoud MD†‡; Hadjez, Jack MD†‡; Weigmann, Harald MD, PhD*; HÄrtter, Sebastian PhD*; Modai, Ilan MD, MHA‡§; Ritsner, Michael MD, PhD‡§; Silver, Henry MBBS, BMedS, DPM, FRANZCP†‡§ Author Information *Department of Psychiatry, University of Mainz, Mainz, Germany; †Brain Behavior Laboratory and ‡Institute of Psychiatric Studies, Sha’ar Menashe Mental Health Center, Hefer, Israel; and §Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel Received July 19, 2001; accepted December 26, 2001. Address requests for reprints to: Henry Silver, MBBS, BMedS, DPM, FRANZCP, Deputy Director, Sha’ar Menashe Mental Health Center, Mobile Post Hefer 38814, Israel. Address e-mail to: [email protected]. Journal of Clinical Psychopharmacology 22(5):p 502-506, October 2002. Buy Abstract Olanzapine is a substrate of the cytochrome P450 enzyme (CYP) 1A2. In this study, pharmacokinetic interactions and clinical effects of adding the CYP1A2 inhibitor fluvoxamine to steady-state olanzapine was examined in patients suffering from schizophrenia. Eight patients had been treated for at least 3 months with 10 to 20 mg/day olanzapine. Fluvoxamine (100 mg/day) was added (week 0) to the olanzapine treatment and continued for 8 weeks. Concentrations of olanzapine and its metab-olite N-desmethylolanzapine and of fluvoxamine were analyzed at weeks 0, 1, 4, and 8. Addition of fluvoxamine resulted in a 12% to 112% (p < 0.01) increase of olanzapine from 31 ± SD 15 ng/mL (week 0) to 56 ± 31 ng/mL (week 8) in all patients. N-desmethylolanzapine concentrations were not significantly changed (p > 0.05). Fluvoxamine concentrations were 48 ± 26 ng/mL on week 1 and 83 ± 47 ng/mL on week 8. It is concluded that fluvoxamine affects olanzapine degradation and thus increases olanzapine concentrations. Although the combination was well tolerated in this sample and the negative symptom response appeared to be favorable in at least five patients, the combination therapy of olanzapine and fluvoxamine should be used cautiously and should be controlled by therapeutic drug monitoring to avoid olanzapine-induced side effects or intoxications. © 2002 Lippincott Williams & Wilkins, Inc.