Pharmacopsychiatry 2002; 35(2): 50-56
DOI: 10.1055/s-2002-25026
Original Paper
© Georg Thieme Verlag Stuttgart · New York

The Effect of Fluoxetine on the Pharmacokinetics and Safety of Risperidone in Psychotic Patients

G.  Bondolfi1, 2 , C.  B.  Eap1 , G.  Bertschy2 , D.  Zullino1 , A.  Vermeulen3 , P.  Baumann1
  • 1Département universitaire de psychiatrie adulte, Site de Cery, Prilly-Lausanne, Switzerland
  • 2Département de psychiatrie, Hôpitaux Universitaires de Genève, Geneva, Switzerland
  • 3Janssen Research Foundation, Beerse, Belgium
Further Information

Publication History

3. 1. 2001

29. 6. 2001

Publication Date:
12 April 2002 (online)

In this open, 30-day trial, the pharmacokinetics, safety and tolerability of a combination therapy of risperidone (4 or 6 mg/day) and fluoxetine (20 mg/day from day 6) were evaluated in 11 psychotic inpatients. CYP2D6 genotyping revealed that 3 and 8 patients were poor metabolizers (PMs) and extensive metabolizers (EMs) of debrisoquine, respectively. The mean (± SD) AUC of risperidone increased from 83.1 ± 46.8 ng.h/ml and 398.3 ± 33.2 ng.h/ml (monotherapy) to 345.1 ± 158.0 ng.h/ml (p < 0.05) and 514.0 ± 144.2 ng.h/ml (p < 0.001) when coadministered with fluoxetine in EMs and PMs, respectively. The AUC of the active moiety (risperidone plus 9-hydroxy-risperidone) increased from 470.0 ± 170.0 ng.h/ml to 663.0 ± 243.3 ng.h/ml (p < 0.05) and from 576.3 ± 19.6 ng.h/ml to 788.0 ± 89.1 ng.h/ml (ns) in EMs and PMs, respectively. In EMs, the AUC of 9-hydroxy-risperidone remained similar (monotherapy vs. combination therapy: 386.8 ± 153.0 ng.h/ml vs. 317.7 ± 125.2 ng.h/ml, ns), whereas it increased in PMs (178.3 ± 23.5 ng.h/ml vs. 274.0 ± 55.1 ng.h/ml (p < 0.05)). Ten of the 11 patients showed a clinical improvement (reduction of 20 % or more in total PANSS score and 70 % on the mean MADRS score compared to baseline). The severity and incidence of extrapyramidal symptoms and adverse events did not significantly increase when fluoxetine was added.

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G. Bondolfi, M.D. 

Département de psychiatrie
Hôpitaux Universitaires de Genève

Boulevard de St. Georges 16-18

CH- 1205 Geneva/Switzerland

Phone: +41 (22) 327 75 55, +41 (22) 344 40 74 (Home)

Fax: +41 (22) 327 75 99

Email: guido.bondolfi@hcuge.ch

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