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The effect of fluoxetine on the pharmacokinetics and safety of risperidone in psychotic patients

(2002) PHARMACOPSYCHIATRY. 35(2). p.50-56
Author
Organization
Abstract
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 I I 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 I I 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.
Keywords
DOUBLE-BLIND, POOR METABOLIZERS, DEPRESSION, 9-HYDROXYRISPERIDONE, VENLAFAXINE, FLUVOXAMINE, PLASMA-CONCENTRATIONS, SCHIZOPHRENIC-PATIENTS, CYTOCHROMES P450 2D6, SEROTONIN REUPTAKE INHIBITORS

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Chicago
Bondolfi, G, CB Eap, G Bertschy, D Zullino, An Vermeulen, and P Baumann. 2002. “The Effect of Fluoxetine on the Pharmacokinetics and Safety of Risperidone in Psychotic Patients.” Pharmacopsychiatry 35 (2): 50–56.
APA
Bondolfi, G., Eap, C., Bertschy, G., Zullino, D., Vermeulen, A., & Baumann, P. (2002). The effect of fluoxetine on the pharmacokinetics and safety of risperidone in psychotic patients. PHARMACOPSYCHIATRY, 35(2), 50–56.
Vancouver
1.
Bondolfi G, Eap C, Bertschy G, Zullino D, Vermeulen A, Baumann P. The effect of fluoxetine on the pharmacokinetics and safety of risperidone in psychotic patients. PHARMACOPSYCHIATRY. 2002;35(2):50–6.
MLA
Bondolfi, G, CB Eap, G Bertschy, et al. “The Effect of Fluoxetine on the Pharmacokinetics and Safety of Risperidone in Psychotic Patients.” PHARMACOPSYCHIATRY 35.2 (2002): 50–56. Print.
@article{4325576,
  abstract     = {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 I I 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 {\textlangle} 0.05) and 514.0 +/- 144.2 ng.h/ml (p {\textlangle} 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 {\textlangle} 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 {\textlangle} 0.05)). Ten of the I I 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.},
  author       = {Bondolfi, G and Eap, CB and Bertschy, G and Zullino, D and Vermeulen, An and Baumann, P},
  issn         = {0176-3679},
  journal      = {PHARMACOPSYCHIATRY},
  keyword      = {DOUBLE-BLIND,POOR METABOLIZERS,DEPRESSION,9-HYDROXYRISPERIDONE,VENLAFAXINE,FLUVOXAMINE,PLASMA-CONCENTRATIONS,SCHIZOPHRENIC-PATIENTS,CYTOCHROMES P450 2D6,SEROTONIN REUPTAKE INHIBITORS},
  language     = {eng},
  number       = {2},
  pages        = {50--56},
  title        = {The effect of fluoxetine on the pharmacokinetics and safety of risperidone in psychotic patients},
  url          = {http://dx.doi.org/10.1055/s-2002-25026},
  volume       = {35},
  year         = {2002},
}

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