The effect of fluoxetine on the pharmacokinetics and safety of risperidone in psychotic patients.
In this open, 30-day trial, the pharmacokinetics, safety and tolerability of a combination therapy of risperidone (4 or 6 mg/day)and fluoxetine (20mg/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.
Bondolfi
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Dépatrement universitaire de psychiatrie adulte, Site de Cery, Pirlly-Lausanne, Switzerland. guido.bondolfi@hcuge.ch
Eap
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CB
Bertschy
G
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Zullino
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D
Vermeulen
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A
Baumann
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P
D000293:Adolescent; D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects* / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D019389:Cytochrome P-450 CYP2D6 / Q000096:biosynthesis; D004347:Drug Interactions; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects* / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000378:metabolism* / Q000523:psychology; D018967:Risperidone / Q000009:adverse effects* / Q000493:pharmacokinetics*; D013557:Switzerland
D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents; D005473:Fluoxetine; D019389:Cytochrome P-450 CYP2D6; D018967:Risperidone