Clinical Drug Investigation

, Volume 19, Issue 4, pp 283–292 | Cite as

Risperidone Drug Monitoring

A Useful Clinical Tool?
  • Pascal Odou
  • J. C. Levron
  • M. Luyckx
  • C. Brunet
  • Hugues Robert
Clinical Pharmacodynamics


Background: Risperidone is an atypical antipsychotic drug that has been marketed in France since 1996. Therapeutic failures have been observed with risperidone.

Objective: To investigate whether interactions with the cytochrome P450 (CYP) isoenzymes implicated in risperidone metabolism could explain these treatment failures.

Design and Setting: This was a retrospective study of clinical and drug monitoring data from 50 patients treated by five psychiatrists in northern France.

Methods: The concentration of active drug (risperidone + 9-hydroxy-risperidone) in serum was evaluated by high performance liquid chromatography and radio receptor assay. Clinical efficacy was assessed by the global improvement (CGI2) item of the Clinical Global Impression rating scale.

Results: Statistical analysis revealed a significant increase in efficacy when the serum concentration of active drug was between 25 and 150 μg/L compared with when it was out of this range. Carbamazepine, a CYP3A4 inducer, dramatically decreased the concentration of the active moiety of risperidone; on the contrary, CYP3A4 inhibitors (alprazolam and valproic acid) increased the concentration of active drug. The metabolism of risperidone by CYP3A4 did not lead to the formation of metabolite(s) with anti-D2 dopaminergic activity. Drugs interacting with CYP2D6 altered the risperidone/9-hydroxy-risperidone ratio but did not change the total amount of active drug.

Conclusions: We have established a therapeutic range for risperidone. CYP3A4 is a major pathway for risperidone metabolism. Consideration of these factors in clinical practice should lead to improved outcomes for patients treated with risperidone.


High Performance Liquid Chromatography Carbamazepine Clozapine Risperidone Brief Psychiatric Rate Scale 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We express our gratitude to the Janssen Research Foundation for the gift of risperidone and its active metabolite, and for their technical assistance. We thank A. Robinet-Willekens for her help in the translation of the article into English.


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Copyright information

© Adis International Limited 2000

Authors and Affiliations

  • Pascal Odou
    • 1
    • 2
  • J. C. Levron
    • 3
  • M. Luyckx
    • 4
  • C. Brunet
    • 4
  • Hugues Robert
    • 1
    • 2
  1. 1.Service PharmacieEPSM Lille MétropoleArmentièresFrance
  2. 2.Laboratoire de Biopharmacie et Pharmacie Clinique.Faculté des Sciences Pharmaceutiques et BiologiquesLilleFrance
  3. 3.Janssen Research FoundationVal de ReuilFrance
  4. 4.Laboratoire de Pharmacie Clinique, Pharmacocinétique et Pharmacologie.Faculté des Sciences Pharmaceutiques et BiologiquesLilleFrance

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