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Related Experiment Videos

Drug extrapyramidal side-effects or not: is there a dextromethorphan phenotype difference?

P Vandel1, E Haffen, S Vandel

  • 1Service de Psychiatrie, Centre Hospitalo-Universitaire, Besançon, France.

Therapie
|September 1, 2000
PubMed
Summary

Genetic variations in cytochrome P450 2D6 (CYP2D6) metabolism may increase the risk of psychotropic drug-induced extrapyramidal side-effects. Poor CYP2D6 metabolizers showed a higher incidence of these adverse drug reactions.

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Area of Science:

  • Pharmacogenetics
  • Neuropharmacology

Background:

  • Cytochrome P450 2D6 (CYP2D6) metabolizes numerous psychotropic medications.
  • Polymorphisms in CYP2D6 are linked to altered drug metabolism and potential adverse effects.
  • Extrapyramidal side-effects (EPS) are common adverse reactions to antipsychotic and antidepressant drugs.

Purpose of the Study:

  • To investigate the association between CYP2D6 metabolizer phenotype and the occurrence of EPS in psychiatric patients.
  • To determine if CYP2D6 poor metabolizer status is a risk factor for developing EPS.

Main Methods:

  • Compared CYP2D6 metabolizer phenotype using a dextromethorphan test in two groups of adult psychiatric patients.
  • Group 1: 31 patients with drug-induced EPS. Group 2: 31 matched patients without EPS.
  • Defined poor metabolizers by a dextromethorphan metabolic ratio > 0.3.

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Main Results:

  • 13 out of 31 patients (41.9%) in Group 1 were identified as poor CYP2D6 metabolizers.
  • Only 2 out of 31 patients (6.4%) in Group 2 were poor CYP2D6 metabolizers.
  • A significantly higher prevalence of poor metabolizers was observed in patients experiencing EPS.

Conclusions:

  • CYP2D6 poor metabolizer status may be a risk factor for developing drug-induced extrapyramidal side-effects.
  • In patients with likely saturated CYP2D6 activity, the risk of EPS might be elevated.
  • Consideration of psychotropic drugs with lower EPS risk is recommended for patients with impaired CYP2D6 metabolism.