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Effects of CYP2D6 polymorphisms on neuroleptic malignant syndrome

Daiji Kato1, Chiaki Kawanishi, Ikuko Kishida

  • 1Department of Psychiatry, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan.

European Journal of Clinical Pharmacology
|August 19, 2007
PubMed
Abstract

Insights

The CYP2D6*5 allele may increase the risk of developing neuroleptic malignant syndrome (NMS), a severe antipsychotic drug reaction. This genetic variation was more common in NMS patients who took CYP2D6 substrates.

Area of Science:

  • Pharmacogenetics
  • Neuroscience
  • Clinical Pharmacology

Background:

  • Neuroleptic malignant syndrome (NMS) is a critical adverse drug reaction associated with antipsychotic medications.
  • Genetic factors, particularly drug metabolism gene polymorphisms, are increasingly recognized as influencing NMS susceptibility.

Purpose of the Study:

  • To investigate the association between CYP2D6 gene polymorphisms and the occurrence of NMS in a Japanese population.
  • To determine if specific CYP2D6 genotypes increase the risk of developing NMS.

Main Methods:

  • A case-control study involving 53 NMS patients and 112 healthy controls.
  • Genotyping of CYP2D6 alleles (*5, *10, *4, duplicated) using polymerase chain reaction and restriction fragment length polymorphism analysis.
  • Retrospective identification of NMS-causing drugs and analysis of CYP2D6 substrate use.

Main Results:

  • The prevalence of the CYP2D6*5 allele was higher in NMS patients compared to controls, although not statistically significant overall (10.4% vs. 5.4%).
  • A statistically significant association was found between the CYP2D6*5 allele and NMS in patients who had taken CYP2D6 substrates (15.5% vs. 5.4%, P = 0.020).
  • No significant association was observed for the CYP2D6*10 allele.

Conclusions:

  • The CYP2D6*5 allele may confer increased vulnerability to developing neuroleptic malignant syndrome.
  • CYP2D6 genetic variations are important factors to consider in the risk assessment for NMS in patients treated with antipsychotics.

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