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The association between CYP2D6 genotype and switching antipsychotic medication to clozapine

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Genetic variation in the cytochrome P450 2D6 (CYP2D6) enzyme is responsible for interindividual differences in the metabolism of many antipsychotic drugs, but the clinical relevance of polymorphisms in CYP2D6 for response to antipsychotic treatment is relatively unknown. In the Netherlands, clozapine is prescribed only when patients are non-responsive to or intolerant of at least two different antipsychotics. The aim of our study was to determine the association of the CYP2D6 genotype with switching to clozapine, which served as a surrogate outcome marker for treatment response to antipsychotics.

Methods

CYP2D6 genotype was assessed in patients who had been switched to clozapine and compared with antipsychotic users whose treatment regimen included no more than two different antipsychotic drugs and no clozapine. We also performed the analysis in patients who only used CYP2D6-dependent antipsychotics.

Results

A total of 528 patients were included in the study (222 cases, 306 controls). No statistically significant differences were found in the distribution of the polymorphisms among the case and control groups, both in all patients and in only those patients using CYP2D6-dependent antipsychotics. However, a trend was observed, suggesting an inverse association between CYP2D6 genotype and the switch to clozapine. (9.5 vs. 5.1 % poor metabolisers and 1.3 vs. 2.6 % ultrarapid metabolisers in cases vs. controls, respectively).

Conclusions

Although the results of our study suggest that the CYP2D6 phenotype is not a major determining factor for patients to be switched to clozapine treatment, larger studies are warranted with a focus on the clinical consequences of the CYP2D6 ultrarapid metaboliser and poor metaboliser phenotypes.

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Acknowledgements

The contributions of Dirk van de Glind, John Hinrichs, Rene Herben, Bart Scholten, Annelies Sinke and Marga van Weelden are greatly acknowledged.

Conflict of Interest

None.

Author information

Authors and Affiliations

  1. GGz Centraal Innova, Ermelo, The Netherlands

    Jochem G. Gregoor, Jan van der Weide & Harold J. G. M. van Megen

  2. Department of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

    Jochem G. Gregoor, Antoine C. G. Egberts & Eibert R. Heerdink

  3. Department of Clinical Chemistry, St Jansdal Hospital, PO Box 138, 3840 AC, Harderwijk, The Netherlands

    Karen van der Weide & Jan van der Weide

  4. Department of Clinical Pharmacy, University Medical Centre, Utrecht, The Netherlands

    Antoine C. G. Egberts & Eibert R. Heerdink

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  1. Jochem G. Gregoor
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  2. Karen van der Weide
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  3. Jan van der Weide
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Correspondence to Jan van der Weide.

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Gregoor, J.G., van der Weide, K., van der Weide, J. et al. The association between CYP2D6 genotype and switching antipsychotic medication to clozapine. Eur J Clin Pharmacol 69, 1927–1932 (2013). https://doi.org/10.1007/s00228-013-1553-1

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  • DOI: https://doi.org/10.1007/s00228-013-1553-1

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