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Increased incidence of CYP2D6 gene duplication in patients with persistent mood disorders: ultrarapid metabolism of antidepressants as a cause of nonresponse. A pilot study

  • Pharmacogenetics
  • Published:
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Abstract

Objective

Recent studies have revealed that genetic polymorphisms of cytochrome P 450 2D6 (CYP2D6) are among the factors that determine the interindividual differences in the metabolism and response to antidepressants. We investigated the relationship between persistent mood disorders and the duplication of the CYP2D6 gene, which encodes an enzyme with increased activity.

Methods

We screened the prevalence of the CYP2D6 genotypes in 108 patients with persistent mood disorders using long polymerase chain reaction (PCR) and the real-time PCR methods. Clinical correlates with the genotypes were also analyzed.

Results

Among the 108 patients, 81 had failed to respond to antidepressants shown to be metabolized by CYP2D6. Of those 81, 8 had a CYP2D6 gene duplication (9.9%, 95% confidence interval 3.4–16.4%) which was higher than the 0.8–1.0% incidence previously observed in healthy Nordic Caucasians. The worst week scores of the Hamilton Depression Rating Scale were higher in the patients with the duplication compared with those without the duplication (P=0.026, student’s t-test).

Conclusion

These results suggest that the CYP2D6 gene duplication is a possible factor that influences the development of persistence in patients with mood disorders probably by ultrarapid drug metabolism.

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Acknowledgements

We thank Lilleba Bohman, and Ulla Petterson for technical supports in the genetic studies. This study was supported by Eli Lilly Fellowship for Clinical Psychopharmacology.

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Authors and Affiliations

  1. Department of Medical Laboratory Sciences and Technology, Division of Clinical Pharmacology, Karolinska Institutet, Huddinge University Hospital, 14186, Stockholm, Sweden

    Chiaki Kawanishi

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

    Chiaki Kawanishi

  3. Department of Medical Laboratory Sciences and Technology, Division of Clinical Pharmacology, Karolinska Institutet, Huddinge University Hospital, 14186, Stockholm, Sweden

    Stefan Lundgren & Leif Bertilsson

  4. Department of Psychiatry, Karolinska Institutet, Huddinge University Hospital, 14186, Stockholm, Sweden

    Hans Ågren

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  1. Chiaki Kawanishi
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  2. Stefan Lundgren
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  4. Leif Bertilsson
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Correspondence to Chiaki Kawanishi.

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Kawanishi, C., Lundgren, S., Ågren, H. et al. Increased incidence of CYP2D6 gene duplication in patients with persistent mood disorders: ultrarapid metabolism of antidepressants as a cause of nonresponse. A pilot study. Eur J Clin Pharmacol 59, 803–807 (2004). https://doi.org/10.1007/s00228-003-0701-4

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  • DOI: https://doi.org/10.1007/s00228-003-0701-4

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