Pharmacopsychiatry 2003; 36(2): 73-78
DOI: 10.1055/s-2003-39048
Original Paper
© Georg Thieme Verlag Stuttgart · New York

CYP2D6 Polymorphism and Tardive Dyskinesia in Schizophrenic Patients

P. L. Lohmann1 , M. Bagli1 , H. Krauss4 , D. J. Müller1 , T. G. Schulze1 , H. Fangerau1 , M. Ludwig2 , K. Barkow1 , T. Held3 , R. Heun1 , W. Maier1 , M. Rietschel1 , M. L. Rao1
  • 1Department of Psychiatry, University of Bonn, Germany
  • 2Institute of Clinical Biochemistry, University of Bonn, Germany
  • 3Mental State Hospital, Rheinische Kliniken, Bonn, Germany
  • 4Psychiatric Department of the Christian General Hospital Quakenbrück, Germany
Further Information

Publication History

Received: 3.7.2001 Revised: 26.6.2002

Accepted: 15.7.2002

Publication Date:
06 May 2003 (online)

Antipsychotic drug-induced tardive dyskinesia (TD) is a serious problem during psychopharmacologic treatment of schizophrenic patients. In search of genetic factors contributing to TD, there is a lack of consensus regarding the role of the polymorphic isozyme cytochrome P450 CYP2D6, which is involved in the oxidative metabolism of antipsychotic drugs. In the present case-control study, we tested the putative influence of the CYP2D6 genotype on the development of TD. Out of 157 patients, 109 were retrospectively selected meeting DSM IV criteria for schizophrenia or schizoaffective disorder, and 50 of them persistently presenting with TD. Genotyping detected the functional allele CYP2D6 *1, the known major defective alleles CYP2D6 *3, *4, *5, *6, and gene duplication. According to their number of functional CYP2D6 alleles, subjects were divided into carriers of none, one, or at least two functional CYP2D6 alleles. The proportions of these categories did not differ between patients and an ethnically homogenous control population (n = 195, p = 0.99) or between patients with and without TD (p = 0.818). Schizophrenic patients were carriers of gene duplication more often than healthy probands, without revealing statistical significance (p = 0.10). Out of seven patients with gene duplication, three developed persistent TD. Furthermore, patients with and without TD were comparable according to age, age of onset, gender, and duration of illness, but subjects with TD had taken more lifetime chlorpromazine equivalents (CPZ) than had patients without TD (χ2-test, Student’s t-test). Forward as well as backward logistic regression analyses confirmed that the presence of TD was influenced by lifetime CPZ but not by age, age of onset, gender, duration of illness, or CYP2D6 genotype. In contrast to the relevance of lifetime CPZ, the lifetime dose of antipsychotic drugs known to be metabolized by CYP2D6 did not significantly influence the presence of TD. In conclusion, our results provide no evidence for the contribution of CYP2D6 genotype to the development of TD in schizophrenic patients receiving long-term antipsychotic medication.

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Prof. Dr. Marie Luise Rao

Department of Psychiatry and Psychotherapy

University of Bonn

Sigmund-Freud-Str. 25

53105 Bonn

Germany

Phone: +49 228/287-6125

Fax: +49 228/287-6383

Email: m.l.rao@uni-bonn.de

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