Abnormal movements and tardive dyskinesia in smokers and nonsmokers with schizophrenia genotyped for cytochrome P450 2D6

Study Objective. To investigate the relationships between cytochrome P450 (CYP) 2D6 genotype, antipsychotic drug exposure, abnormal movements and tardive dyskinesia, and cigarette smoking. Design. Prospective, longitudinal study Setting. University mental health research center. Patients. Thirty-seven patients with schizophrenia. Intervention. Patients were genotyped for CYP2D6*1, *3, and *4 alleles, and data were collected on their psychiatric symptoms, cigarette smoking status, and antipsychotic drug exposure. Abnormal movements were measured using the Abnormal Involuntary Movement Scale (AIMS). Presence of tardive dyskinesia was also evaluated. Measurements and Main Results. A linear regression model used the AIMS scores as the dependent variable, and genotype, sex, smoking status, and antipsychotic drug exposure as independent variables. Antipsychotic drug exposure, genotype, and cigarette smoking interaction was significant (p<0.0212) for patients with the CYP2D6*1/*3, *4 genotype. Seventy-eight percent of smokers with the CYP2D6*1/*3, *4 genotype had tardive dyskinesia compared with 20-33% of patients in other groups. Conclusion. Patients with a CYP2D6*3 or *4 allele may shunt antipsychotic metabolism through other pathways that are induced by cigarette smoke. This induction may result in formation of neurotoxic metabolites, leading to increased AIMS scores and a higher frequency of tardive dyskinesia compared with patients without these alleles.