Cyp2d6*3, *4, *5 and *6 polymorphisms and antipsychotic-induced extrapyramidal side-effects in patients receiving antipsychotic therapy.

1. The aim of the present study was to examine the relationship between CYP2D6 polymorphisms and the risk of antipsychotic (AP)-induced extrapyramidal symptoms (EPS) in patients receiving AP treatment. The allele status for CYP2D6*3, CYP2D6*4, CYP2D6*5 and CYP2D6*6 was determined in 267 patients receiving AP therapy. Seventy-nine cases presenting with EPS (Simpson-Angus Scale 3) and 188 controls without EPS (Simpson-Angus > 3) took part in the study. 2. We found a non-significant over-representation of poor metaboliser genotypes among cases, but a significant association between the mutant homozygous genotype for CYP2D6*4 (odds ratio (OR) 4.1, 95% confidence interval (CI) 1.01-16, permutated P value 0.01) and the heterozygous genotype for CYP2D6*6 (OR 5.4, 95% CI 1.13-18, permutated P value 0.003) and the risk of suffering EPS. 3. These results suggest that the CYP2D6 genotype may be a contributory factor in the development of EPS in patients undergoing AP therapy.