Genetic association between the DRD4 promoter polymorphism and clozapine-induced sialorrhea.

The use of clozapine, an effective antipsychotic drug used in treatment-resistant schizophrenia, is associated with adverse effects. Sialorrhea is one such effect, which can be distressing for many patients. Studies on the pharmacogenetics of the adverse effects of clozapine are limited. The aim of the present study was to determine whether clozapine-induced sialorrhea is associated with a 120 base-pairs (bp) tandem duplication polymorphism in the dopamine receptor subtype D4 (DRD4) gene. Ninety-five patients, mean age 35.43±9.43 years, with treatment-resistant schizophrenia and on clozapine were included in the study. Development of sialorrhea in response to the drug, as manifested by drooling of saliva, was documented in 45 (47.4%) patients. Genotyping of the patients was carried out to detect the presence of the polymorphism of interest. Clozapine-induced sialorrhea was found to be associated significantly with the 120-bp duplication in DRD4. The association was found to fit a log-additive model with an odds ratio of 2.95 (95% confidence interval 1.51-5.75; P=0.0006). Thus, the presence of the 120-bp duplication in DRD4 appears to confer a risk for sialorrhea in response to clozapine therapy. The underlying pathophysiology and clinical significance of this phenomenon warrant further investigation.