Aim: Clinical trials with healthy volunteers are a useful model for evaluating safety and tolerability, without the interference of concomitant diseases and drugs. The present study aims to improve our understanding of antipsychotic-related adverse reactions (ARs) and their possible association with common genetic variants of pharmacodynamic proteins such as neurotransmitter receptors/transporters.
Materials & methods: A total of eight polymorphisms located in seven pharmacodynamic-related genes (SCL6A4, MDR1, 5HT2A, DRD2, DRD3, COMT and GRIN2B) were genotyped in a cohort of 211 healthy volunteers who received a single dose of risperidone (1 mg), olanzapine (5 mg) or quetiapine (25 mg).
Results: Interestingly, a significant association was found between the incidence of neurological ARs and specific polymorphisms in key genes (DRD2 and SCL6A4).
Conclusion: Genetic variants in pharmacodynamic genes could represent valuable markers of AR risk and antipsychotic safety. Original submitted 7 February 2013; Revision submitted 3 June 2013.