Pharmacogenetic studies of drug response in schizophrenia

Abstract

Treatment with antipsychotics is marred by frequent failure and adverse reactions. About a third of treated patients will not improve adequately, and more than 60% will develop severe and long-lasting side-effects, including weight gain (developed by 10-57% of treated patients) and tardive dyskinesia (4-65%) among others. Genetic, clinical and environmental factors contribute to the variability observed in response to antipsychotic treatment. Genetic research has identified several polymorphisms in pharmacokinetic and pharmacodynamic genes contributing to response variability. In particular, functional polymorphisms in genes coding for cytochrome P450 (CYP) enzymes have been demonstrated to influence antipsychotic biotransformation rates and response variability, whereas genes coding for drug targets have been suggested to influence the level of efficacy of antipsychotics. Characterization of key pharmacogenetic genes before the start or change of antipsychotic treatment may help to improve the efficacy and safety of pharmacological treatments. Although evaluation studies are still sparse, there is growing evidence of the clinical and economic benefits of introducing pharmacogenetic information as a prescription aid in clinical settings.