Clinical significance of pharmacogenomic studies in tardive dyskinesia associated with patients with psychiatric disorders

Abstract

Florence CF Chang, Victor SC Fung Movement Disorders Unit, Department of Neurology, Westmead Hospital, Sydney Medical School, University of Sydney, Sydney, NSW, Australia Abstract: Pharmacogenomics is the study of the effects of genetic polymorphisms on medication pharmacokinetics and pharmacodynamics. It offers advantages in predicting drug efficacy and/or toxicity and has already changed clinical practice in many fields of medicine. Tardive dyskinesia (TD) is a movement disorder that rarely remits and poses significant social stigma and physical discomfort for the patient. Pharmacokinetic studies show an association between cytochrome P450 enzyme-determined poor metabolizer status and elevated serum antipsychotic and metabolite levels. However, few prospective studies have shown this to correlate with the occurrence of TD. Many retrospective, case-control and cross-sectional studies have examined the association of cytochrome P450 enzyme, dopamine (receptor, metabolizer and transporter), serotonin (receptor and transporter), and oxidative stress enzyme gene polymorphisms with the occurrence and severity of TD. These studies have produced conflicting and confusing results secondary to heterogeneous inclusion criteria and other patient characteristics that also act as confounding factors. This paper aims to review and summarize the pharmacogenetic findings in antipsychotic-associated TD and assess its clinical significance for psychiatry patients. In addition, we hope to provide insight into areas that need further research. Keywords: pharmacogenomics, tardive dyskinesia, cytochrome P450, pharmacogenetic, schizophrenia