Pharmacogenetic Studies Investigating the Adverse Effects of Antipsychotics

Review Article

Psychiatry Investigation 2007;4(2):66-75.

Heon-Jeong Lee, MD, PhD

Department of Psychiatry, Division of Brain Korea ²¹ for Biomedical Science, Korea University College of Medicine, Seoul, Korea

Abstract

<p class="MsoPlainText" style="word-spacing: 1; line-height: 150%; margin-top: 0; margin-bottom: 0" align="left"><font face="HY중고딕" size="2">The pharmacogenetic study of antipsychotics has been developed along with the development of general techniques of genetic analysis. Because there are no significant differences in the clinical efficacy of the various antipsychotics, it is important to prevent the adverse effects of antipsychotics. Therefore, pharmacogenetic studies concerning antipsychotics have been primarily focused on their adverse effects. The most significant finding of the previous studies is the association between drug effects and drug metabolic polymorphisms, mainly in the cytochrome P450 (CYP) genes. Patients with genetically determined to be CYP poor metabolizers (PMs) may require lower doses of antipsychotic medications. On the other hand, CYP ultrarapid matabolizers (UMs) will need an increased dosage in order to obtain a therapeutic response. Genetic variations in the dopamine and serotonin receptor genes have been reported to be associated with the adverse effects of antipsychotics, reflecting the affinities that most antipsychotics have for these receptors. In particular, there is evidence to suggest an association between dopamine 2 receptor polymorphisms and a dopamine 3 receptor polymorphism and antipsychotic-induced tardive dyskinesia. Several studies were recently performed to determine the genetic susceptibility to antipsychotic-induced weight gain and metabolic syndrome. Adrenergic 2a receptor, leptin gene, and serotonin 2C receptor gene variants have been reported to be associated with drug-induced weight gain. Genetic tests before treatment will provide the necessary information on the patient's metabolic status, which will aid in the appropriate adjustment of the therapeutic doses and the reduction of adverse reactions. Pharmacogenetic knowledge has obvious implications for the selection and improvement of antipsychotic treatment. These developments can be considered to be successes, but the objectives of bringing pharmacogenetic and pharmacogenomic research into psychiatric clinical practice are far from being realized. This review summarizes the findings of the previous research in the field. The current knowledge on the genetic prediction of drug metabolic status and drug-induced side effects will be reviewed and discussed.

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Key words Pharmacogenetics;Antipsychotics;Adverse effects;Tardive dyskinesia;Weight gain.