Pharmacogenetics in Methadone Therapy

Methadone, a synthetic opioid, is mainly used as an analgesic and a maintenance antiaddictive and reductive preparation in the treatment of opioid dependence. A better understanding of the factors underlying individual responses to methadone is required in order to improve treatment individualization, thereby potentially leading to better clinical efficacy. Evidence now suggests that pharmacogenetics has a role in the effects of methadone medications, and the efficacy of methadone results from the combined effects of a number of genetic variants, such as single nucleotide polymorphisms (SNPs). Although there are not enough data currently available to prove this hypothesis, more and more genetic variants associated with methadone response are being discovered. In this review, we focus on the most recent developments in pharmacogenetics of methadone. Firstly, we survey the SNPs and genes identified as genetic markers that are correlated and associated with methadone treatment responses in various association studies. Secondly, we investigate candidate genes that have been suggested as contributing to pharmacokinetic properties during the course of methadone treatment in the various studies. For example, cytochrome P450 (CYP) 3A4 and 2B6 have been identified as the main candidate genes involved in methadone metabolism. Furthermore, we summarize the limitations with respect to the mentioned pharmacogenetics studies. Finally, we address a discussion of future directions and challenges. Future research with independent replication in light of large sample sizes and gene-gene interactions is needed to confirm the role of the candidate genes identified in these studies in methadone treatment response and will probably have major contributions for personalized medicine.