Title:Pharmacogenetics in Methadone Therapy
VOLUME: 12 ISSUE: 4
Author(s):Eugene Lin and Shih-Jen Tsai
Affiliation:Vita Genomics, Inc., 7 Fl., No. 6, Sec. 1, Jung-Shing Road, Wugu Shiang, Taipei, Taiwan.
Keywords:Association study, methadone, personalized medicine, pharmacogenetics, single nucleotide polymorphisms.
Abstract: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.
