The impact of OPRM1's genetic polymorphisms on methadone maintenance treatment in opioid addicts: a systematic review.

Aim: Methadone is a long-acting opioid receptor agonist. It is prescribed to patients with opioid-related use disorders. The OPRM1 gene encodes for methadone's main receptor. It appears that polymorphisms in OPRM1 may affect the efficacy of methadone maintenance treatment (MMT).

Objective: Our purpose was to identify all relevant published papers dealing with the impact ofOPRM1's SNPs  on MMT's efficacy and to summarize results in order to evaluate the relevance of conducting pretherapeutic genotyping in opioid addicts prior to the onset of MMT.

Methods: MEDLINE, PsychINFO and Scopus databases were systematically searched up to 1 January  2018 with no year restrictions using the following keyword combination (MMT) AND (mu or OPRM or mu opioid receptors or SNP or polymorphism or gene). Endpoint of the included studies had to be the impact of OPRM1 gene polymorphisms on the efficacy of MMT and/or methadone required doses during MMT. All abstracts were reviewed to assess papers' relevance. Studies conducted on animals and duplicate papers were excluded.

Results: Our literature search identified 438 articles. Eight of them were included in our systematic review. The total number of included participants was equal to 2170, of whom 1718 underwent MMT. One study reported results of a randomized controlled trial. Three were designed as case-control studies and four as cross-sectional studies. rs1799971 (A118G) was the most studied allele. Results were divergent. Other SNPs might affect MMT's efficacy, however they were scarcely studied.

Conclusion: Genotyping patients with opioid-related use disorders is a promising way to reach a better outcome in patients willing to be on MMT. Focusing on OPRM1 solely should be balanced since polymorphisms in other genes implicated in methadone pharmacodynamics and/or pharmacokinetics may conjunctly affect the efficacy of MMT. Recommendations cannot be enunciated for the moment.