Genetic influence on methadone treatment outcomes in patients undergoing methadone maintenance treatment for opioid addiction: a pilot study

Abstract

Introduction

Treatment of opioid addiction with methadone is effective; however, it is known to produce interindividual variability. This may be influenced in part by genetic variants, which can increase the initial risk of developing opioid addiction as well as explain differences in response to treatment. This pilot study aimed to assess the feasibility of conducting a full-scale genetic analysis to identify genes that predict methadone treatment outcomes in this population.

Methods

This was a cross-sectional observational study of patients admitted to a methadone maintenance treatment program for opioid addiction. We obtained demographic and clinical characteristics in addition to blood and urine samples, for the assessment of treatment outcomes.

Results

The recruitment process yielded 252 patients, representing a 20% recruitment rate. We conducted genetic testing based on a 99.6% rate of provision of DNA samples. The average retention in treatment was 3.4 years, and >50% of the participants reported psychiatric and medical comorbidities. BDNF rs6265 and DRD2 rs1799978 were the common single nucleotide polymorphisms (SNPs) selected for the feasibility study.

Discussion

This study met our predetermined feasibility criteria; recruitment, response rates, and genetic testing were feasible; treatment duration was sufficient for follow up; and the prevalence of comorbid conditions indicated the need for reliable psychiatric and chronic pain measures. The study strengths included effective collaboration with clinics and the generalizability of sample population. Key learning points show the need for assessment of treatment outcomes on multiple domains, implementation of follow up, and the development of standardized training for the study clinical staff.

Keywords:

• genetics
• substitute opioid therapy
• treatment response
• risk factors

Acknowledgments

We would like to sincerely thank and recognize everyone who contributed to the completion of this investigation. We thank all members of the OATC clinical staff for their great efforts in recruitment and data collection, with a special thanks going out to the recruiting nurses (D Tirabassi, T Dillon, C Geroux, B Heipel, S Rutherford, and H Cotterill). In addition, we would like to express gratitude to the McMaster University undergraduate students who volunteered a great deal of time to help with data entry and cleaning, as well as genetic analysis. These students include Sindoora Iyre, Sohail Mahmood, Leen Naji, Anuja Bhalerao, Herman Bami, and Andrew Kamphuis. We also thank all patients from the Ontario Addiction Treatment Centres (OATC) methadone treatment facilities who participated and generously donated their time, information, and samples; without them this study would not be possible. This work was supported by a Canadian Institutes of Health Research (CIHR) Drug Safety and Effectiveness Network (DSEN) grant (grant number: 126639). This work was also supported by an Innovation Award from the Department of Psychiatry and Behavioural Neurosciences, McMaster University (grant number: 2-15311).

Disclosure

The authors report no conflicts of interest in this work.