Risk of Mortality on and Off Methadone Substitution Treatment in Primary Care: A National Cohort Study

Addiction. 2016 Jan;111(1):73-82. doi: 10.1111/add.13087. Epub 2015 Sep 28.


Aim: To assess whether risk of death increases during periods of treatment transition, and investigate the impact of supervised methadone consumption on drug-related and all-cause mortality.

Design: National Irish cohort study.

Setting: Primary care.

Participants: A total of 6983 patients on a national methadone treatment register aged 16-65 years between 2004 and 2010.

Measurement: Drug-related (primary outcome) and all-cause (secondary outcome) mortality rates and rate ratios for periods on and off treatment; and the impact of regular supervised methadone consumption.

Results: Crude drug-related mortality rates were 0.24 per 100 person-years on treatment and 0.39 off treatment, adjusted mortality rate ratio 1.63 [95% confidence interval (CI) = 0.66-4.00]. Crude all-cause mortality rate per 100 person-years was 0.51 on treatment versus 1.57 off treatment, adjusted mortality rate ratio 3.64 (95% CI = 2.11-6.30). All-cause mortality off treatment was 6.36 (95% CI = 2.84-14.22) times higher in the first 2 weeks, 9.12 (95% CI = 3.17-26.28) times higher in weeks 3-4, compared with being 5 weeks or more in treatment. All-cause mortality was lower in those with regular supervision (crude mortality rate 0.60 versus 0.81 per 100 person-years) although, after adjustment, insufficient evidence exists to suggest that regular supervision is protective (mortality rate ratio = 1.23, 95% CI = 0.67-2.27).

Conclusions: Among primary care patients undergoing methadone treatment, continuing in methadone treatment is associated with a reduced risk of death. Patients' risk of all-cause mortality increases following treatment cessation, and is highest in the initial 4-week period.

Keywords: All-cause mortality; cohort study; drug-related deaths; maintenance treatment; methadone; mortality; opioid; supervised consumption.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cohort Studies
  • Female
  • Humans
  • Ireland / epidemiology
  • Male
  • Methadone / therapeutic use*
  • Middle Aged
  • Opiate Substitution Treatment / methods
  • Opiate Substitution Treatment / mortality*
  • Opioid-Related Disorders / drug therapy*
  • Opioid-Related Disorders / mortality*
  • Primary Health Care / methods*
  • Risk Assessment / statistics & numerical data
  • Young Adult


  • Methadone