Impact of treatment duration on mortality among Veterans with opioid use disorder in the United States Veterans Health Administration

Addiction. 2021 Dec;116(12):3494-3503. doi: 10.1111/add.15574. Epub 2021 Jun 1.


Background and aims: While long-term medication-assisted treatment (MAT) using methadone or buprenorphine is associated with significantly lower all-cause mortality for individuals with opioid use disorder (OUD), periods of initiating or discontinuing treatment are associated with higher mortality risks relative to stable treatment. This study aimed to identify the OUD treatment durations necessary for the elevated mortality risks during treatment transitions to be balanced by reductions in mortality while receiving treatment.

Design: Simulation model based on a compartmental model of OUD diagnosis, MAT receipt and all-cause mortality among Veterans with OUD in the United States Veterans Health Administration (VA) in 2017-2018. We simulated methadone and buprenorphine treatments of varying durations using parameters obtained through calibration and published meta-analyses of studies from North America, Europe and Australia.

Setting: United States.

Participants: Simulated cohorts of 10 000 individuals with OUD.

Measurements: All-cause mortality over 12 months.

Findings: Receiving methadone for 4 months or longer or buprenorphine for 2 months or longer resulted in 54 [95% confidence interval (CI) = 5-90] and 65 (95% CI = 21-89) fewer deaths relative to not receiving MAT for the same duration, using VA-specific mortality rates. We estimated shorter treatment durations necessary to achieve net mortality benefits of 2 months or longer for methadone and 1 month or longer for buprenorphine, using non-VA population literature estimates. Sensitivity analyses demonstrated that necessary treatment durations increased more with smaller mortality reductions on treatment than with larger relative risks during treatment transitions.

Conclusions: Short periods (< 6 months) of treatment with either methadone or buprenorphine are likely to yield net mortality benefits for people with opioid use disorder relative to receiving no medications, despite periods of elevated all-cause mortality risk during transitions into and out of treatment. Retaining people with opioid use disorder in treatment longer can increase these benefits.

Keywords: Buprenorphine; Veterans; medications for addiction treatment; methadone; opioid use disorder; simulation modeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics, Opioid / therapeutic use
  • Buprenorphine* / therapeutic use
  • Duration of Therapy
  • Humans
  • Methadone / therapeutic use
  • Opiate Substitution Treatment
  • Opioid-Related Disorders* / drug therapy
  • United States / epidemiology
  • Veterans Health
  • Veterans*


  • Analgesics, Opioid
  • Buprenorphine
  • Methadone