Death risk among opioid overdose survivors lower with methadone vs buprenorphine-naloxone

Among survivors of an opioid overdose, treatment initiation with methadone is associated with a reduced risk of death compared with buprenorphine-naloxone, according to a retrospective study.

Researchers emulated a target trial using a retrospective cohort of individuals who started treatment with methadone or buprenorphine-naloxone in Ontario, Canada. All participants had a history of emergency department visit for an opioid overdose in the past year and had no previous exposure to either methadone or buprenorphine-naloxone. Participants starting each medication were matched based on propensity scores, sex, and index date.

The primary outcome was death from any cause within 1 year. Secondary outcomes included opioid overdose and treatment discontinuation.

The analysis included a total of 5,882 participants (mean age 35.8 years, 32.1 percent female), with 2,941 each in the methadone and buprenorphine-naloxone groups.

Within 1 year, 5.6 percent of participants in the methadone group and 7.1 percent in the buprenorphine-naloxone–initiating group died (hazard ratio [HR], 0.78, 95 percent confidence interval [CI], 0.63–0.95; p=0.01).

Median time to treatment discontinuation was 25 days in the methadone group vs 16 days (in the buprenorphine-naloxone group (HR, 0.78, 95 percent CI, 0.74–0.82; p<0.001). Time to first opioid overdose was similar between the two groups (HR, 1.07, 95 percent CI, 0.97–1.18; p=0.17).

In the per-protocol analyses, the risk of death did not significantly differ between the methadone and buprenorphine-naloxone groups (HR, 0.84, 95 percent CI, 0.48–1.47; p=0.55), but the risk of opioid overdose was higher in the methadone group (HR, 1.52, 95 percent CI, 1.19–1.93; p<0.001).

More studies are needed to confirm the findings.