According to a systematic review and meta-analysis, opioid agonist treatment (OAT) for individuals with opioid dependence was found to decrease mortality risk, according to findings published in JAMA Psychiatry.

Publication databases were searched through February 2020 for studies of OAT and mortality. A total of 15 randomized clinical trials comprising 3852 individuals and 36 primary cohort studies comprising 749,634 individuals met inclusion criteria.

Among the trials, buprenorphine was the most common OAT (47%), and the studies most frequently used detoxification as the primary comparator. More than half (53%) of the studies reported losing more than 20% of participants during follow-up (£6 months).

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A total of 45 deaths were reported during the trials. The studies did not report a significant difference in all-cause mortality risk among patients allocated OAT (rate ratio [RR], 0.86; 95% CI, 0.59-1.23).

For the observational studies, methadone was the most common OAT (78%). Nearly half of the studies (44%) analyzed registry data.

The crude mortality rate was 11 deaths per 1000 person-years among individuals receiving OAT compared with 23.97 deaths per 1000 person-years among those not receiving OAT. These values equated to a more than 50% reduction in mortality for individuals using OAT (RR, 0.47; 95% CI, 0.42-0.53). The decreased mortality risk did not differ significantly for methadone (RR, 0.47; 95% CI, 0.41-0.54) or buprenorphine (RR, 0.34; 95% CI, 0.26-0.45).

In addition, OAT was found to be associated with decreased risk for injury and poisoning (pooled RR, 0.34; 95% CI, 0.27-0.42), unintentional drug-related death (pooled RR, 0.41; 95% CI, 0.33-0.52), suicide (pooled RR, 0.48; 95% CI, 0.37-0.61), alcohol-related mortality (pooled RR, 0.59; 95% CI, 0.49-0.72), cardiovascular-related mortality (pooled RR, 0.69; 95% CI,0.60-0.79), and cancer (pooled RR, 0.72; 95% CI, 0.54-0.98).

During the OAT course, mortality was highest during the first 4 weeks of treatment (RR, 1.92; 95% CI, 1.10-3.35) and during the first 4 weeks after OAT cessation (RR, 6.01; 95% CI, 4.32-8.36).

Risk for bias was high for 80% of the randomized clinical trials due to missing data.

This analysis was limited by the large amount of missing or ambiguous information such as intervention delivery, patient characteristics, or reason for participant loss during follow-up.

These data suggested that OAT significantly decreases risk for mortality and adverse effects. The study authors asserted that despite the positive relationship between OAT and outcomes, access to OAT and insurance coverage remains low worldwide. Additional research is needed to assess effective strategies for increasing access for individuals in need.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Santo T, Clark B, Hickman M, et al. Association of opioid agonist treatment with all-cause mortality and specific causes of death among people with opioid dependence: a systematic review and meta-analysis. JAMA Psychiatry. Published online June 2, 2021. doi:10.1001/jamapsychiatry.2021.0976

This article originally appeared on Psychiatry Advisor