Opioid Agonist Treatment Linked to Lower Rate of Mortality, Despite Limited Access


Potential public health benefit of OAT linked to 50% lower risk of all-cause mortality.

Thomas Santo Jr, MPH

Thomas Santo Jr, MPH

As the opioid crisis has led to increases in opioid overdose, particularly during the COVID-19 pandemic, opioid agonist treatment (OAT) is an effective option for patients with opioid dependence.

However, a lack of systematic review on OAT and specific causes of mortality led a new study to determine the relationship between OAT and mortality rates.

The team, led by Thomas Santo Jr, MPH, National Drug and Alcohol Research Centre found an association with OAT and lower rate of mortality, but access to OAT and insurance coverage of treatment remains limited.


A systematic review of 3 peer-reviewed databases (Medline, Embase, and PsycINFO) took place from January – February 2020.

The team examined all-cause and cause-specific crude mortality rates (CMRs) during and out of OAT, for randomized clinical trials (RCTs) and observational studies.

They noted the study followed the Preferred Reporting Items for Systemic Reviews and Meta-analyses (PRISMA) guidelines.

Santo and colleagues collected data on participant and study characteristics, including treatment modality characteristics, number of deaths, person-years at risk, and all-cause and cause-specific mortality.

They also calculated log-transformed rate ratios (RRs) in comparison of binary death and participant totals in RCTs.

In addition, they calculated crude mortality rates (CMR) to divide observed number of deaths by person-years.

Main outcomes for the study included overall all-cause and cause-specific mortality by setting and participant characteristics. They noted that methadone and buprenorphine OAT had specific evaluations.


While 7980 studies were identified, only 72 met inclusion criteria. The team included 15 RCTs with 3852 participants and 36 primary cohort studies with 749,634 participants analyzed.

The team found 45 deaths reported across RCTs, with 7 of 15 RCTs reporting 0 deaths.

Further, no significant difference was found in all-cause mortality for patients allocated to OAT compared to comparison groups (RR, 0.86; 95% CI, 0.59 – 1.23).

Data show the rate of all-cause mortality during OAT was more than half of the rate seen during time out of OAT (RR 0.47; 95% CI, 0.42 – 0.53).

The team observed associations were not different for methadone (RR 0.47; 95% CI, 0.41 – 0.54) compared to buprenorphine (RR 0.34; 95% CI, 0.26 – 0.45).

During OAT, data show a lower risk of suicide (RR 0.48; 95% CI, 0.37 – 0.61), cancer (RR 0.72; 95% CI, 0.52 – 0.98)

Consequently, the data show a lower risk of drug-related mortality (RR 0.41; 95% CI, 0.33 – 0.52), alcohol-related mortality (RR 0.59; 95% CI, 0.49 – 0.72), and cardiovascular-related mortality (RR 0.41; 95% CI, 0.33 – 0.52).

The numbers show that rates of all-cause mortality and drug-related poisoning were nearly double the rates during OAT (RR 2.01; 95% CI. 1.55 – 5.09), but not in buprenorphine (RR 0.58; 95% CI, 0.18 – 1.85).

As such, all-cause mortality was 6 times higher in 4 weeks after OAT cessation (RR 6.01; 95% CI, 4.32 – 8.36). The remainder of time not receiving OAT remained double the rate (RR 1.81; 95% CI, 1.50 – 2.18).


The results of the analysis suggest a potential public health benefit of OAT, with a 50% lower risk of all-cause mortality, drug-related deaths, and suicide, across a large range of characteristics.

However, the team noted that access to OAT is limited, which might be critical to reduce rates of mortality among patients with opioid dependence.

“Despite this positive association, access to OAT remains limited in many settings, and in the US and globally, coverage for this type of treatment is low,” investigators wrote. “Future work to increase access could have important population-level benefits.”

The study, “Association of Opioid Agonist Treatment with All-Cause Mortality and Specific Causes of Death Among People with Opioid Dependence,” was published online in JAMA Psychiatry.

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