Opioid agonist treatment 'important intervention' for those with opioid dependence

Opioid agonist treatment reduced mortality rates among people with opioid dependence, according to results of a systematic review and meta-analysis published in JAMA Psychiatry.

“There is robust evidence from a recent systematic review that during [opioid agonist treatment], overdose and all-cause mortality are reduced among people with opioid dependence,” Thomas Santo Jr., MPH, of the National Drug and Alcohol Research Centre in Australia, and colleagues wrote. “That review also found that people who cease [opioid agonist treatment] are at the highest risk of all-cause and overdose mortality in the first 4 weeks after treatment cessation and that risk [for] mortality is elevated in the first 4 weeks of [opioid agonist treatment] compared with the remainder of time receiving [opioid agonist treatment]. To our knowledge, there has not been a systematic examination of (1) the evidence on the potential association of [opioid agonist treatment] with other causes of death or (2) [opioid agonist treatment] provided in alternative settings, including during and immediately after incarceration.”

The researchers aimed to evaluate the effects of time receiving opioid agonist treatment on mortality by searching three databases through Feb. 18, 2020, including clinical trial registries and previous Cochrane reviews in the current study. Specifically, they included all observational studies with data on all-cause or cause-specific mortality among people with opioid dependence while receiving and not receiving opioid agonist treatment. They also included randomized clinical trials.

Santo and colleagues extracted data on study, participant and treatment characteristics and calculated person-years, all-cause mortality and cause-specific mortality. They used random-effects meta-analyses to pool crude mortality rates and rate ratios.

The analysis included 15 randomized clinical trials with 3,852 total participants and 36 primary cohort studies with 749,634 total participants. Results showed the rate of all-cause mortality during opioid agonist treatment was more than half of the rate observed during time out of opioid agonist treatment (RR = 0.47; 95% CI, 0.42-0.53) among the cohort studies. After controlling for patient sex, age, geographic location, HIV status and hepatitis C virus status and whether drugs were taken via injection, the researchers noted that this association remained consistent. They did not observe a difference in association for methadone (RR = 0.47; 95% CI, 0.41-0.54) compared with buprenorphine (RR = 0.34; 95% CI, 0.26-0.45). During opioid agonist treatment, risk appeared lower for suicide (RR = 0.48; 95% CI, 0.37-0.61), cancer (RR = 0.72; 95% CI, 0.52-0.98), drug-related (RR = 0.41; 95% CI, 0.33-0.52), alcohol-related (RR = 0.59; 95% CI, 0.49-0.72) and cardiovascular-related (RR = 0.69; 95% CI, 0.60-0.79) mortality. All-cause mortality and drug-related poisoning rates in the first 4 weeks of methadone treatment were nearly twice the rates during the remainder of opioid agonist treatment (RR = 2.01; 95% CI, 1.55-5.09) but not for buprenorphine (RR = 0.58; 95% CI, 0.18-1.85). In the 4 weeks following cessation of opioid agonist treatment (RR = 6.01; 95% CI, 4.32-8.36), all-cause mortality was six times higher and remained double the rate for the remainder of time not receiving opioid agonist treatment (RR = 1.81; 95% CI, 1.5-2.18). The researchers noted an association between opioid agonist treatment and lower risk for mortality during incarceration (RR = 0.06; 95% CI, 0.01-0.46) and following release from incarceration (RR = 0.09; 95% CI, 0.02-0.56).

“The results of this systematic review meta-analysis suggest that [opioid agonist treatment] is an important intervention for people with opioid dependence, with the capacity to reduce multiple causes of death,” Santo and colleagues wrote. “Despite this positive association, access to [opioid agonist treatment] remains limited in many settings, and in the U.S. and globally, coverage for this type of treatment is low. Future work to increase access could have important population-level benefits.”