Association of Opioid Agonist Treatment With All-Cause Mortality and Specific Causes of Death Among People With Opioid Dependence

Abstract

IMPORTANCE Mortality among people with opioid dependence is higher than that of the general population. Opioid agonist treatment (OAT) is an effective treatment for opioid dependence; however, there has not yet been a systematic review on the relationship between OAT and specific causes of mortality.OBJECTIVE To estimate the association of time receiving OAT with mortality.DATA SOURCES The Embase, MEDLINE, and PsycINFO databases were searched through February 18, 2020, including clinical trial registries and previous Cochrane reviews.STUDY SELECTION All observational studies that collected data on all-cause or cause-specific mortality among people with opioid dependence while receiving and not receiving OAT were included. Randomized clinical trials (RCTs) were also included. DATA EXTRACTION AND SYNTHESISThis systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Data on study, participant, and treatment characteristics were extracted; person-years, all-cause mortality, and cause-specific mortality were calculated. Crude mortality rates and rate ratios (RRs) were pooled using random-effects meta-analyses. MAIN OUTCOMES AND MEASURESOverall all-cause and cause-specific mortality both by setting and by participant characteristics. Methadone and buprenorphine OAT were evaluated specifically. RESULTSFifteen RCTs including 3852 participants and 36 primary cohort studies including 749 634 participants were analyzed. Among the cohort studies, 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). This association was consistent regardless of patient sex, age, geographic location, HIV status, and hepatitis C virus status and whether drugs were taken through injection. Associations were not different for methadone (RR, 0.47; 95% CI, 0.41-0.54) vs buprenorphine (RR, 0.34; 95% CI, 0.26-0.45). There was lower risk of 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 during OAT. In the first 4 weeks of methadone treatment, rates of all-cause mortality and drug-related poisoning were almost double the rates during the remainder of OAT (RR, 2.01; 95% CI, 1.55-5.09) but not for buprenorphine (RR, 0.58; 95% CI, 0.18-1.85). All-cause mortality was 6 times higher in the 4 weeks after OAT cessation (RR, 6.01; 95% CI,, remaining double the rate for the remainder of time not receiving OAT (RR, 1.81; 95% CI, 1.50-2.18). Opioid agonist treatment was associated with a lower risk of mortality during incarceration (RR, 0.06; 95% CI, 0.01-0.46) and after release from incarceration (RR, 0.09; 95% CI, 0.02-0.56). CONCLUSIONS AND RELEVANCEThis systematic review and meta-analysis found that OAT was associated with lower rates of mortality. However, access to OAT remains limited, and coverage of OAT remains ...

Trends in drug poisoning deaths, by sex, in Ireland: a repeated cross-sectional study from 2004 to 2017

“…It is plausible that many clients who died of a drug poisoning death while registered on the OAT register had in fact left treatment because global evidence clearly demonstrates the protective effects of treatment versus leaving treatment. 37 Future work is necessary to ascertain whether the drugs involved in drug poisoning deaths vary depending on where a client is in terms of their OAT journey at the time of death.…”

Impact of the COVID-19 pandemic on opioid agonist treatment in Ireland: Protocol for an interrupted time series analysis

“…Although COVID-19 presents a significant threat to everyone, people with opioid dependence are particularly vulnerable to the disease and its sequelae, as they have a higher burden of co-existing health problems 1 , with many living in areas of social deprivation, with poor-quality housing or homelessness 2 . Opioid agonist treatment (OAT), using methadone or buprenorphine, is the first line treatment for opioid dependence, as it has been shown to be safe and effective in suppressing illicit opioid use 3,4 , improving mental and physical well-being 5 , and reducing mortality 6 . In fact, a recent systematic review identified that risk of all-cause mortality, overdose, suicide, alcohol-related, cancer and cardiovascular-related mortality, were significantly lower for people with opioid dependence on OAT compared to those not on OAT 6 .…”

“…Opioid agonist treatment (OAT), using methadone or buprenorphine, is the first line treatment for opioid dependence, as it has been shown to be safe and effective in suppressing illicit opioid use 3,4 , improving mental and physical well-being 5 , and reducing mortality 6 . In fact, a recent systematic review identified that risk of all-cause mortality, overdose, suicide, alcohol-related, cancer and cardiovascular-related mortality, were significantly lower for people with opioid dependence on OAT compared to those not on OAT 6 . The authors highlighted the importance of increasing access to OAT and maintaining people on OAT who are in critical need of treatment to reduce their mortality risk 6 .…”

“…In fact, a recent systematic review identified that risk of all-cause mortality, overdose, suicide, alcohol-related, cancer and cardiovascular-related mortality, were significantly lower for people with opioid dependence on OAT compared to those not on OAT 6 . The authors highlighted the importance of increasing access to OAT and maintaining people on OAT who are in critical need of treatment to reduce their mortality risk 6 . Methadone is the most common form of OAT in Ireland, and is available free of charge to all persons undergoing OAT for opioid dependence 7 .…”

“…Rapid access to OAT is an important marker of quality of patient care, and COVID-19 has perhaps created an opportunity to increase the number of people entering treatment in Ireland. However, growing evidence suggests that the risk of mortality following dropout from OAT is high 6,7,12 ; therefore, it is also important to review the level of dropout from OAT, alongside numbers in treatment. The aim of this study is to evaluate the impact of the national contingency guidelines introduced from March 2020 on number of patients on OAT, numbers initiating OAT, numbers on waiting list, waiting times, and patient dropout using an interrupted time series (ITS) design.…”