Real-world effectiveness of pharmacological treatments of opioid use disorder in a national cohort

Aim To investigate the real-world effectiveness of pharmacological treatments (buprenorphine, methadone) of opioid use disorder (OUD). Design A nation-wide, register-based cohort study. Setting Sweden. Participants All residents aged 16-64 years living in Sweden using OUD medication from July 2005 to December 2016 (n = 5757, 71.8% men) were identified from registers of prescriptions, inpatient and specialized outpatient care, causes of death, sickness absence and disability pensions. Measurements Main outcome: hospitalization due to OUD. Secondary outcomes: hospitalization due to any cause; death due to all, natural and external causes. Mortality was analyzed with between-individual multivariate-adjusted Cox hazards regression model. Recurrent outcomes, such as hospitalizations, were analyzed with within-individual analyses to eliminate selection bias. OUD medication use versus non-use was modelled with PRE2DUP (from prescription drug purchases to drug use periods) method. Findings Buprenorphine [hazard ratio (HR) = 0.73, 95% confidence interval (CI) = 0.54-0.97] and methadone (HR = 0.74, 95% CI = 0.59-0.93) use were associated with significantly lower risk of OUD hospitalization, but not any-cause hospitalizations, compared with the time-periods when the same individual did not use OUD medication. The use of buprenorphine and methadone were both associated with significantly lower risk of all-cause mortality (HR = 0.45, 95% CI = 0.34-0.59; HR = 0.51, 95% CI = 0.41-0.63, respectively), compared with non-use of both medications. Similar results were found for risk of mortality due to external causes (HR = 0.39; 95% CI = 0.27-0.54; HR = 0.40; 95% CI = 0.29-0.53, respectively), but not for mortality due to natural causes. The risk of OUD hospitalization and all-cause mortality was decreased in all duration categories of studied medications (< 30, 31-180, 181-365 and >365 days), except for methadone use less than 30 days. Conclusions The use of buprenorphine and methadone are both associated with a significantly lower risk of hospitalization due to opioid use disorder and death due to all and external causes, when compared with non-use.