Context No randomized trials have examined treatments for prescription opioid dependence, despite its increasing prevalence. Objective To evaluate the efficacy of brief and extended buprenorphine-naloxone treatment, with different counseling intensities, for patients dependent upon prescription opioids. Setting, Participants 653 treatment-seeking outpatients dependent on prescription opioids, at 10 U.S. sites from June 2006-July 2009. Design Multi-site, randomized clinical trial, using a two-phase adaptive treatment research design. Brief treatment (Phase 1) included 2-week buprenorphine-naloxone stabilization, 2-week taper, and 8-week post-medication follow-up. Patients with successful opioid use outcomes exited the study; unsuccessful patients entered Phase 2: extended (12-week) buprenorphine-naloxone treatment, 4-week taper, and 8-week post-medication follow-up. Main outcome measures Pre-defined “successful outcome” in each phase: composite measures indicating minimal or no opioid use, based on urine-confirmed self-reports. Interventions In both phases, patients were randomized to Standard Medical Management (SMM) or SMM+Opioid Drug Counseling (ODC); all received buprenorphine-naloxone. Results During Phase 1, only 6.6% (43/653) of patients had successful outcomes, with no difference between the SMM and SMM+ODC. In contrast, 49.2% (177/360) attained successful outcomes in Phase 2 during extended buprenorphine-naloxone treatment (week 12), with no difference between counseling conditions. Success rates 8 weeks after completing the buprenorphine-naloxone taper (Phase 2, week 24) dropped sharply to 8.6% (31/360), again with no counseling difference. In secondary analyses, successful Phase 2 outcomes were far more common while taking buprenorphine-naloxone than 8 weeks post-taper (49.2% (177/360) vs. 8.6% (31/360), p<0.001). Chronic pain did not affect opioid use outcomes; a history of ever using heroin was associated with lower Phase 2 success rates while taking buprenorphine-naloxone. Conclusions Prescription opioid-dependent patients are most likely to reduce opioid use during buprenorphine-naloxone treatment; if tapered off buprenorphine-naloxone, even after 12 weeks of treatment, the likelihood of unsuccessful outcome is extremely high, even among patients receiving counseling in addition to medical management. Trial Registration ClinicalTrials.gov number NCT00316277

Medication-assisted treatment of opioid use disorder with physiological dependence at least doubles rates of opioid-abstinence outcomes in randomized, controlled trials comparing psychosocial treatment of opioid use disorder with medication versus with placebo or no medication. This article reviews the current evidence for medication-assisted treatment of opioid use disorder and also presents clinical practice imperatives for preventing opioid overdose and the transmission of infectious disease. The evidence strongly supports the use of agonist therapies to reduce opioid use and to retain patients in treatment, with methadone maintenance remaining the gold standard of care. Combined buprenorphine/naloxone, however, also demonstrates significant efficacy and favorable safety and tolerability in multiple populations, including youth and prescription opioid-dependent individuals, as does buprenorphine monotherapy in pregnant women. The evidence for antagonist therapies is weak. Oral naltrexone demonstrates poor adherence and increased mortality rates, although the early evidence looks more favorable for extended-release naltrexone, which has the advantages that it is not subject to misuse or diversion and that it does not present a risk of overdose on its own. Two perspectives-individualized treatment and population management-are presented for selecting among the three available Food and Drug Administration-approved maintenance therapies for opioid use disorder. The currently unmet challenges in treating opioid use disorder are discussed, as are the directions for future research.

Although gender differences in substance use disorders have been identified, few studies have examined gender differences in prescription drug dependence. The aim of this study was to examine gender differences in clinical characteristics and treatment outcomes in a large clinical trial for prescription opioid dependence. Despite no pre-treatment differences in opioid dependence severity, women reported significantly greater functional impairment, greater psychiatric severity, and higher likelihood of using opioids to cope with negative affect and pain than men. Women were also more likely than men to have first obtained opioids via a legitimate prescription and to use opioids via the intended route of administration. Men reported significantly more alcohol problems than women. There were no significant gender differences in medication dose, treatment retention, or opioid outcomes. Thus, despite the presence of pre-treatment gender differences in this population, once the study treatment was initiated, women and men exhibited similar opioid use outcomes.