OBJECTIVE To determine whether 6-month buprenorphine implants are noninferior to daily sublingual buprenorphine as maintenance treatment for opioid-dependent patients with stable abstinence. DESIGN, SETTING, AND PARTICIPANTS Outpatient, randomized, active-controlled, 24-week, double-blind, double-dummy study conducted at 21 US sites from June 26, 2014, through May 18, 2015. Outpatients were prescribed daily sublingual buprenorphine for 6 months or more, were abstinent while taking 8 mg/d or less of sublingual buprenorphine for 90 days or longer, and were determined to be clinically stable by their physician. INTERVENTIONS Participants were randomized to receive sublingual buprenorphine plus 4 placebo implants or sublingual placebo plus four 80-mg buprenorphine hydrochloride implants (expected efficacy, 24 weeks). MAIN OUTCOME MEASURE The primary end point was between-group difference in proportion of responders (Ն4 of 6 months without opioid-positive urine test result [monthly and 4 times randomly] and self-report). The noninferiority established for the lower bound of the 95% confidence interval was greater than −0.20 (P < .025). Secondary end points included cumulative percentage of negative opioid urine results, abstinence, and time to first illicit opioid use. Safety was assessed by adverse event reporting. RESULTS Of 177 participants (mean age, 39 years; 40.9% female), 90 were randomized to sublingual buprenorphine with placebo implants and 87 to buprenorphine implants with sublingual placebo; 165 of 177 (93.2%) completed the trial. Eighty-one of 84 (96.4%) receiving buprenorphine implants and 78 of 89 (87.6%) receiving sublingual buprenorphine were responders, an 8.8% difference (1-sided 97.5% CI, 0.009 to ϱ; P < .001 for noninferiority). Over 6 months, 72 of 84 (85.7%) receiving buprenorphine implants and 64 of 89 (71.9%) receiving sublingual buprenorphine maintained opioid abstinence (hazard ratio, 13.8; 95% CI, 0.018-0.258; P = .03). Non-implant-related and implant-related adverse events occurred in 48.3% and 23% of the buprenorphine implant group and in 52.8% and 13.5% of participants in the sublingual buprenorphine group, respectively. CONCLUSIONS AND RELEVANCE Among adults with opioid dependence maintaining abstinence with a stable dose of sublingual buprenorphine, the use of buprenorphine implants compared with continued sublingual buprenorphine did not result in an inferior likelihood of remaining a responder. However, the study population had an exceptionally high response rate in the control group, and further studies are needed in broader populations to assess the efficacy in other settings.

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The authors conducted a randomized, open comparison of the GABAergic anticonvulsant sodium valproate (divalproex sodium; Depakote) and phenobarbital as an active control in the management of acute withdrawal from alcohol. Repeated measures ANOVA was used to assess treatment effects in the first 37 inpatients, evaluating mood, hostility, and subjective and objective measures of withdrawal at index, 3, and 5 days of detoxification. Subjective and objective ratings of abstinence symptoms and subjective mood disturbance decreased significantly in intensity in both groups over 5 days, but there were no significant treatment differences nor treatment by time interactions. Hostility scores did not differ overall, but a group by time effect was observed (F = 5.42, df = [1,13], P < 0.05), with phenobarbital subjects reporting less hostility/aggression than those in the valproate group. There were no withdrawal-related seizures or other acute sequelae. This study offers pilot confirmation that sodium valproate is as effective as phenobarbital in the management of acute alcohol withdrawal, but it is unclear whether valproate offers a clinical advantage with respect to stabilizing changes in mood and interpersonal hostility during detoxification.

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Background and Objectives: Now more than ever, there is an obvious need to reduce the overall burden of disease and risk of premature mortality that are associated with mental health and substance use disorders among young people. However, the current state of research and evidence-based clinical care for high-risk substance use among youth is fragmented and scarce. The objective of the study is to establish consensus for the prevention, treatment, and management of high-risk substance use and overdose among youth (10 to 24 years old). Materials and Methods: A modified Delphi technique was used based on the combination of scientific evidence and clinical experience of a group of 31 experts representing 10 countries. A semi-structured questionnaire with five domains (clinical risks, target populations, intervention goals, intervention strategies, and settings/expertise) was shared with the panelists. Based on their responses, statements were developed, which were subsequently revised and finalized through three iterations of feedback. Results: Among the five major domains, 60 statements reached consensus. Importantly, experts agreed that screening in primary care and other clinical settings is recommended for all youth, and that the objectives of treating youth with high-risk substance use are to reduce harm and mortality while promoting resilience and healthy development. For all substance use disorders, evidence-based interventions should be available and should be used according to the needs and preferences of the patient. Involuntary admission was the only topic that did not reach consensus, mainly due to its ethical implications and resulting lack of comparable evidence. Conclusions: High-risk substance use and overdoses among youth have become a major challenge. The system’s response has been insufficient and needs substantial change. Internationally devised consensus statements provide a first step in system improvement and reform.