Journal Article Annotations
2017, 3rd Quarter

Substance Use & Addictive Disorders

Annotations by S. Alex Sidelnik, MD, and Diana Robinson, MD
October 2017

Collaborative care for opioid and alcohol use disorders in primary care: the SUMMIT randomized clinical trial
Effect of buprenorphine weekly depot (CAM2038) and hydromorphone blockade in individuals with opioid use disorder: a randomized clinical trial

PUBLICATION #1 — Substance Use & Addictive Disorders

Collaborative care for opioid and alcohol use disorders in primary care: the SUMMIT randomized clinical trial

Watkins KE, Ober AJ, Lamp K, et al

JAMA Intern Med 2017; 177(10):1480-1488

Importance: Primary care offers an important and underutilized setting to deliver treatment for opioid and/or alcohol use disorders (OAUD). Collaborative care (CC) is effective but has not been tested for OAUD.

Objective: To determine whether CC for OAUD improves delivery of evidence-based treatments for OAUD and increases self-reported abstinence compared with usual primary care.

Design, Setting, and Participants: A randomized clinical trial of 377 primary care patients with OAUD was conducted in 2 clinics in a federally qualified health center. Participants were recruited from June 3, 2014 to January 15, 2016 and followed for 6 months.

Interventions: Of the 377 participants, 187 were randomized to CC and 190 were randomized to usual care; 77 (20.4%) of the participants were female, of whom 39 (20.9%) were randomized to CC and 38 (20.0%) were randomized to UC. The mean (SD) age of all respondents at baseline was 42 (12.0) years, 41(11.7) years for the CC group, and 43 (12.2) years for the UC group. Collaborative care was a system-level intervention, designed to increase the delivery of either a 6-session brief psychotherapy treatment and/or medication-assisted treatment with either sublingual buprenorphine/naloxone for opioid use disorders or long-acting injectable naltrexone for alcohol use disorders. Usual care participants were told that the clinic provided OAUD treatment and given a number for appointment scheduling and list of community referrals.

Main Outcomes and Measures: The primary outcomes were use of any evidence-based treatment for OAUD and self-reported abstinence from opioids or alcohol at 6 months. The secondary outcomes included the Healthcare Effectiveness Data and Information Set (HEDIS) initiation and engagement measures, abstinence from other substances, heavy drinking, health-related quality of life, and consequences from OAUD.

Results: At 6 months, the proportion of participants who received any OAUD treatment was higher in the CC group compared with usual care (73 [39.0%] vs 32 [16.8%]; logistic model adjusted OR, 3.97; 95% CI, 2.32-6.79; P < .001). A higher proportion of CC participants reported abstinence from opioids or alcohol at 6 months (32.8% vs 22.3%); after linear probability model adjustment for covariates (β = 0.12; 95% CI, 0.01-0.23; P = .03). In secondary analyses, the proportion meeting the HEDIS initiation and engagement measures was also higher among CC participants (initiation, 31.6% vs 13.7%; adjusted OR, 3.54; 95% CI, 2.02-6.20; P < .001; engagement, 15.5% vs 4.2%; adjusted OR, 5.89; 95% CI, 2.43-14.32; P < .001) as was abstinence from opioids, cocaine, methamphetamines, marijuana, and any alcohol (26.3% vs 15.6%; effect estimate, β = 0.13; 95% CI, 0.03-0.23; P = .01).

Conclusions and Relevance: Among adults with OAUD in primary care, the SUMMIT collaborative care intervention resulted in significantly more access to treatment and abstinence from alcohol and drugs at 6 months, than usual care.

On PubMed: JAMA Intern Med 2017; 177(10):1480-1488

Annotation (Alex Sidelnik)

The finding: A collaborative care intervention for alcohol and opioid use disorders was successfully implemented and led to a significantly increased use of evidence-based treatments including behavioral therapies and medication-assisted treatment in addition to improving self-reported abstinence from opioids and alcohol at six months.

Strength and weaknesses: The study was a multisite, randomized control trial of a collaborative care intervention in over three hundred primary care patients with opioid or alcohol use disorders treated in Federally Qualified Health Centers (FQHCs). The study group received a collaborative care intervention characterized by measurement-based care, pharmacotherapy consultation, care coordination, and access to behavioral treatments while the control group received treatment as usual. The strengths of the study included a diverse study population that may be applicable to other FQHCs, developing a relevant and translatable treatment solution, and utilizing a robust collaborative care intervention. The limitations included potential reporting bias of abstinence due to use of self-reporting, a large number of patients lost to follow-up, and a patient-level rather than clinic-level randomization.

Relevance: As mortality rates from substance used disorders continue to rise, providing access to evidence-based treatments is increasingly necessary. This is the first study showing that a collaborative care intervention for opioid and alcohol use disorders can improve patient outcomes and be implemented effectively in primary care settings.

PUBLICATION #2 — Substance Use & Addictive Disorders

Effect of buprenorphine weekly depot (CAM2038) and hydromorphone blockade in individuals with opioid use disorder: a randomized clinical trial

Walsh SL, Comer SD, Lofwall MR, et al

JAMA Psychiatry 2017; 74(9):894-902

Importance: Buprenorphine is an efficacious, widely used treatment for opioid use disorder (OUD). Daily oral transmucosal formulations can be associated with misuse, diversion, and nonadherence; these limitations may be obviated by a sustained release formulation.

Objective: To evaluate the ability of a novel, weekly, subcutaneous buprenorphine depot formulation, CAM2038, to block euphorigenic opioid effects and suppress opioid withdrawal in non-treatment-seeking individuals with OUD.

Design, Setting, and Participants: This multisite, double-blind, randomized within-patient study was conducted at 3 controlled inpatient research facilities. It involved 47 adults with DSM-V moderate-to-severe OUD. The study was conducted from October 12, 2015 (first patient enrolled), to April 21, 2016 (last patient visit).

Interventions: A total of five 3-day test sessions evaluated the response to hydromorphone (0, 6, and 18 mg intramuscular in random order; 1 dose/session/day). After the first 3-day session (ie, qualification phase), participants were randomized to either CAM2038 weekly at 24 mg (n = 22) or 32 mg (n = 25); the assigned CAM2038 dose was given twice, 1 week apart (day 0 and 7). Four sets of sessions were conducted after randomization (days 1-3, 4-6, 8-10, and 11-13).

Main Outcomes and Measures: The primary end point was maximum rating on the visual analog scale for drug liking. Secondary end points included other visual analog scale (eg, high and desire to use), opioid withdrawal scales, and physiological and pharmacokinetic outcomes.

Results: A total of 46 of 47 randomized participants (mean [SD] age, 35.5 [9] years; 76% male [n = 35]) completed the study. Both weekly CAM2038 doses produced immediate and sustained blockade of hydromorphone effects (liking maximum effect, CAM2038, 24 mg: effect size, 0.813; P < .001, and CAM2038, 32 mg: effect size, 0.753; P < .001) and suppression of withdrawal (Clinical Opiate Withdrawal Scale, CAM2038, 24 mg: effect size, 0.617; P < .001, and CAM2038, 32 mg: effect size, 0.751; P < .001). CAM2038 produces a rapid initial rise of buprenorphine in plasma with maximum concentration around 24 hours, with an apparent half-life of 4 to 5 days and approximately 50% accumulation of trough concentration from first to second dose (trough concentration = 0.822 and 1.23 ng/mL for weeks 1 and 2, respectively, with 24 mg; trough concentration = 0.993 and 1.47 ng/mL for weeks 1 and 2, respectively, with 32 mg).

Conclusions and Relevance: CAM2038 weekly, 24 and 32 mg, was safely tolerated and produced immediate and sustained opioid blockade and withdrawal suppression. The results support the use of this depot formulation for treatment initiation and stabilization of patients with OUD, with the further benefit of obviating the risk for misuse and diversion of daily buprenorphine while retaining its therapeutic benefits.

On PubMed: JAMA Psychiatry 2017; 74(9):894-902

Annotation (Diana Robinson)

The finding: This phase 2 study found that a novel formulation of buprenorphine as a weekly subcutaneous depot formulation was safely tolerated, produced opioid blockade, and suppressed withdrawal. One of 47 patient did not complete the study due to ventricular extra systole. 81% of patients (n=38) experienced one or more adverse events, most commonly constipation (19%) and injection-site pain (11%).

Strength and weaknesses: The strengths of this study included being a multisite, double-blinded, randomized within-patient study in 47 adult patients over a six-month period. The weaknesses of the study include the small sample size, skewed male population (76%), and low racial diversity (50% black and 48% white).

Relevance: As morbidity and mortality rise due to intentional and unintentional overdose on opioids, the development of novel treatments for opioid use disorder is critical. Given the limitations of including daily sublingual buprenorphine can be skipped, misused, and diverted, a safe sustained release formulation may improve treatment of opioid use disorders. A long-acting depot formulation could also be helpful given the scarcity of mental health services in many areas that are particularly afflicted with high rates of opioid use disorders.