Creation of an algorithm for clinical decision support for treatment of opioid use disorder with buprenorphine in primary care.

BACKGROUND: The treatment capacity for opioid use disorder (OUD) lags far behind the number of patients in need of treatment. Capacity is limited, in part, by the limited number of physicians who offer office based OUD treatment with buprenorphine. Measurement based care (MBC) has been proposed as a means to support primary care physicians in treating OUD. Here, we propose a set of measures and a clinical decision support algorithm to provide MBC for the treatment of OUD. METHODS: We utilized literature search and expert consensus to identify measures for universal screening and symptom tracking. We used expert consensus to create the clinical decision support algorithm. RESULTS: The Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) tool was selected as the best published measure for universal screening in primary care. No published measure was identified as appropriate for symptom tracking or medication adherence; therefore, we created the OUD Symptom Checklist from the DSM-5 criteria for OUD and the Patient Adherence Questionnaire for Opioid Use Disorder Treatment (PAQ-OUD) to assess medication adherence. We developed and present a clinical decision support algorithm to provide direct guidance regarding treatment interventions during the first 12 weeks of buprenorphine treatment. CONCLUSION: Creation of these tools is the necessary first step for implementation of MBC for the treatment of OUD with buprenorphine in primary care. Further work is needed to test the feasibility and acceptability of these tools. Trial Registration ClinicalTrials.gov; NCT04059016; 16 August 2019; retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT04059016.

Bupropion and Naltrexone in Methamphetamine Use Disorder.

BACKGROUND: The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied. METHODS: We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone-bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone-bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses. RESULTS: A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone-bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone-bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone-bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone-bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone-bupropion during the trial. CONCLUSIONS: Among adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low but was higher than that among participants who received placebo. (Funded by the National Institute on Drug Abuse and others; ADAPT-2 ClinicalTrials.gov number, NCT03078075.).

Systematic Review of Combined Pharmacotherapy for the Treatment of Alcohol Use Disorder in Patients Without Comorbid Conditions.

BACKGROUND: Previous reviews have examined the use of theoretically supported combinations of drugs for the treatment of alcohol use disorder. This review seeks to examine the strengths and limitations of current clinical evidence for the use of combined pharmacological interventions intended to treat alcohol use disorder. OBJECTIVES: The objective of this review was to identify combinations of pharmacological treatments for alcohol use disorder, and assess the strength of clinical evidence for these treatments. METHODS: We conducted searches using PubMed, EMBASE® through Ovid® (1974 to present), MEDLINE® through Ovid® (1946 to present), and Psychinfo® through Ovid® (1806 to present). Our primary search included the terms "alcoholism" and "drug therapy, combination". Search results were restricted to human subjects and English language. Search criteria were not restricted based on study design or patient age. Studies were evaluated for randomization, blinding, group similarity, power determination, outcome reporting, and number of patients analyzed. RESULTS: Nine hundred and eighty-four publications were initially screened for inclusion after duplicates were removed. The search identified 16 publications evaluating drug combinations for the treatment of alcohol use disorder. The majority of published trials included naltrexone combined with one of the following: gabapentin, ondansetron, acamprosate, gamma-hydroxybutyrate, sertraline, quetiapine, or escitalopram plus gamma-hydroxybutyrate. Other combinations included 5-hydroxytryptophan with carbidopa/levodopa, gamma-hydroxybutyrate with disulfiram, acamprosate with disulfiram, and mirtazapine with quetiapine. Interpretation of results across studies was limited by low statistical power, and heterogeneity of drug combinations and outcome measures. Drug combination effect sizes were comparable to those observed in single-agent trials. CONCLUSIONS: No significant benefit for the use of combinations over single agents was observed. However, benefit may be observed when combined pharmacological interventions address specific symptoms of alcohol use disorder known to be influenced by combination components, or when combinations are used in specific subpopulations in which combination components demonstrate benefit.

Buprenorphine: a review.

A significant breakthrough in the treatment of opioid addiction occurred with the passage of the Data Addiction Treatment Act of 2000 (DATA 2000), signed into law by President Clinton, which allowed physicians for the first time in more than eight decades to prescribe opioid medications for the treatment of opioid addiction in the normal course of their practice. Two years later, on October 8, 2002, Suboxone (Buprenorphine/Naloxone) and Subutex (Buprenorphine) received FDA approval for the treatment of opioid addiction. Prior to DATA 2000, opioid maintenance treatment was available through highly regulated methadone clinics. This article discusses opioid addiction in the United States today and the principles of buprenorphine therapy.