This Clinical Insights describes the process for initiating buprenorphine treatment for patients with opioid use disorder.
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.
Importance: Buprenorphine treatment for opioid use disorder may be improved by sustained-release formulations.
Objective: To determine whether treatment involving novel weekly and monthly subcutaneous (SC) buprenorphine depot formulations is noninferior to a daily sublingual (SL) combination of buprenorphine hydrochloride and naloxone hydrochloride in the treatment of opioid use disorder.
Design, setting, and participants: This outpatient, double-blind, double-dummy randomized clinical trial was conducted at 35 sites in the United States from December 29, 2015, through October 19, 2016. Participants were treatment-seeking adults with moderate-to-severe opioid use disorder.
Interventions: Randomization to daily SL placebo and weekly (first 12 weeks; phase 1) and monthly (last 12 weeks; phase 2) SC buprenorphine (SC-BPN group) or to daily SL buprenorphine with naloxone (24 weeks) with matched weekly and monthly SC placebo injections (SL-BPN/NX group).
Main outcomes and measures: Primary end points tested for noninferiority were response rate (10% margin) and the mean proportion of opioid-negative urine samples for 24 weeks (11% margin). Responder status was defined as having no evidence of illicit opioid use for at least 8 of 10 prespecified points during weeks 9 to 24, with 2 of these at week 12 and during month 6 (weeks 21-24). The mean proportion of samples with no evidence of illicit opioid use (weeks 4-24) evaluated by a cumulative distribution function (CDF) was an a priori secondary outcome with planned superiority testing if the response rate demonstrated noninferiority.
Results: A total of 428 participants (263 men [61.4%] and 165 women [38.6%]; mean [SD] age, 38.4 [11.0] years) were randomized to the SL-BPN/NX group (n = 215) or the SC-BPN group (n = 213). The response rates were 31 of 215 (14.4%) for the SL-BPN/NX group and 37 of 213 (17.4%) for the SC-BPN group, a 3.0% difference (95% CI, -4.0% to 9.9%; P < .001). The proportion of opioid-negative urine samples was 1099 of 3870 (28.4%) for the SL-BPN/NX group and 1347 of 3834 (35.1%) for the SC-BPN group, a 6.7% difference (95% CI, -0.1% to 13.6%; P < .001). The CDF for the SC-BPN group (26.7%) was statistically superior to the CDF for the SL-BPN/NX group (0; P = .004). Injection site adverse events (none severe) occurred in 48 participants (22.3%) in the SL-BPN/NX group and 40 (18.8%) in the SC-BPN group.
Conclusions and relevance: Compared with SL buprenorphine, depot buprenorphine did not result in an inferior likelihood of being a responder or having urine test results negative for opioids and produced superior results on the CDF of no illicit opioid use. These data suggest that depot buprenorphine is efficacious and may have advantages.
Objectives. Chronic pain is common, and opioid therapy is frequently prescribed for this condition. This report updates and expands on a prior Comparative Effectiveness Review on long-term (≥1 year) effectiveness and harms of opioid therapy for chronic pain, including evidence on shorter term (1 to 12 months) outcomes.
Data sources. A prior systematic review (searches through January 2014), electronic databases (Ovid MEDLINE®, Embase®, PsycINFO®, Cochrane CENTRAL, and Cochrane Database of Systematic Reviews through August 2019), reference lists, and clinical trials registries.
Review methods. Predefined criteria were used to select studies of patients with chronic pain prescribed opioids that addressed effectiveness or harms versus placebo, no opioid use, or nonopioid pharmacological therapies; different opioid dosing methods; or risk mitigation strategies. Effects were analyzed at short-term (1 to <6 months), intermediate-term (≥6 to <12 months), and long-term (≥12 months) followup. Studies on the accuracy of risk prediction instruments for predicting opioid use disorder or misuse were also included. Random effects meta-analysis was conducted on short-term trials of opioids versus placebo, opioids versus nonopioids, and opioids plus nonopioids versus an opioid or nonopioid alone. Magnitude of effects was classified as small, moderate, or large using predefined criteria, and strength of evidence was assessed.
Results. We included 115 randomized controlled trials (RCTs), 40 observational studies, and 7 studies of predictive accuracy; 134 were new to this update. Opioids were associated with small benefits versus placebo in short-term pain, function, and sleep quality. There was a small dose-dependent effect on pain, and effects were attenuated at longer (3 to 6 month) versus shorter (1 to 3 month) followup. Opioids were associated with increased risk of discontinuation due to adverse events, gastrointestinal adverse events, somnolence, dizziness, and pruritus versus placebo. In observational studies, opioids were associated with increased risk of an opioid abuse or dependence diagnosis, overdose, all-cause mortality, fractures, falls, and myocardial infarction versus no opioid use; there was evidence of a dose-dependent risk for all outcomes except fracture and falls.
There were no differences between opioids and nonopioid medications in pain, function, or other short-term outcomes. Opioid plus nonopioid combination therapy was associated with little improvement in pain at short-term followup versus an opioid alone. Co-prescription of benzodiazepines or gabapentinoids was associated with increased risk of overdose versus an opioid alone. No RCT evaluated intermediate- or long-term benefits of opioids versus placebo. One trial found stepped therapy starting with opioids to be associated with higher pain intensity and no difference in function or other outcomes versus stepped therapy starting with nonopioid therapy.
Limited evidence indicated no differences between long- and short-acting opioids in effectiveness, but long-acting opioids were associated with increased risk of overdose. One RCT found a taper support intervention associated with greater improvement in function but no difference in pain versus usual care.
Estimates of diagnostic accuracy for various risk prediction instruments were highly inconsistent, and there was no evidence on the effectiveness of risk mitigation strategies for improving clinical outcomes, with the exception of one study that found provision of naloxone associated with decreased emergency department visits.
Trials of patients with prescription opioid dependence found buprenorphine maintenance associated with better outcomes than buprenorphine taper and similar effects of methadone versus buprenorphine. Evidence was insufficient to evaluate benefits and harms of opioid therapy in patients at higher risk for opioid use disorder.
Conclusions. At short-term followup, for patients with chronic pain, opioids are associated with small beneficial effects versus placebo but are associated with increased risk of short-term harms and do not appear to be superior to nonopioid therapy. Evidence on intermediate-term and long-term benefits remains very limited, and additional evidence confirms an association between opioids and increased risk of serious harms that appears to be dose-dependent. Research is needed to develop accurate risk prediction instruments, determine effective risk mitigation strategies, clarify risks associated with co-prescribed medications, and identify optimal opioid tapering strategies.
IMPORTANCE:
Although clinical trials demonstrate the superior effectiveness of medication for opioid use disorder (MOUD) compared with nonpharmacologic treatment, national data on the comparative effectiveness of real-world treatment pathways are lacking.
OBJECTIVE:
To examine associations between opioid use disorder (OUD) treatment pathways and overdose and opioid-related acute care use as proxies for OUD recurrence.
DESIGN, SETTING, AND PARTICIPANTS:
This retrospective comparative effectiveness research study assessed deidentified claims from the OptumLabs Data Warehouse from individuals aged 16 years or older with OUD and commercial or Medicare Advantage coverage. Opioid use disorder was identified based on 1 or more inpatient or 2 or more outpatient claims for OUD diagnosis codes within 3 months of each other; 1 or more claims for OUD plus diagnosis codes for opioid-related overdose, injection-related infection, or inpatient detoxification or residential services; or MOUD claims between January 1, 2015, and September 30, 2017. Data analysis was performed from April 1, 2018, to June 30, 2019.
EXPOSURES:
One of 6 mutually exclusive treatment pathways, including (1) no treatment, (2) inpatient detoxification or residential services, (3) intensive behavioral health, (4) buprenorphine or methadone, (5) naltrexone, and (6) nonintensive behavioral health.
MAIN OUTCOMES AND MEASURES:
Opioid-related overdose or serious acute care use during 3 and 12 months after initial treatment.
RESULTS:
A total of 40 885 individuals with OUD (mean [SD] age, 47.73 [17.25] years; 22 172 [54.2%] male; 30 332 [74.2%] white) were identified. For OUD treatment, 24 258 (59.3%) received nonintensive behavioral health, 6455 (15.8%) received inpatient detoxification or residential services, 5123 (12.5%) received MOUD treatment with buprenorphine or methadone, 1970 (4.8%) received intensive behavioral health, and 963 (2.4%) received MOUD treatment with naltrexone. During 3-month follow-up, 707 participants (1.7%) experienced an overdose, and 773 (1.9%) had serious opioid-related acute care use. Only treatment with buprenorphine or methadone was associated with a reduced risk of overdose during 3-month (adjusted hazard ratio [AHR], 0.24; 95% CI, 0.14-0.41) and 12-month (AHR, 0.41; 95% CI, 0.31-0.55) follow-up. Treatment with buprenorphine or methadone was also associated with reduction in serious opioid-related acute care use during 3-month (AHR, 0.68; 95% CI, 0.47-0.99) and 12-month (AHR, 0.74; 95% CI, 0.58-0.95) follow-up.
CONCLUSIONS AND RELEVANCE:
Treatment with buprenorphine or methadone was associated with reductions in overdose and serious opioid-related acute care use compared with other treatments. Strategies to address the underuse of MOUD are needed.
The United States is in the midst of a national opioid epidemic. Physicians are encouraged both to prevent and treat opioid-use disorders (OUDs). Although there are 3 Food and Drug Administration-approved medications to treat OUD (methadone, buprenorphine, and naltrexone) and there is ample evidence of their efficacy, they are not used as often as they should. We provide a brief review of the 3 primary medications used in the treatment of OUD. Using data from available medical literature, we synthesize existing knowledge and provide a framework for how to determine the optimal approach for outpatient management of OUD with medication-assisted treatments.
Opioids were involved in 42,249 deaths in the United States in 2016, and opioid overdoses have quintupled since 1999.1 Among the causes behind these statistics is increased opiate prescribing by physicians—with primary care providers accounting for about one half of opiate prescriptions.2 As a result, the Centers for Disease Control and Prevention has issued a 4-part response for physicians,3 which includes careful opiate prescribing, expanded access to naloxone, prevention of opioid use disorder (OUD), and expanded use of medication-assisted treatment (MAT) of addiction— with the goal of preventing and managing OUD.
