Comparative effectiveness associated with buprenorphine and naltrexone in opioid use disorder and cooccurring polysubstance use

Importance: Despite prevalent polysubstance use, treatment patterns and outcomes for individuals with opioid use disorder (OUD) and cooccurring substance use disorders (SUD) are understudied. Objective: To evaluate the distribution of buprenorphine and naltrexone initiation among individuals with OUD with vs without cooccurring SUD and to assess the comparative effectiveness associated with buprenorphine and naltrexone against drug-related poisonings. Design, Setting, and Participants: This observational comparative effectiveness study used insurance claims from 2011 to 2016 from the US IBM MarketScan databases to study initiation of medications for OUD (MOUD) among treatment-seeking individuals aged 12 to 64 years with a primary diagnosis of OUD. Cooccurring SUD was defined as SUD diagnosed concurrent with or in the 6 months prior to OUD treatment initiation. Treatment was codified as psychosocial treatment without MOUD or initiation or buprenorphine or naltrexone (including extended-release or oral). Methadone recipients were excluded from analysis. Data were analyzed from February 3, 2021, through February 26, 2022. Exposures: MOUD. Main Outcomes and Measures: Associations between cooccurring SUD diagnoses with treatment type were assessed with multivariable regression. The association of drug-related poisoning admissions with days covered with buprenorphine or naltrexone prescriptions vs days without prescriptions was assessed among MOUD initiators. Odds ratios from within-person fixed effects models were estimated as a function of MOUD and stratified by cooccurring SUDs. Results: Among 179 280 individuals with OUD (mean [SD] age, 33.2 [11.0] years; 90 196 [50.5%] men), 102 930 (57.4%) received psychosocial treatment without MOUD. Across 47 488 individuals with cooccurring SUDs, 33 449 (70.4%) did not receive MOUD, whereas across 131 792 individuals without cooccurring SUDs, 69 481 (52.7%) did not receive MOUD. Cooccurring SUD was associated with decreased odds of initiating buprenorphine (risk ratio [RR], 0.55 [95% CI, 0.54-0.56]) but increased odds of initiating naltrexone (extended release: RR, 1.12 [95% CI, 1.05-1.20]; oral: RR, 1.95 [95% CI, 1.86-2.03]). Among 12 485 individuals initiating MOUD who experienced at least 1 drug-related poisoning during insurance enrollment, buprenorphine treatment days were associated with decreased poisonings compared with days without MOUD for individuals with cooccurring SUD (odds ratio [OR], 0.56 [95% CI, 0.48-0.65]) and individuals without cooccurring SUD (OR, 0.57 [95% CI, 0.53-0.63]), with comparable associations observed for extended-release naltrexone. No protective association was observed for oral naltrexone. Conclusions and Relevance: These findings suggest that individuals with OUD and polysubstance use were less likely to initiate buprenorphine and naltrexone than individuals without polysubstance use. Among individuals initiating MOUD, polysubstance use was associated with decreased buprenorphine and increased naltrexone initiation, despite buprenorphine\u27s protective associations against drug-related poisoning

Analysis of stimulant prescriptions and drug-related poisoning risk among persons receiving buprenorphine treatment for opioid use disorder

Importance: Stimulant medication use is common among individuals receiving buprenorphine for opioid use disorder (OUD). Associations between prescription stimulant use and treatment outcomes in this population have been understudied. Objectives: To investigate whether use of prescription stimulants was associated with (1) drug-related poisoning and (2) buprenorphine treatment retention. Design, Setting, and Participants: This retrospective, recurrent-event cohort study with a case-crossover design used a secondary analysis of administrative claims data from IBM MarketScan Commercial and Multi-State Medicaid databases from January 1, 2006, to December 31, 2016. Primary analyses were conducted from March 1 through August 31, 2021. Individuals aged 12 to 64 years with an OUD diagnosis and prescribed buprenorphine who experienced at least 1 drug-related poisoning were included in the analysis. Unit of observation was the person-day. Exposures: Days of active stimulant prescriptions. Main Outcomes and Measures: Primary outcomes were drug-related poisoning and buprenorphine treatment retention. Drug-related poisonings were defined using International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes; treatment retention was defined by continuous treatment claims until a 45-day gap was observed. Results: There were 13 778 567 person-days of observation time among 22 946 individuals (mean [SD] age, 32.8 [11.8] years; 50.3% men) who experienced a drug-related poisoning. Stimulant treatment days were associated with 19% increased odds of drug-related poisoning (odds ratio [OR], 1.19 [95% CI, 1.06-1.34]) compared with nontreatment days; buprenorphine treatment days were associated with 38% decreased odds of poisoning (OR, 0.62 [95% CI, 0.59-0.65]). There were no significant interaction effects between use of stimulants and buprenorphine. Stimulant treatment days were associated with decreased odds of attrition from buprenorphine treatment (OR, 0.64 [95% CI, 0.59-0.70]), indicating that stimulants were associated with 36% longer mean exposure to buprenorphine and its concomitant protection. Conclusions and Relevance: Among persons with OUD, use of prescription stimulants was associated with a modest increase in per-day risk of drug-related poisoning, but this risk was offset by the association between stimulant use and improved retention to buprenorphine treatment, which is associated with protection against overdose

Comparative effectiveness associated with buprenorphine and naltrexone in opioid use disorder and cooccurring polysubstance use.

Question: What is the prevalence and comparative effectiveness associated with buprenorphine and naltrexone in individuals with opioid use disorder (OUD) and cooccurring substance use disorders (SUDs)? Findings: This comparative effectiveness study evaluated 179 280 individuals with OUD using insurance claims. Individuals with OUD and co-occurring SUDs were less likely to receive buprenorphine and more likely to receive extended-release naltrexone than peers without polysubstance use; buprenorphine and extended-release naltrexone were comparable in their protective associations with drug-related poisonings in both populations. Meaning: These findings suggest that individuals with cooccurring SUDs were less likely to receive buprenorphine despite buprenorphine’s association with protecting against overdose in this population

Association of opioid use disorder treatment with alcohol-related acute events.

Importance: Persons with opioid use disorder (OUD) and co-occurring alcohol use disorder (AUD) are understudied and undertreated. It is unknown whether the use of medications to treat OUD is associated with reduced risk of alcohol-related morbidity. Objective: To determine whether the use of OUD medications is associated with decreased risk for alcohol-related falls, injuries, and poisonings in persons with OUD with and without co-occurring AUD. Design, Setting, and Participants: This recurrent-event, case-control, cohort study used prescription claims from IBM MarketScan insurance databases from January 1, 2006, to December 31, 2016. The sample included persons aged 12 to 64 years in the US with an OUD diagnosis and taking OUD medication who had at least 1 alcohol-related admission. The unit of observation was person-day. Data analysis was performed from June 26 through September 28, 2020. Exposures: Days of active OUD medication prescriptions, with either agonist (ie, buprenorphine or methadone) or antagonist (ie, oral or extended-release naltrexone) treatments compared with days without OUD prescriptions. Main Outcomes and Measures: The primary outcome was admission for any acute alcohol-related event defined by International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Conditional logistic regression was used to compare OUD medication use between days with and without an alcohol-related event. Stratified analyses were conducted between patients with OUD with and without a recent AUD diagnostic code. Results: There were 8 424 214 person-days of observation time among 13 335 participants who received OUD medications and experienced an alcohol-related admission (mean [SD] age, 33.1 [13.1] years; 5884 female participants [44.1%]). Agonist treatments (buprenorphine and methadone) were associated with reductions in the odds of any alcohol-related acute event compared with nontreatment days, with a 43% reduction for buprenorphine (odds ratio [OR], 0.57; 95% CI, 0.52-0.61) and a 66% reduction for methadone (OR, 0.34; 95% CI, 0.26-0.45). The antagonist treatment naltrexone was associated with reductions in alcohol-related acute events compared with nonmedication days, with a 37% reduction for extended-release naltrexone (OR, 0.63; 95% CI, 0.52-0.76) and a 16% reduction for oral naltrexone (OR, 0.84; 95% CI, 0.76-0.93). Naltrexone use was more prevalent among patients with OUD with recent AUD claims than their peers without AUD claims. Conclusions and Relevance: These findings suggest that OUD medication is associated with fewer admissions for alcohol-related acute events in patients with OUD with co-occurring AUD

Analysis of stimulant prescriptions and drug-related poisoning risk among persons receiving buprenorphine treatment for opioid use disorder.

Key Points: Question: How are use of prescription stimulants associated with treatment outcomes in persons with opioid use disorder (OUD)? Findings: In this cohort study of 22 946 persons with OUD receiving buprenorphine treatment, stimulant treatment days were associated with 19% increased odds of drug-related poisoning and 36% decreased risk of attrition from buprenorphine treatment. Meaning: These findings suggest that among persons with OUD who have experienced a drug-related poisoning, stimulant use is associated with a modest increased risk of drug-related poisoning that may be offset by longer duration of buprenorphine treatment, which is associated with protection against overdose