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's protective associations against drug-related poisoning.