Abstract
IMPORTANCE: Several large, randomized clinical trials have tested the efficacy of adding behavioral therapy to medical management (high-quality, low-intensity medical counseling) and buprenorphine treatment of opioid use disorder. These studies have consistently reported strong rates of treatment response overall, without a significant additive benefit of additional behavioral therapy. OBJECTIVE: To address gaps in knowledge about additional behavioral therapy for patients receiving buprenorphine, including the association of additional behavioral therapy with retention and functional outcomes, and whether certain subgroups respond better to additional behavioral therapy. DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of 4 randomized clinical trials conducted in Connecticut, Southern California, and 10 other US sites between 2000 and 2011. Participants included adults with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) opioid dependence. Analyses were conducted between January 2024 and July 2025. EXPOSURE: Buprenorphine and varying levels of behavioral therapy, including standard medical management, physician management, physician management plus cognitive behavioral therapy, contingency management, contingency management plus cognitive behavioral therapy, standard medical management plus opioid dependence counseling, or no additional behavioral treatment. MAIN OUTCOMES AND MEASURES: The main outcomes included weeks of buprenorphine retention and functioning across 7 domains (medical, employment and financial support, social and family, alcohol, drug, legal, and psychiatric), assessed using the Addiction Severity Index. Data on additional behavioral therapy (structured cognitive-behavioral and counseling approaches) combined with buprenorphine and medical management were harmonized to provide needed statistical power for considering moderation effects. RESULTS: The combined sample consisted of 869 adults (mean [SD] age, 34.2 [10.4] years; 287 female [33%]). Results demonstrated that additional behavioral therapy was not associated with opioid-free weeks (mean [SD] number of opioid-free weeks, 7.16 [4.35]) compared with medical management and buprenorphine (mean [SD] number of opioid-free weeks, 7.00 [4.33]) (B = 0.28; 95% CI, -0.33 to 0.89; P = .37). Additional behavioral therapy was also not associated with greater buprenorphine retention (mean [SD] number of weeks of buprenorphine, 10.29 [3.21] out of 12) compared with medical management and buprenorphine (mean [SD] number of weeks of buprenorphine, 10.21 [3.15]) (B = 0.00; 95% CI, -0.43 to 0.43; P = .98). Measures of functioning indicated minimal change over the course of treatment, and there were no differences between randomized groups. No moderational effects of subgroups (eg, history of heroin use) were significant when correcting for multiple comparisons. CONCLUSIONS AND RELEVANCE: In this secondary analysis of 4 randomized clinical trials, results highlighted the strong efficacy of buprenorphine treatment when combined with medical management for opioid use disorder. Although there was certainly room for improvement in outcomes-particularly functioning-trials of novel adjuncts for buprenorphine treatment may encounter statistical power challenges outperforming such a robust control condition. TRIAL REGISTRATION: NCT00316277, NCT00591617, NCT00632151, NCT00023283.