McHugh R Kathryn, Bailey Allen J, McConaghy Brooke A, Weiss Roger D, Fiellin David A, Hillhouse Maureen, Moore Brent A, Fitzmaurice Garrett M
Division of Alcohol, Drugs and Addiction, McLean Hospital, Belmont, Massachusetts.
Department of Psychiatry, Harvard Medical School, Cambridge Massachusetts.
JAMA Netw Open. 2025 Aug 1;8(8):e2528529. doi: 10.1001/jamanetworkopen.2025.28529.
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.
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.
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.
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.
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.
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.
NCT00316277, NCT00591617, NCT00632151, NCT00023283.
多项大型随机临床试验检验了在药物治疗（高质量、低强度药物咨询）和丁丙诺啡治疗阿片类物质使用障碍基础上增加行为疗法的疗效。这些研究一直报告总体治疗反应率很高，额外的行为疗法并无显著的附加益处。
解决关于接受丁丙诺啡治疗的患者额外行为疗法的知识空白，包括额外行为疗法与留存率及功能结局的关联，以及某些亚组是否对额外行为疗法反应更好。
设计、设置和参与者：本研究是对2000年至2011年在康涅狄格州、南加利福尼亚州和美国其他10个地点进行的4项随机临床试验的二次分析。参与者包括符合《精神障碍诊断与统计手册》（第四版）阿片类物质依赖诊断标准的成年人。分析于2024年1月至2025年7月进行。
丁丙诺啡和不同水平的行为疗法，包括标准药物治疗、医生管理、医生管理加认知行为疗法、应急管理、应急管理加认知行为疗法、标准药物治疗加阿片类物质依赖咨询，或无额外行为治疗。
主要结局包括丁丙诺啡的留存周数以及在7个领域（医疗、就业和经济支持、社交和家庭、酒精、药物、法律和精神）的功能状况，使用成瘾严重程度指数进行评估。将额外行为疗法（结构化认知行为和咨询方法）与丁丙诺啡和药物治疗相结合的数据进行整合，以提供考虑调节效应所需的统计效力。
合并样本包括869名成年人（平均[标准差]年龄为34.2[10.4]岁；287名女性[33%]）。结果表明，与药物治疗和丁丙诺啡相比，额外行为疗法与无阿片类物质周数（平均[标准差]无阿片类物质周数为7.16[4.35]）无关（平均[标准差]无阿片类物质周数为7.00[4.33]）（B = 0.28；95%置信区间为-0.33至0.89；P = 0.37）。与药物治疗和丁丙诺啡相比，额外行为疗法与更高的丁丙诺啡留存率（在12周中丁丙诺啡的平均[标准差]周数为10.29[3.21]）也无关（丁丙诺啡的平均[标准差]周数为10.21[3.15]）（B = 0.00；95%置信区间为-0.43至0.43；P = 0.98）。功能测量指标表明治疗过程中变化极小，随机分组之间无差异。在进行多重比较校正后，亚组（如使用海洛因史）的调节效应均不显著。
在对4项随机临床试验的这项二次分析中，结果突出了丁丙诺啡治疗与药物治疗相结合用于阿片类物质使用障碍时的强大疗效。尽管结局尤其是功能方面肯定有改善空间，但丁丙诺啡治疗新型辅助手段的试验可能会遇到统计效力挑战，难以超越如此强大的对照条件。
NCT00316277、NCT00591617、NCT00632151、NCT00023283。
