Dismantling the Components and Dosing of CBT for Co-Occurring Disorders

描述(申请人提供)：这是最近完成的“家长”R01的竞争性续签申请(AA015069：“CBT治疗酗酒患者的焦虑症”)。在接受酒精使用障碍(AUD)治疗的患者中，多达一半的患者患有共生的焦虑症，这些患者复发饮酒的比率是其他患者的两倍。为了解决这个问题，家长R01评估了一项基于CBT的计划，该计划将三次跨诊断焦虑缓解治疗与三次旨在解除焦虑与酒精使用之间的认知和行为联系的治疗相结合(例如，预期、应对饮酒动机、条件性关联)。在一项有300多个病例的随机试验中，父母R01显示，与增加压力缓解控制治疗(53%复发)相比，在以社区为基础的居民AUD治疗中加入这种CBT显著改善了四个月的酒精结果(例如，41%复发)，与仅接受AUD治疗的匹配的非随机队列(61%复发)相比，显著改善了四个月的酒精结果(例如，41%复发)。虽然这证实了父母R01中的主要研究假设，但必须承认的是，影响并不大，CBT仅缓解了与共生焦虑症相关的增加的复发风险的大约一半。幸运的是，亲本R01的结果也为可能显著提高CBT治疗效果的修饰指明了方向。具体地说，父母R01中的发现模式表明，去偶联疗法，而不是降低焦虑疗法，导致了酒精结果的改善。这表明，进一步强调去偶联治疗元素将增加CBT的整体有效性；然而，减少焦虑对改善这些患者的酒精结果的重要性仍然不明确。例如，致力于减少焦虑的三次会议可能不足以影响父母R01的酒精结果。或者，焦虑减轻疗法可能需要与去偶联疗法协同工作，以改善酒精结果。更新工作将使用拆卸方法来隔离这些治疗组件在两个剂量水平下的单独和相互作用的效果，以实现提高已验证但仍未达到最佳效果的药物的有效性的目标 CBT的父R01版本。350名患有焦虑症的AUD患者将被随机分为三组：1)6次CBT治疗缓解焦虑(CBT-AR)；2)6次CBT治疗焦虑-酒精去偶联(CBT-DC)；或3)原始CBT治疗包括3次焦虑减轻治疗和3次去偶联治疗(CBT-O)。根据Parent R01的研究结果表明去偶联成分是CBT治疗的有效成分，我们预测CBT-DC组(六个DC会话)将获得最好的酒精结果，CBT-O组(三个DC会话)其次是CBT-AR(零DC会话)。如果CBT-O的表现优于其他两组，该设计还将显示AR和DC CBT组件之间的协同效应。

DESCRIPTION (provided by applicant): This is a competitive renewal application for the recently completed "parent" R01 (AA015069: "CBT Treatment for Anxiety Disorder in Comorbid Alcoholics"). Up to half of patients in treatment for an alcohol use disorder (AUD) have a co-occurring anxiety disorder and these patients relapse to drinking at twice the rate of other patients. To address this, the parent R01 evaluated a CBT-based program that combined three sessions of trans-diagnostic anxiety reduction therapy with three sessions designed to de-couple the cognitive and behavioral bonds linking anxiety to alcohol use (e.g., expectancies, coping drinking motives, conditioned associations). In a randomized trial with over 300 cases, the parent R01 showed that adding this CBT to a residential community-based AUD treatment significantly improved four-month alcohol outcomes (e.g., 41% relapsed) compared to adding a stress reduction control treatment (53% relapsed) and compared to a matched, non-randomized cohort undergoing the AUD treatment alone (61% relapsed). While this confirmed the primary study hypotheses in the parent R01, it must be acknowledged that the effects were not large and that the CBT alleviated only about half of the increased relapse risk associated with co- occurring anxiety disorders. Fortunately, the results of the parent R01 also point the way to modifications that are likely to significantly increase the therapeutic effect of the CBT. Specifically, the pattern of findings in the parent R01 indicates that the de-coupling therapy, rather than the anxiety reduction therapy, caused the improved alcohol outcomes. This suggests that further emphasizing the de-coupling therapy elements would increase the CBT's overall effectiveness; however, the importance of anxiety reduction for improving alcohol outcomes in these patients remains ambiguous. For example, the three sessions devoted to anxiety reduction may have been insufficient to affect alcohol outcomes in the parent R01. Alternatively, anxiety reduction therapy may be needed to work synergistically with de-coupling therapy to improve alcohol outcomes. The renewal work would use a dismantling approach to isolate the separate and interactive effects of these therapy components at two dose levels toward the goal of increasing the effectiveness of the validated but still sub-optimally performing parent R01 version of the CBT. 350 AUD patients with an anxiety disorder would be randomized to groups receiving either: 1) six sessions of CBT for anxiety reduction (CBT- AR); 2) six sessions of CBT for anxiety-alcohol de-coupling (CBT-DC); or, 3) the original CBT with its three anxiety reduction sessions and three de-coupling sessions (CBT-O). Based on the parent R01 findings indicating that the de-coupling components are the active ingredients of the CBT therapy, we predict that the best alcohol outcomes will be obtained in the CBT-DC group (six DC sessions) followed by the CBT-O (three DC sessions) further followed by the CBT-AR (zero DC sessions). This design would also indicate synergy effects between the AR and DC CBT components if the CBT-O out-performs the other two groups.