Oxytocin to Enhance Alcohol Behavioral Couple Therapy

摘要 开发有效的药物治疗酒精使用障碍（AUD）是公共卫生的优先事项。 目前很少有药物被批准用于治疗AUD，并且那些药物仍然受到适度治疗的限制 应答将药物干预与循证行为干预相结合可能会有所帮助 优化治疗效果。虽然已经开发了几种有效的AUD行为干预措施， 绝大多数针对个体患者，尽管有证据表明，对患有AUD的夫妇进行行为干预 优于澳元的单独治疗。酒精行为夫妻治疗（ABCT）是一种基于证据的治疗方法。 对夫妇进行行为干预，已被证明可显著降低AUD的严重程度， 关系功能，这是AUD治疗结果的重要机制。越来越多的证据 来自我们小组和其他人的研究表明，催产素是一种有前途的候选药物疗法，可以进一步增强 ABCT，降低AUD严重程度，改善关系功能。先前的研究表明催产素能够 减少渴望，酒精消费，耐受和戒断症状，并改善神经生物学 与澳元相关的赤字。此外，催产素已被证明可以增加亲社会因素（例如，信任， 社会认知）和恢复对自然回报的敏感性（例如，亲密关系）。到目前为止，没有任何研究 研究了催产素与ABCT联合治疗AUD的协同作用。因此，主要 本阶段II研究的目的是检查催产素与安慰剂联合ABCT在 降低AUD严重程度并改善关系功能。我们还将利用先进的神经成像技术 治疗前后的技术，以研究夫妇之间AUD的潜在病理生理学， 确定治疗结果的预后指标。为了做到这一点，我们将（1）采用双臂 随机、双盲、组间实验设计，包括12周ABCT治疗 使用催产素或安慰剂;（2）使用标准化的，重复的依赖性变化措施，包括酒精 在五个时间点（基线、第6周、第12周以及3个月和6个月随访）测量生物标志物;（3）测量 相关精神和行为健康问题的损害（例如，抑郁症）;（4）使用功能性 磁共振成像（fMRI）检查皮质边缘连接的变化。拟定研究 直接解决了国家酒精滥用和酒精中毒研究所（NIAAA）的使命， 研究一种新型药物治疗AUD的疗效。这项研究的结果 将提供重要的新信息，以帮助通知临床实践，并加快对 药物治疗AUD。

ABSTRACT The development of effective pharmacotherapies to treat alcohol use disorder (AUD) is a public health priority. Few medications are currently approved to treat AUD and those that are remain limited by modest treatment responses. Combining pharmacological interventions with evidence-based behavioral interventions may help optimize treatment outcomes. While several effective behavioral interventions for AUD have been developed, the vast majority target individual patients, despite evidence that behavioral interventions for couples with AUD outperform individual treatments for AUD. Alcohol Behavioral Couples Therapy (ABCT) is an evidence-based behavioral intervention for couples that has been shown to significantly reduce AUD severity as well as improve relationship functioning, which is an important mechanism in treatment outcome for AUD. Accumulating evidence from our group and others suggests that oxytocin is a promising candidate pharmacotherapy to further enhance ABCT, reduce AUD severity and improve relationship functioning. Previous studies demonstrate oxytocin's ability to reduce craving, alcohol consumption, symptoms of tolerance and withdrawal, and ameliorate neurobiological deficits associated with AUD. Furthermore, oxytocin has been shown to increase prosocial factors (e.g., trust, social cognition) and restore sensitivity to natural rewards (e.g., intimate relationships). To date, no studies have examined the synergistic effects of combining oxytocin with ABCT in the treatment of AUD. Thus, the primary objective of this Stage II study is to examine the effects of oxytocin versus placebo in combination with ABCT in reducing AUD severity and improving relationship functioning. We will also utilize advanced neuroimaging techniques before and after treatment to investigate the underlying pathophysiology of AUD among couples and identify prognostic indicators of treatment outcome. To accomplish this, we will (1) employ a two-arm randomized, double-blind, between-groups experimental design that will consist of 12 weeks of ABCT treatment with oxytocin or placebo; (2) use standardized, repeated dependent measures of change including alcohol biomarkers at five time points (baseline, week 6, week 12, and 3- and 6-month follow-up); (3) measure impairment in associated mental and behavioral health problems (e.g., depression); and (4) use functional magnetic resonance imaging (fMRI) to examine changes in corticolimbic connectivity. The proposed study directly addresses the mission of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in that it aims to examine the efficacy of a novel pharmacologic agent for the treatment of AUD. The findings from this study will provide critical new information to help inform clinical practice and accelerate research on the pharmacological treatment of AUD.