Oxytocin to Enhance Alcohol Behavioral Couple Therapy

摘要 开发治疗酒精使用障碍(AUD)的有效药物疗法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，那些仍然受到温和治疗限制的药物 回应。将药物干预与循证行为干预相结合可能会有所帮助 优化治疗结果。虽然已经开发了几种针对AUD的有效行为干预措施， 绝大多数针对个别患者，尽管有证据表明，对患有AUD的夫妇进行行为干预 优于单独治疗澳元。酒精行为伴侣疗法(ABCT)是一种循证的 对夫妇的行为干预已被证明显著降低了AUD的严重程度并改善了 关系功能是影响AUD治疗结果的重要机制。积累证据 来自我们小组和其他人的研究表明，催产素是一种有希望的候选药物疗法，可以进一步增强 ABCT，降低AUD的严重程度，改善关系功能。先前的研究表明催产素的能力 减少渴求、饮酒、耐受、戒断症状，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)，恢复对自然回报的敏感性(例如，亲密关系)。到目前为止，还没有研究表明 观察催产素联合ABCT治疗AUD的协同作用。因此，主要的 这项第二阶段研究的目标是比较催产素和安慰剂与ABCT联合应用的效果。 降低澳门氏症严重程度，改善人际关系。我们还将利用先进的神经成像技术 治疗前和治疗后的技术研究AUD的基本病理生理学 确定治疗结果的预后指标。要做到这一点，我们将(1)使用双臂 随机、双盲、组间试验设计，包括12周的ABCT治疗 使用催产素或安慰剂；(2)使用标准化的、反复依赖的改变措施，包括酒精 5个时间点的生物标志物(基线、6周、12周以及3个月和6个月的随访)；(3)测量 相关精神和行为健康问题的损害(例如，抑郁)；以及(4)使用功能性 磁共振成像(FMRI)检查皮质边缘连接性的变化。建议进行的研究 直接针对国家酒精滥用和酒精中毒研究所(NIAAA)的使命，因为它的目标是 目的：研究一种新型药理药物治疗AUD的疗效。这项研究的发现 将提供关键的新信息，以帮助为临床实践提供信息，并加快对 AUD的药物治疗。

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.