Cognitive Behavioral Therapy (CBT-I) Augmentation of Topiramate in promoting abstinence in alcohol use disorder (AUD).

摘要 酒精使用障碍(AUD)和失眠在退伍军人中比一般人更普遍 人口。虽然失眠症在澳大利亚的患病率是普通人群的3-9倍，但患有失眠症的患者 并发AUD和失眠症的AUD严重程度更高，酒精渴求增加，质量下降 生活质量差，人际功能受损，自杀行为的风险较高，以及早期复发 禁欲。由于副作用的影响，治疗饮酒行为和失眠的选择有限 (双硫兰)或仅对饮酒结果有轻微影响(纳曲酮和氨基己酸酯)。托吡酯(上)，一个 FDA批准的治疗癫痫和偏头痛的药物在实现戒断方面显示出中等效果 在最近的一项荟萃分析中，与安慰剂相比，减少了渴望。然而，顶级疗法并没有 在客观睡眠或主观失眠方面提供临床改善。此外，催眠药物 曲唑酮、加巴喷丁和雷美泰的治疗对睡眠障碍和 禁欲。相比之下，评估失眠认知行为疗法(CBT-I)的所有四项研究都 在治疗失眠方面显示出很大的效果，但对戒酒的影响很小或没有。因此， TOP和CBT-I的结合将加强他们的恢复并改善他们的整体功能。这 联合治疗将是治疗退伍军人AUD和共病的第一个个性化干预 失眠。 一名患有AUD(N=174)的寻求治疗的退伍军人最初将接受TOP 200 mg a治疗 连续6周，然后随机接受CBT-I(N=87)或睡眠卫生教育(SHE，A 行为安慰剂干预)(N=87)，在接下来的八周内每周进行一次。我们将进行CBT-I，遵循我们的 使用30分钟会话的标准协议来提供其组件(睡眠限制、刺激控制、 睡眠卫生学和认知疗法)。干预后的访问将在干预后8周进行 干预阶段。主要结果衡量标准将是禁欲天数的百分比(根据 时间线跟踪采访)和失眠严重程度(使用失眠严重程度指数进行评估)。 此外，我们还将使用TLFB、PACS、睡眠日记、 BDI和STAI来测试饮酒和失眠的成功治疗是否会与更好的 AUD的临床结果。假设在患有AUD的退伍军人中，TOP+CBT-I和AS的组合 与TOP+SHE组相比，1)戒酒天数比例更高，以及 2)卓越的睡眠相关结果以及可与Meta分析相媲美的治疗前效果大小 规范。如果这些假设得到支持，这些发现将需要在一项更大的多中心试验中得到验证。如果 经过验证，研究结果将支持：1)将失眠治疗作为初始计划的标准组成部分 AUD合并失眠的治疗方案；2)采用TOP+CBT-I联合治疗 这一亚群的AUD患者。

Abstract Alcohol Use Disorder (AUD) and insomnia are both more prevalent among Veterans than in the general population. While insomnia is 3-9 times more prevalent in AUD than in the general population, patients with comorbid AUD and insomnia suffer from higher severity of AUD with increased alcohol craving, reduced quality of life, impaired interpersonal functioning, higher risks for suicidal behavior and relapse during early abstinence. There are limited options to treat drinking behavior and insomnia due to side effect profile (disulfiram) or only modest impact on drinking outcomes (naltrexone and acamprosate). Topiramate (TOP), an FDA-approved medication for seizures and migraines, showed moderate effect sizes in achieving abstinence and decreasing craving, when compared to placebo, in a recent meta-analysis. However, TOP therapy did not provide clinical improvement in objective sleep or subjective insomnia. Furthermore, hypnotic medication treatments with trazodone, gabapentin, and ramelteon have shown variable impact for sleep disturbance and abstinence. By contrast, all four studies evaluating Cognitive Behavioral Therapy for Insomnia (CBT-I) have shown a large magnitude of effect for treating insomnia but with minimal to no effect on abstinence. Thus, combining TOP and CBT-I will strengthen their recovery and improve their overall functioning. This combination treatment will be the first personalized intervention in treating Veterans with AUD and comorbid insomnia. A sample of treatment-seeking Veterans with AUD (N=174) will be initially treated with TOP 200 mg a day for six weeks, and then randomized to receive either CBT-I (N=87) or Sleep Hygiene Education (SHE, a behavioral placebo intervention) (N=87) weekly for the next eight weeks. We will conduct CBT-I following our standard protocol using 30-minute sessions to deliver its components (Sleep Restriction, Stimulus Control, Sleep Hygiene and Cognitive Therapy). A post-intervention visit will be conducted eight weeks after the intervention phase. The primary outcome measure will be the Percent Days Abstinent (as computed from the Time Line Follow Back interview) and the insomnia severity (as assessed using the Insomnia Severity Index). Also, we will track other aspects of alcohol use, sleep and daily functioning using TLFB, PACS, sleep diaries, BDI, and the STAI to test whether successful treatment of drinking and insomnia will be associated with better clinical outcomes in AUD. It is hypothesized that in Veterans with AUD, the combination of TOP+CBT-I, as compared to TOP+SHE group, will lead to 1) a more significant percentage of days abstinent from alcohol, and 2) superior sleep-related outcomes along with pre-post treatment effect sizes comparable to the meta-analytic norms. If these hypotheses are supported, the findings will need to be validated in a larger multi-center trial. If validated, the findings would support: 1) including insomnia treatment as a standard component of the initial protocol for treating AUD comorbid with insomnia, and 2) using TOP+CBT-I combination treatment to manage this subpopulation of AUD patients.