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

认知行为疗法 (CBT-I) 增强托吡酯促进酒精使用障碍 (AUD) 戒酒的作用。

• 批准号: 10394786
• 负责人: Subhajit Chakravorty
• 金额: --
• 依托单位: PHILADELPHIA VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2025-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10394786
• 关键词: Abstinence; Aftercare; Alcohol consumption; Alcohols; Anxiety; Back; Beck depression inventory; Behavior Therapy; Behavioral; Caring; Clinical; Cognitive Therapy; Communities; Comorbid Insomnia; Development; Disulfiram; Education; Epilepsy; Equipment and supply inventories; Exhibits; FDA approved; General Population; Guidelines; Heavy Drinking; Hygiene; Impairment; Individual; Intervention; Interview; Measures; Meta-Analysis; Migraine; Multicenter Trials; Naltrexone; Outcome; Outcome Measure; Pathologic; Patients; Pharmaceutical Preparations; Phase; Placebo Control; Placebos; Prevalence; Protocols documentation; Quality of life; Randomized; Recovery; Relapse; Reporting; Risk; Sampling; Seizures; Severities; Sleep; Sleep disturbances; Sleeplessness; Stimulus; Suicide; Testing; Time; TimeLine; Titrations; Trazodone; Veterans; Visit; acamprosate; actigraphy; affective disturbance; alcohol abstinence; alcohol abuse therapy; alcohol comorbidity; alcohol craving; alcohol use disorder; arm; comorbidity; craving; daily functioning; design; diaries; dosage; drinking; drinking behavior; follow-up; gabapentin; high risk; hypnotic; improved; indexing; innovation; off-label drug; personalized intervention; post intervention; prevent; primary outcome; recidivism; relapse risk; side effect; sleep health; sobriety; suicidal behavior; suicidal risk; topiramate; trait; treatment effect; treatment guidelines; validation studies

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.

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AUD患者失眠的发生率是普通人群的3-9倍，但 合并AUD和失眠的AUD严重程度更高，酒精渴望增加，质量降低 早期自杀行为和复发的风险较高， 禁欲由于副作用，治疗饮酒行为和失眠的选择有限 （双硫仑）或仅对饮酒结果产生适度影响（纳洛酮和阿坎酸）。托吡酯（TOP）， FDA批准的用于癫痫发作和偏头痛的药物，在实现禁欲方面显示出中等的效果 在最近的一项荟萃分析中，与安慰剂相比，然而，TOP疗法并没有 提供客观睡眠或主观失眠的临床改善。此外，催眠药物 用曲唑酮、加巴喷丁和雷美替酮治疗显示出对睡眠障碍的不同影响， 禁欲相比之下，所有四项评估认知行为疗法（CBT-I）的研究都 对治疗失眠有很大的效果，但对禁欲的效果很小甚至没有。因此，在本发明中， 将TOP和CBT-I合并将加强其恢复并改善其整体运作。这 联合治疗将是治疗患有AUD和合并症的退伍军人的第一个个性化干预措施。 失眠 一名寻求治疗的AUD退伍军人样本（N=174）最初将接受TOP200 mg a治疗 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），持续接下来的8周。我们将根据我们的 标准协议使用30分钟的会话来提供其组件（睡眠限制，刺激控制， 睡眠卫生与认知疗法（Sleep Hygiene and Cognitive Therapy）干预后访视将在干预后8周进行。 干预阶段。主要结局指标将是禁欲天数百分比（根据 时间线随访访谈）和失眠严重程度（使用失眠严重程度指数评估）。 此外，我们还将使用TLFB、PACS、睡眠日记， BDI和STAI测试是否成功治疗饮酒和失眠将与更好的 以AUD表示的临床结局。假设在患有AUD的退伍军人中，TOP+CBT-I的组合，如 与TOP+SHE组相比，将导致1）更显著的戒酒天数百分比，以及 2)上级睡眠相关结局沿着，治疗前后效应量与荟萃分析相当 规范高效如果这些假设得到支持，则需要在更大的多中心试验中验证这些发现。如果 经过验证，研究结果将支持：1）将失眠治疗作为初始治疗的标准组成部分， 治疗AUD合并失眠的方案，和2）使用TOP+CBT-I联合治疗来管理 这一亚群的AUD患者。