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

摘要

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.