Transcranial Magnetic Stimulation for the Treatment of Veterans with Alcohol Use Disorders

本研究的目的是评价重复经颅磁刺激(Rtms)的疗效。 作为对患有酒精使用障碍(AUD)的退伍军人的治疗，以降低极高的 与这种情况相关的复发。 至少60%的AUD患者将在治疗后6个月内经历一段严重的复发期， 无论采取何种干预措施(心理和/或药理学)。因此，最高 退伍军人AUD和治疗后复发的患病率与大量资源相关 DVA医疗保健系统的分配和费用。当前的药理学和心理社会干预 仅表现出中等水平的疗效，这反映在AUD的高复发率上。 RTMS是一种神经刺激方法，处于创新、非侵入性和安全治疗的前沿 对于AUD，以及通常与AUD共同发生的疾病。降低退伍军人的高复发率 对于AUD，有必要进行干预，以更有效地解决相关的神经生物学问题 功能障碍和显著的共生状况。因此，额外的严格控制的研究是 需要确定rTMS是否是治疗退伍军人AUD的有效方法。 参与者将从退伍军人事务部帕洛阿尔托医疗保健系统(VAPAHCS)住宅区招募 虐待治疗诊所一项双盲随机临床试验，分为两组：主动rTMS治疗组 (活动性rTMS)-将接受每周四至五次治疗(每天两次)，为期两周。假的 对照组(即相同的rTMS实验程序，但没有主动刺激)将接受 RTMS会话的频率和持续时间相同。建议的rTMS方案与FDA一致 VAPAHCS MIRECC批准的治疗方案用于治疗严重的抑郁障碍。磁性 磁共振成像(MR)将在rTMS治疗前完成，并用于定位每个患者的左侧DLPFC 学员将针对该地区优化RTMS。活动和假rTMS组将完成预测性措施 [即前额叶谷氨酸：谷氨酰胺比率(GLX)、血流量和组织容量的MR测量] 开始rTMS治疗(基线)和其他结果衡量标准(即渴望、情绪、焦虑的衡量标准) 在为期两周的rTMS会议结束前和结束后立即进行。基线前部的测量 额叶GLX、血流水平和组织体积是建立预测的潜在生物标志物所必需的 RTMS治疗反应，这是治疗优化所必需的。接下来的6个月 完成积极或虚假的rTMS治疗后，将每月通过电话或 完成酒精和物质使用以及渴求的简单标准化测量，以评估 了解这些变量在过去30天内的变化。 该项目将在第一个月提供关于rTMS对患有AUD的退伍军人的疗效的全新数据 治疗后6个月。在治疗后的整个前6个月内进行监测至关重要，因为 在治疗的前6个月内复发与较差的心理社会功能有关。 随之而来的1-3年。这项提议最终目标是提供更有效地促进 患有AUD的退伍军人中的持续戒酒，因为延长戒酒与最佳戒酒密切相关 生物医学、神经心理学、精神病学和心理社会康复和功能。

The purpose of this study is to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) as a treatment for Veterans with an alcohol use disorder (AUD) to decrease the exceedingly high rate of relapse associated with this condition. At least 60% of those with AUD will experience a major relapse period within 6 months of treatment, irrespective of the intervention (psychosocial and/or pharmacological) employed. Consequently, the high prevalence of AUD and relapse following treatment in Veterans is associated with substantial resource allocation and costs for the DVA Health Care System. Current pharmacological and psychosocial interventions demonstrate only a moderate level of efficacy, which is reflected in the high rate of relapse in AUD. rTMS is a neurostimulation method that is at the forefront of innovative, non-invasive, and safe treatments for AUD, and the disorders that commonly co-occur with AUD. To reduce the high rate of relapse in Veterans with AUD, it is necessary for interventions to more effectively address the associated neurobiological dysfunction and salient co-occurring conditions. Accordingly, additional rigorously controlled studies are required to determine if rTMS is an effective treatment for Veterans with AUD. Participants will be recruited from VA Palo Alto Health Care System (VAPAHCS) residential substance abuse treatment clinics A double-blind randomized clinical trial with two groups: Active rTMS Treatment Group (Active rTMS) – will receive four to five treatments (two treatments per day) each week for 2 weeks. Sham Control Treatment group (i.e., identical rTMS experimental procedure, but no active stimulation) will receive the same frequency and duration of rTMS sessions. The proposed rTMS protocol is consistent with the FDA approved treatment regimen employed for major depressive disorders at the VAPAHCS MIRECC. Magnetic resonance imaging (MR) will be completed prior to rTMS treatment and used to localize the left DLPFC in each participant to optimize rTMS for this region. Active and Sham rTMS groups will complete predictive measures [i.e., MR measures of anterior frontal glutamate:glutamine ratio (Glx), blood flow and tissue volume] prior to the inception of rTMS treatment (baseline) and other outcome measures (i.e., measures of craving, mood, anxiety) immediately pre- and post-completion of the 2 weeks of rTMS sessions. Measurement of baseline anterior frontal Glx, blood flow levels, and tissue volumes is necessary to establish potential biomarkers for prediction of rTMS treatment response, which is requisite for therapeutic optimization. For the 6 months following completion of active or sham rTMS treatment, participants will be contacted monthly, via telephone or in person, to complete a brief standardized measure of alcohol and substance use, as well as craving, to assess for changes in these variables over the previous 30 days. This project will deliver completely novel data on the efficacy of rTMS for Veterans with AUD during the first 6 months following treatment. Monitoring over the entire first 6 months following treatment is crucial, given relapse within the first 6 months of treatment is robustly related to poor psychosocial functioning over the ensuing 1-3 years. The ultimate goal of this proposal is provide treatment that more effectively promotes sustained abstinence in the Veteran with AUD, as extended abstinence is robustly associated with optimum biomedical, neuropsychological, psychiatric, and psychosocial recovery and functioning.