Sertraline Augmentation for Cocaine Dependence

在我们之前的中心，SSR[单独使用舍曲林并与多巴胺再摄取一起增强]的疗效 研究对象是最近戒毒的可卡因滥用者。初步调查结果如下 与安慰剂相比，舍曲林中出现可卡因阳性尿液的可能性显著降低 单独和舍曲林-丁丙酮组，这种作用在舍曲林的整个试验中没有持续 独自一人组。在这项提案中，将探讨舍曲林单独使用和舍曲林增强的疗效。 进一步使用具有GABA能活性的药物，基于证据表明GABA能活性，在 除了多巴胺和5-羟色胺能活性外，还可能在治疗可卡因依赖患者方面发挥作用， 尤其是那些同时患有抑郁症的人。例如，GABA的增加与减少有关 在抑郁症状方面，我们有初步数据显示，一种GABA能药物在促进 美沙酮稳定的可卡因滥用患者的可卡因戒断情况。因此，本项目将研究 舍曲林单独及与GABA转运体抑制剂替加宾联合应用的临床疗效 或者在抑郁的可卡因滥用者中使用伽巴喷丁。这12周，双盲，随机 临床试验将为140名抑郁、依赖可卡因的人(18-65岁)提供治疗，时间超过五年- 一年期间。参与者首先将住在退伍军人事务部医疗系统的一个住院病房里，开始 最初的可卡因戒断，根据抑郁症状的严重程度和 舍曲林转运体，并被分配接受以下一种药物：安慰剂，舍曲林(200INE/天)， 舍曲林加替加他滨(12毫克/天)，或舍曲林+加巴喷丁(1200毫克/天)。然后参与者转移 参加门诊治疗研究计划，并继续接受为期3-12周的学习药物治疗。 在试验的门诊部分，受试者每周参与个人认知行为 接受治疗，并因遵守研究要求而获得金钱奖励。12周后， 患者将逐渐停止研究药物治疗，并转介到适当的治疗计划。功效 将由治疗时间长短、复发时间长短、自我报告和尿液决定 毒理学、抑郁症状严重程度和心理社会功能。这些因素与预后的相关性 抑郁症状的严重程度、性别、催乳素水平、例如舍曲林的遗传多态、 多纳明。和GARA转运体，以及对经颅磁刺激的反应。

n our previous center, the efficacy of the SSR[ sertraline alone and augmented with the dopamine-reuptake inhibitor bupropionin depressed, recently-abstinent cocaine abusers was examined. Preliminary findings are that the likelihood of cocaine-positive urines was significantly decreased relative to placebo in the sertraline alone and sertraline-bupropiongroups, an effect that was not sustained for the entire trial in,the sertraline alone group. In this proposal, the efficacy of sertraline alone and sertraline augmentation will be explored further using agents with GABAergic activity, based on evidence suggesting that GABAergic activity, in addition to dopaminergic and serotonergic activity, may play a role in treating cocaine dependent patients, particularly those with concurrent depression. For instance, increases in GABA are associated with decreases in depressive symptoms and we have preliminarydata showing efficacy of a GABAergic agent infacilitating cocaine abstinence in cocaine-abusing methadone-stabilized patients. Thus, this project will examine the clinical efficacy of sertraline alone and in combination with either the GABA transporter inhibitor tiagabine or the GABAergic agent gabapentin in depressed cocaine abusers. This 12-wk, double-blind, randomized clinical trial will provide treatment for 140depressed, cocaine-dependent individuals (18-65 yrs) over a five- year period. Participants first will reside in a residential ward at the VA CT Healthcare System to initiate initial cocaine abstinence, be randomized by depressive symptom severity and genetic polymorphism at the sertraline transporter, and be assigned to receive one of the following: placebo, sertraline (200 ing/day), sertraline plus tiagabine (12 mg/day), or sertraline plus gabapentin (1200mg/day). Then participants transfer to the OutpatientTreatment Research Program and continue to receive study medication for weeks3-12. During the outpatient portion of the trial, subjects participate in weekly individual cognitive behavioral therapy and are given monetary incentives for complying with study requirements. At the end of 12 weeks, patients will be tapered off the study medication and referred to an appropriate treatment program. Efficacy will be determined by length of time in treatment, length of time to relapse, by self-report and urine toxicology, depressive symptom severity and psychosocial functioning. Prognostic relevance of factors such as depressive symptom severity, sex,prolactin levels, genetic polymorphisms at the, e.g., sertraline, donamine. and GARA transporters, and response to transcranial magnetic stimulation will he examined.