Sertraline Augmentation for Cocaine Dependence

舍曲林增强可卡因依赖性

• 批准号: 7648022
• 负责人: Alison Oliveto
• 金额: $ 32.74万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7648022
• 关键词: Abstinence; Antidepressive Agents; Behavior Therapy; Bupropion; Caring; Cocaine; Cocaine Abuse; Cocaine Dependence; Cognitive Therapy; Controlled Clinical Trials; Depressed mood; Diagnosis; Dopamine; Dopamine Uptake Inhibitors; Double-Blind Method; Ensure; Equilibrium; GABA Agents; GABA transporter; Genetic; Genetic Polymorphism; Healthcare Systems; Incentives; Individual; Length; Measures; Mental Depression; Methadone; Motor; Outpatients; Oxidoreductase; Participant; Patient Self-Report; Patients; Pharmaceutical Preparations; Placebo Control; Placebos; Play; Prognostic Factor; Prolactin; Psychological reinforcement; Randomized; Randomized Clinical Trials; Relapse; Relative (related person); Research; Role; Selective Serotonin Reuptake Inhibitor; Sertraline; Severities; Testing; Time; Toxicology; Transcranial magnetic stimulation; Urine; Week; base; clinical efficacy; day; depressive symptoms; dopamine transporter; gabapentin; gamma-Aminobutyric Acid; inhibitor/antagonist; prognostic; programs; psychosocial; response; serotonin transporter; sex; tiagabine; treatment program; volunteer; ward

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.

在我们之前的中心，单独使用 SSR[舍曲林并通过多巴胺再摄取增强的疗效 对最近戒除可卡因滥用者的抑制剂安非他宁进行了检查。初步调查结果是 与安慰剂相比，舍曲林尿液中可卡因阳性的可能性显着降低 单独使用和舍曲林-安非他酮组使用，这种效果在舍曲林的整个试验中并未持续 单独组。在该提案中，将探讨单独使用舍曲林和舍曲林增强疗法的功效 进一步使用具有 GABA 活性的药物，基于表明 GABA 活性的证据， 除了多巴胺能和血清素能活性外，可能在治疗可卡因依赖患者中发挥作用， 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 在抑郁症状中，我们有初步数据显示 GABA 能药物促进的功效 滥用美沙酮稳定的可卡因患者的可卡因戒断。因此，本项目将审查 舍曲林单独使用以及与 GABA 转运蛋白抑制剂噻加宾联用的临床疗效 或抑郁症可卡因滥用者中的 GABA 能药物加巴喷丁。这个为期 12 周、双盲、随机 临床试验将在五年内为 140 名抑郁症、可卡因依赖者（18-65 岁）提供治疗 年期间。参与者首先将居住在 VA CT 医疗系统的住宅病房，以启动 初始可卡因戒断，根据抑郁症状严重程度和基因多态性进行随机分组 舍曲林转运蛋白，并被指定接受以下其中一项：安慰剂、舍曲林（200 粒/天）、 舍曲林加噻加宾（12 毫克/天），或舍曲林加加巴喷丁（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第 3-12 周的研究药物治疗。 在试验的门诊部分，受试者每周参加一次个人认知行为测试 治疗并因遵守学习要求而获得金钱奖励。 12 周结束时， 患者将逐渐减少研究药物的用量，并转诊至适当的治疗方案。功效 将根据治疗时间长短、复发时间长短、自我报告和尿液来确定 毒理学、抑郁症状严重程度和心理社会功能。诸如此类的因素的预后相关性 如抑郁症状的严重程度、性别、催乳素水平、基因多态性，例如舍曲林、 多纳胺。和 GARA 转运蛋白，以及对经颅磁刺激的反应将被检查。