New Approaches to Cocaine Abuse Medications

描述（由申请人提供）： 在美国，可卡因依赖仍然是一个主要的社会和医学问题。有效的行为疗法已经开发出来，但失败率仍然很高，需要有效的药物治疗。大多数开发药物的努力都是针对一般的可卡因依赖。该提案寻求另一种方法，即通过将治疗重点放在特定亚组（如合并抑郁症的患者）上，可以取得更大的成功。抑郁症在可卡因依赖患者中普遍存在，并与不良结局相关。在该项目下进行的抗抑郁药物地昔帕明在选定的抑郁可卡因滥用者中的安慰剂对照试验产生了令人鼓舞的结果，即抑郁症状对地昔帕明治疗有反应，抑郁症的改善与可卡因使用的减少相关。然而，药物对可卡因使用的直接影响无法得到证实，很少有患者实现戒断。临床智慧和酗酒者中相关试验的结果表明，当抑郁症在医院禁欲一段时间后被诊断出来时，药物效果最强，因此代表了原发性而不是物质诱导的抑郁症。然而，这种住院治疗在大多数情况下是不切实际的，临床医生缺乏在门诊基础上快速建立禁欲的工具。此外，抗抑郁药物的影响，特别是对可卡因的使用，可能会加强药物与代金券奖励视禁欲，在试验中，现在提出，可卡因依赖门诊病人，会议 目前符合DSM-IV标准的重性抑郁症，将首先进入为期14天的戒断诱导期，采用高价值代金券激励方案诱导初始戒断。然后，患者将根据他们的抑郁症是否在最初的戒断诱导程序中得到改善进行分层，并随机分配到抗抑郁药物文拉法辛或安慰剂组，进行为期12周的双盲试验。在试验期间，他们将继续根据为在社区治疗环境中实施而制定的低成本间歇性强化时间表，根据禁欲情况获得代金券。具体目标1：确定在可卡因依赖抑郁症患者中，文拉法辛在代金券激励的背景下在改善抑郁症和可卡因使用方面是否上级安慰剂。具体目标#2：确定文拉法辛对抑郁症和可卡因使用结果的影响是否仅限于在代金券激励支持的戒断初期抑郁持续的患者。

DESCRIPTION (provided by applicant): Cocaine dependence continues to represent a major social and medical problem in the United States. Effective behavioral therapies have been developed, but failure rates remain high, and effective pharmacotherapies are needed. Most efforts to develop medications have targeted cocaine dependence in general. This proposal pursues an alternative approach, that greater success would be achieved by focusing treatment on specific subgroups, such as patients with co-occurring depression. Depression is prevalent among cocaine dependent patients and associated with poor outcome. A placebo-controlled trial of the antidepressant medication, desipramine, in selected depressed cocaine abusers, conducted under this Project, yielded encouraging results in that depressive symptoms responded to desipramine treatment, and depression improvement was correlated with reduction in cocaine use. However, a direct effect of medication on cocaine use could not be demonstrated, and few patients achieved abstinence. Clinical wisdom, and the results of related trials among alcoholics, suggest medication effects are strongest when depression can be diagnosed after persisting during a period of abstinence in hospital, thus representing a primary rather than a substance-induced depression. However, such hospitalization is not practical in most instances, and clinicians have lacked tools for rapidly establishing abstinence on an outpatient basis. Further, the impact of antidepressant medication, particularly on cocaine use, might be enhanced by combining medication with voucher incentives contingent on abstinence, in the trial now proposed, cocaine dependent outpatients, meeting DSM-IV criteria for current major depression, will first enter an abstinence-induction period of 14days, with a high value voucher incentive regimen designed to induce initial abstinence. Patients will then be stratified according to whether their depression improves in response to the initial abstinence-induction procedure, and randomly assigned to the antidepressant medication venlafaxine, or placebo, for a 12-week double-blind trial. During the trial they will continue to receive vouchers contingent on abstinence according to a low cost intermittent reinforcement schedule developed for implementation in community treatment settings. The following specific aims will be addressed: Specific Aim #1: To determine in cocaine dependent patients with depressive disorders whether venlafaxine in the context of voucher incentives is superior to placebo in improving depression and cocaine use. Specific Aim #2: To determine whether the effect of venlafaxine on depression and cocaine use outcome is restricted to patients whose depression persists during an initial period of abstinence supported by voucher incentives.