New Approaches to Cocaine Abuse Medications

描述(由申请人提供)： 在美国，对可卡因的依赖仍然是一个主要的社会和医疗问题。已经开发了有效的行为疗法，但失败率仍然很高，需要有效的药物疗法。大多数开发药物的努力一般都是针对可卡因依赖的。这项建议寻求另一种方法，即通过将治疗重点放在特定的亚群上，例如共生抑郁症患者，将获得更大的成功。抑郁症在可卡因依赖患者中很普遍，并与不良结局相关。根据该项目，在选定的抑郁可卡因滥用者中进行了一项抗抑郁药物地昔帕明的安慰剂对照试验，结果令人鼓舞，抑郁症状对地昔帕明治疗有反应，抑郁的改善与可卡因使用量的减少相关。然而，药物对可卡因使用的直接影响并不能被证明，而且很少有患者实现戒断。临床智慧和对酗酒者的相关试验结果表明，当在医院持续戒酒一段时间后能够被诊断为抑郁症时，药物效果最强，因此代表了一种原发抑郁症，而不是物质诱导的抑郁症。然而，在大多数情况下，这样的住院治疗是不现实的，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，特别是对可卡因使用的影响，可以通过结合药物和凭单激励来加强，取决于禁欲，在现在提议的试验中，可卡因依赖的门诊患者，会议 目前严重抑郁症的DSM-IV标准将首先进入14天的禁欲诱导期，并采用旨在诱导初步禁欲的高价值代金券激励方案。然后，患者将根据他们的抑郁是否在最初的禁欲诱导程序中得到改善而进行分层，并随机分配到抗抑郁药物文拉法辛或安慰剂，进行为期12周的双盲试验。在试验期间，他们将根据为在社区治疗环境中实施而制定的低成本间歇性增援计划，继续获得视戒毒情况而定的代金券。将讨论以下具体目标：具体目标1：确定可卡因依赖抑郁障碍患者在凭证激励方面是否优于安慰剂，以改善抑郁和可卡因使用。具体目标2：确定文拉法辛对抑郁和可卡因使用结果的影响是否仅限于在凭单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.