New Approaches to Cocaine Abuse Medications

可卡因滥用药物的新方法

• 批准号: 7628364
• 负责人: Edward V. Nunes
• 金额: $ 39.26万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7628364
• 关键词: Abstinence; Achievement; Address; Alcohol or Other Drugs use; Anhedonia; Antidepressive Agents; Behavior Therapy; Behavioral; Brain; Clinical; Clinical Trials; Cocaine; Cocaine Abuse; Cocaine Dependence; Cognitive; Cognitive Therapy; Communities; Congresses; DSM-IV; Depressed mood; Depressive Syndromes; Depressive disorder; Desipramine; Diagnosis; Disease; Double-Blind Method; Drug usage; Failure; General Population; Healthcare Systems; High Prevalence; Hospitalization; Hospitals; Incentives; Intervention; Major Depressive Disorder; Medical; Mental Depression; Mental disorders; Methods; Moods; Outcome; Outpatients; Patients; Pharmaceutical Preparations; Pharmacotherapy; Placebos; Procedures; Public Health; Randomized; Rate; Reinforcement Schedule; Reporting; Research; Research Personnel; Rewards; Sampling; Schedule; Shapes; Subgroup; Substance Use Disorder; System; Treatment Protocols; United States; United States Substance Abuse and Mental Health Services Administration; Week; Withdrawal; Work; base; cost; depressive symptoms; design; disorder later incidence prevention; follow-up; improved; neurochemistry; novel strategies; placebo controlled study; problem drinker; psychosocial; reinforcer; response; social; success; tool; treatment effect; venlafaxine; voucher; week trial

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.

描述（由申请人提供）： 可卡因依赖仍然是美国的一个主要社会和医疗问题。有效的行为疗法已经被开发出来，但失败率仍然很高，需要有效的药物疗法。大多数药物开发工作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（例如同时患有抑郁症的患者）上，可以获得更大的成功。抑郁症在可卡因依赖患者中普遍存在，并与不良预后相关。在本项目下，在选定的抑郁症可卡因滥用者中进行了抗抑郁药物地昔帕明的安慰剂对照试验，取得了令人鼓舞的结果，抑郁症状对地昔帕明治疗有反应，并且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，而且很少有患者能够戒除。临床智慧以及在酗酒者中进行的相关试验结果表明，当在医院戒酒一段时间后可以诊断出抑郁症时，药物治疗效果最强，因此代表原发性抑郁症，而不是物质引起的抑郁症。然而，这种住院治疗在大多数情况下并不切合实际，而且临床医生缺乏在门诊快速建立戒断的工具。此外，在现在提出的试验中，可卡因依赖门诊患者会见，通过将药物与戒断优惠券激励相结合，可以增强抗抑郁药物的影响，特别是对可卡因使用的影响。 目前重度抑郁症的DSM-IV标准，将首先进入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，根据最初的戒断诱导程序后抑郁症是否有所改善，对患者进行分层，并随机分配至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计划，继续获得根据禁欲情况而定的代金券。将解决以下具体目标： 具体目标#1：确定患有抑郁症的可卡因依赖患者中的文拉法辛在改善抑郁症和可卡因使用方面是否优于安慰剂。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酒初期抑郁症持续存在的患者。