Memantine Naltrexone Treatment for Opioid Dependence

描述（由申请人提供）：在过去几年中，新的海洛因使用者的数量和与海洛因使用有关的问题稳步增加。美沙酮维持治疗是目前阿片类药物依赖最有效的治疗方法，但它有局限性，并存在争议。另一种药理学策略，纳洛酮维持，由于依从性差和患者可接受性低，目前的有效性有限。非常需要改进的治疗方法，包括新的药物以及纳洛酮的药理学和行为增强策略。 临床前研究和初步临床观察支持使用NMDA受体拮抗剂治疗阿片类药物依赖。这些化合物抑制在复发中起作用的药物条件反应，减少阿片类药物自我给药，并减弱实验室动物中的阿片类药物戒断。在人类中，NMDA受体拮抗剂减少与阿片类药物戒断相关的体征和症状，并减少海洛因和海洛因渴望的主观影响。这项为期五年的研究的目的是测试美金刚（一种非竞争性NMDA受体拮抗剂）作为脱毒海洛因依赖者纳洛酮维持治疗的辅助药物的疗效。 在拟议的试验中，165名完成戒毒的海洛因依赖患者将被随机分配到三种条件之一：（1）纳洛酮+安慰剂;（2）纳洛酮+美金刚30 mg bid，和（3）纳洛酮+美金刚60 mg bid（每组N=55）。纳洛酮将在诊所每周分发三次，而美金刚或安慰剂将在家中服用。此外，患者将接受每周两次的心理社会干预，包括动机访谈和认知行为复发预防。心理社会干预的目标是改善药物依从性和保持禁欲。双盲试验将持续12周，在基线和每次预约时进行评估，每周三次。重复评估也将在治疗结束后1个月、2个月和3个月完成。主要结局指标将是研究结束时的治疗保留率和研究终点前最后四周的海洛因戒断率。主要目的是测试美金刚在减少早期消耗和改善维持在纳洛酮上的阿片类药物依赖个体的结果方面的功效。

DESCRIPTION (provided by applicant): The number of new heroin users and problems associated with heroin use have increased steadily over the past several years. Methadone maintenance is currently the most effective treatment for opioid dependence but it has limitations and is controversial. An alternate pharmacological strategy, naltrexone maintenance, has currently limited usefulness due to poor compliance and low patient acceptability. Improved treatment approaches, including novel medication as well as pharmacological and behavioral augmentation strategies for naltrexone are greatly needed. Preclinical studies and preliminary clinical observations support the use of NMDA receptor antagonists in the treatment of opioid dependence. These compounds inhibit drug-conditioned responses that play a role in relapse, reduce opiate self-administration, and attenuate opiate withdrawal in laboratory animals. In humans, NMDA receptor antagonists reduce signs and symptoms associated with opiate withdrawal, and reduce subjective effects of heroin and heroin craving. The goal of this five-year study is to test the efficacy of memantine (a noncompetitive NMDA receptor antagonist) as an adjunct to the maintenance treatment with naltrexone in detoxified heroin-dependent individuals. In the proposed trial, one hundred and sixty five heroin-dependent patients who completed detoxification will be randomly assigned to one of three conditions (1) Naltrexone + Placebo; (2) Naltrexone + Memantine 30 mg bid, and (3) Naltrexone + Memantine 60 mg bid (N=55 per group). Naltrexone will be dispensed three times per week in the clinic, while memantine or placebo will be taken at home. In addition, patients will receive twice weekly psychosocial intervention that will include motivational interviewing and cognitive-behavioral relapse prevention. The goal of psychosocial intervention is to improve compliance with medication and maintain abstinence. A double-blind trial will last twelve weeks with assessments at baseline and at each appointment three times per week. Repeated assessments will also be completed one, two, and three months following the end of treatment. Primary outcome measures will be retention in treatment by the end of the study and heroin abstinence in the final four weeks prior to study endpoint. The primary aim is to test the efficacy of memantine in reducing early attrition and improving outcome in opioid-dependent individuals maintained on naltrexone.