Memantine Naltrexone Treatment for Opioid Dependence

描述(申请人提供)：在过去几年中，新吸食海洛因的人数和与吸食海洛因有关的问题稳步增加。美沙酮维持治疗是目前治疗阿片类药物依赖最有效的方法，但它具有局限性，并存在争议。另一种药理策略，纳曲酮维持，目前由于依从性差和患者可接受性低而用处有限。改进的治疗方法，包括新的药物以及纳曲酮的药理和行为增强策略是非常必要的。 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依赖。这些化合物抑制药物条件反应，在实验动物中发挥复发作用，减少阿片类药物的自我给药，并减轻阿片类药物的戒断。在人类中，NMDA受体拮抗剂可以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求的主观影响。这项为期五年的研究的目标是测试美金刚(一种非竞争性NMDA受体拮抗剂)作为纳曲酮维持治疗的辅助药物在戒毒海洛因依赖者中的疗效。 在拟议的试验中，165名完成脱毒的海洛因依赖患者将被随机分配到三种情况之一(1)纳曲酮+安慰剂；(2)纳曲酮+美金刚30毫克，2次；和(3)纳曲酮+美金刚60毫克，2次(每组55人)。纳曲酮将在诊所每周配药三次，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，其中包括激励性访谈和认知行为预防复发。心理社会干预的目标是改善服药依从性并保持禁欲。双盲试验将持续12周，评估以基线为基准，每个预约每周三次。重复评估也将在治疗结束后一个月、两个月和三个月完成。主要结果指标将是在研究结束时继续接受治疗，以及在研究结束前的最后四周内戒除海洛因。主要目的是测试美金刚在纳曲酮维持的阿片依赖患者中减少早期磨耗和改善结局的有效性。

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.