Combined Pharmacotherapies for Cocaine Dependence

描述(由申请人提供)：可卡因使用障碍在美国仍然是一个严重的公共卫生问题。尽管目前还没有FDA批准的可卡因使用障碍的药物疗法，但一些候选药物的研究已经产生了令人振奋的结果。鉴于近年来在开发治疗酒精、阿片和尼古丁使用障碍的有效药物疗法方面取得的成功，开发治疗可卡因使用障碍的有效药物疗法仍然是一个重要的公共卫生目标。物质使用障碍药物治疗的一个最新研究趋势是测试具有不同机制的药物组合，以评估它们的协同效应潜力。在这一系列研究中最重要的努力之一是NIAAA资助的纳曲酮和氨基己酸酯治疗酒精依赖的联合研究。具有不同作用机制的多种药物的组合很早就被精神病学和其他医学专业的临床实践所接受。然而，可卡因使用障碍药物治疗的临床试验几乎完全测试了单一药物的给药。因此，我们建议将两种在治疗可卡因使用障碍方面显示出希望的不同作用机制的药物结合起来，以确定联合治疗是否比安慰剂更有效。拟议的项目是一项随机、双盲、安慰剂对照的缓释混合苯丙胺盐(ER-MAS)联合托吡酯治疗可卡因依赖的试验。符合DSM-IV可卡因依赖标准的门诊患者将进入为期一周的安慰剂引导试验，然后进入为期12周的前瞻性、平行组、随机、安慰剂对照试验。本研究的具体目的如下：1.探讨ER-MAS和托吡酯在促进可卡因依赖患者戒断中的作用。2.探讨ER-MAS和托吡酯对可卡因依赖患者戒断症状的影响。3.探索一系列相关的次要结果(治疗保留、全球功能和艾滋病毒危险行为)以及可能反映行动机制的调节因素和中介因素。

DESCRIPTION (provided by applicant): Cocaine-use disorders continue to be a significant public health problem in the US. Although there are no FDA-approved pharmacotherapies for cocaine use disorders, some studies of candidate medications have yielded promising results. Given the success in recent years in developing effective pharmacotherapies for alcohol, opioid, and nicotine use disorders, the development of effective pharmacotherapies for cocaine use disorders remains an important public health goal. A recent research trend in substance-use disorder pharmacotherapy is the testing of combinations of agents with different mechanisms to evaluate their potential for synergistic effects. One of the most significant efforts in this line of research is the NIAAA- funded COMBINE Study of naltrexone and acamprosate in the treatment of alcohol dependence. The combination of multiple medications with distinct mechanisms of action has long been accepted into clinical practice in psychiatry and other medical specialties. However, cocaine use disorder pharmacotherapy clinical trials have almost exclusively tested the administration of a single agent. Therefore, we are proposing combining two agents with distinct mechanisms of action that have shown promise in the treatment of cocaine use disorders to determine if the combined therapy is more effective than placebo. The proposed project is a randomized double-blind placebo-controlled trial of extended-release mixed amphetamine salts (ER-MAS) combined with topiramate for the treatment of cocaine dependence. Outpatients meeting DSM-IV criteria for cocaine dependence will enter a one-week placebo lead-in followed by a 12-week prospective, parallel group, randomized, placebo-controlled trial. Following are the specific aims of this study: 1. To determine the efficacy of ER-MAS and topiramate in promoting cocaine abstinence among cocaine- dependent patients. 2. To determine the effect of ER-MAS and topiramate on cocaine craving among cocaine-dependent patients. 3. To explore a set of related secondary outcomes (treatment retention, global functioning, and HIV risk behavior) as well as moderators and mediators potentially reflective of mechanism of action.