Clinical Efficacy of Lisdexamfetamine for Methamphetamine Dependence

描述（由申请人提供）：本申请是对PA-11-261的重新提交，标题为“探索性发展研究资助计划”。“甲基苯丙胺（METH）依赖具有深刻的不良医疗，社会和社会后果。很少有研究检查了治疗这种疾病的潜在药物，包括缓解METH戒断症状的药物疗效。药物开发也受到了阻碍，一般采用研究设计，检查禁欲的开始，而不是防止复发。早期戒断通常与戒断症状和甲基苯丙胺使用复发有关。一种有前途的治疗方法涉及使用间接激动剂药物治疗METH依赖;然而，研究很少，方法学上有相当大的差异。尽管对包括尼古丁兴奋剂在内的其他药物依赖的激动剂治疗取得了成功，但由于若干原因，包括与长期接触安非他明有关的滥用、精神病和神经毒性作用的可能性，人们不愿意更密切地审查激动剂治疗对兴奋剂依赖的影响。因此，考虑到利用短期激动剂治疗缓解戒断的潜力，本提案将检查激动剂利右苯丙胺（LDX）在1）延迟复发时间和2）缓解最近戒断的MET依赖性个体中的戒断症状方面的疗效。这项为期9周、随机、双盲、安慰剂对照的临床试验将为40例METH依赖性（18-65岁）患者提供治疗。个人在两年的时间里。参与者首先将居住在住宅设施（阿肯色州恢复中心）， 初始药物戒断并开始接受研究药物治疗。他们将按性别、依赖严重程度和ADHD儿童诊断随机接受安慰剂（N=20）或LDX（100 mg/天; N=20）。然后，受试者转入门诊治疗研究项目，继续接受研究药物治疗2-4周，并在第5-6周逐渐停用研究药物。在试验的门诊部分，受试者参加每周一次的个体认知行为治疗。在试验期间，参与者将获得金钱奖励，以遵守研究要求。在9周结束时，患者将接受研究结束评估，并被转诊至适当的治疗方案。将在第13周（研究完成后4周）进行最终评估，以确定长期疗效。疗效将通过治疗时间长度、戒断症状缓解、认知功能变化和通过尿液毒理学测定的至失效/复发时间长度来确定。这项试验的结果，如果是积极的，将支持R 01申请，以审查 LDX的有效性和各种因素在更大样本中的预后相关性。因此，这些发现可能会改变临床实践与开发一种有效的药物治疗METH依赖。

DESCRIPTION (provided by applicant): This application is a resubmission in response to PA-11-261, entitled "Exploratory Developmental Research Grant Program." Methamphetamine (METH) dependence has profound adverse medical, social and societal consequences. A paucity of studies has examined potential medications for treating this disorder, including the efficacy of medications to alleviate METH withdrawal symptoms. Medications development has also been hampered by generally employing study designs that examine the initiation of abstinence, rather preventing relapse. Early abstinence is often associated with withdrawal symptoms and relapse to METH use. A promising therapeutic approach involves the use of indirect agonist pharmacotherapy for METH dependence; however, studies are few and have considerable variability in methodology. Despite successful agonist treatments for dependence on other drugs, including the stimulant nicotine, there has been a reluctance to examine more closely agonist treatment for stimulant dependence for several reasons, including the potential for abuse, psychosis and neurotoxic effects associated with prolonged exposure to amphetamines. Thus, given the potential for alleviating withdrawal utilizing a short term agonist therapy, this proposal will examine the efficacy of the agonist Lisdexamfetamine (LDX) in 1) delaying time to relapse and 2) alleviating withdrawal symptoms in recently abstinent METH-dependent individuals. This 9-wk, randomized, double blind, placebo-controlled clinical trial will provide treatment for 40 METH-dependent (18-65 yrs.) individuals over a two-year period. Participants first will reside at a residential facility (Recovery Centers of Arkansas) to initiate initial drug abstinence and be inducted on the study medication. They will be randomized by sex, severity of dependence and childhood diagnosis of ADHD to receive either placebo (N=20) or LDX (100 mg/day; N=20). Then participants transfer to the Outpatient Treatment Research Program and continue to receive study medication for weeks 2-4 and be tapered off study medication during weeks 5-6. During the outpatient portion of the trial, subjects participate in weekly individual cognitive behavioral therapy. During the trial, participants are given monetary incentives for complying with study requirements. At the end of 9 weeks, patients will have end of study assessments and be referred to an appropriate treatment program. Final assessments to determine longer term efficacy will be obtained at week 13, 4 weeks after study completion. Efficacy will be determined by length of time in treatment, alleviation of withdrawal symptoms, changes in cognitive function, and length of time to lapse/relapse as determined by urine toxicology. The findings of this trial, if positive, will support an R01 application to examine the efficacy of LDX and prognostic relevance of various factors in a larger sample. As such, these findings may shift clinical practice with the development of an efficacious pharmacotherapy for METH dependence.