Clinical Efficacy of Lisdexamfetamine for Methamphetamine Dependence

描述（由申请人提供）：本申请是对题为“探索性发展研究资助计划”的PA-11-261的重新提交。对甲基苯丙胺（冰毒）的依赖具有严重的不良医疗、社会和社会后果。很少有研究调查了治疗这种疾病的潜在药物，包括缓解冰毒戒断症状的药物的疗效。药物开发也受到了阻碍，因为通常采用的研究设计是检查戒断的开始，而不是预防复发。早期戒断通常与戒断症状和重新使用冰毒有关。一种有希望的治疗方法是使用间接激动剂药物治疗甲基苯丙胺依赖；然而，研究很少，而且在方法上有相当大的差异。尽管激动剂治疗对其他药物（包括兴奋剂尼古丁）的依赖取得了成功，但由于几个原因，包括长期接触安非他明可能导致滥用、精神病和神经毒性影响，人们不愿更仔细地检查激动剂治疗对兴奋剂依赖的效果。因此，考虑到使用短期激动剂治疗减轻戒断的潜力，本提案将研究激动剂利地氨苯他明（LDX）在以下方面的功效：1)延迟复发时间；2)减轻最近戒断的甲基苯丙胺依赖个体的戒断症状。这项为期9周、随机、双盲、安慰剂对照的临床试验将在两年的时间内为40名甲基苯丙胺依赖者（18-65岁）提供治疗。参与者首先将住在一个住宅设施（阿肯色州的康复中心）进行启动

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.