Clinical Efficacy of Atomoxetine for Methamphetamine Dependence

托莫西汀治疗甲基苯丙胺依赖的临床疗效

• 批准号: 8306734
• 负责人: Alison Oliveto
• 金额: $ 22.13万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8306734
• 关键词: Abstinence; Agonist; Amphetamines; Area; Arkansas; Attention deficit hyperactivity disorder; Attenuated; Blood Pressure; Bulla; Childhood; Clinical Trials; Cocaine Abuse; Cocaine Dependence; Cognitive Therapy; Controlled Clinical Trials; Data; Dependence; Development; Diagnosis; Disease; Dopamine; Double-Blind Method; Drug Addiction; Drug abuse; Equilibrium; Exposure to; Future; Goals; HIV; Home environment; Incentives; Individual; Intervention; Length; Light; Medical; Methamphetamine; Methamphetamine dependence; Methodology; Monitor; Morbidity - disease rate; Nature; Neurotransmitters; Norepinephrine; Outcome; Outpatients; Participant; Patient Self-Report; Patients; Performance; Pharmaceutical Preparations; Pharmacotherapy; Placebo Control; Placebos; Play; Process; Psychostimulant dependence; Psychotic Disorders; Public Health; Randomized; Recovery; Relapse; Relative (related person); Research; Research Design; Research Project Grants; Residential Facilities; Risk; Role; Sampling; Schedule; Severities; Societies; Substance abuse problem; Symptoms; Therapeutic; Time; Toxicology; Treatment outcome; Urine; Visit; Withdrawal; Withdrawal Symptom; addiction; atomoxetine; base; clinical efficacy; clinical practice; cognitive function; design; discounting; drug abstinence; improved; inhibitor/antagonist; minimal risk; mortality; neurotoxic; noradrenergic; prevent; prognostic; programs; psychosocial; psychostimulant; reboxetine; response; reuptake; sex; social; treatment program; treatment response; volunteer

DESCRIPTION (provided by applicant): This application is a resubmission in response to PA-10-069, 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. Recent evidence suggests that norepinephrine plays a more important role in the addiction process than previously thought, particularly in relapse as well as the expression of psychostimulant withdrawal. A promising therapeutic approach involves the use of indirect agonist pharmacotherapy for METH dependence; however, there are a limited number of studies and considerable variability in methodology. Despite successful agonist treatments for dependence on other drugs, there has been a reluctance to examine more closely agonist treatment for stimulant dependence for several reasons. Thus, given that recent evidence suggests agents that alter noradrenergic activity may be effective in treating drug dependence, this application will examine the efficacy of the selective noradrenergic reuptake inhibiter atomoxetine in 1) delaying time to relapse and 2) alleviating withdrawal symptoms in recently abstinent METH-dependent individuals. This 11-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 atomoxetine (80 mg/day; N=20). Then participants transfer to the Outpatient Treatment Research Program and continue to receive study medication for weeks 3-10. 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 10 weeks, patients will be taken off the study medication, monitored during week 11, and referred to an appropriate treatment program. Efficacy will be determined by length of time in treatment, alleviation of withdrawal symptoms, length of time to lapse/relapse as determined by urine toxicology, and psychosocial functioning. The findings of this trial, if positive, will support an R01 application to examine the efficacy of atomoxetine 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.

描述（由申请人提供）：本申请是对PA-10-069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。最近的证据表明，去甲肾上腺素在成瘾过程中起着比以前认为的更重要的作用，特别是在复发以及精神兴奋剂戒断的表达。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，研究数量有限，方法学存在相当大的差异。尽管成功的激动剂治疗对其他药物的依赖，一直不愿意更密切地检查激动剂治疗兴奋剂依赖的几个原因。因此，鉴于最近的证据表明改变去甲肾上腺素能活性的药物可能有效治疗药物依赖，本申请将检查选择性去甲肾上腺素能再摄取抑制剂托莫西汀在最近戒断的MET依赖性个体中1）延迟复发时间和2）缓解戒断症状的疗效。这项为期11周、随机、双盲、安慰剂对照的临床试验将为40名METH依赖者（18-65岁）提供为期两年的治疗。受试者首先将居住在住宅机构（阿肯色州的康复中心），开始初始药物戒断并接受研究药物治疗。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）或托莫西汀（80 mg/天; N=20）。然后，参与者转入门诊治疗研究项目，并继续接受研究药物治疗3-10周。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10周结束时，患者将停用研究药物，在第11周期间进行监测，并接受适当的治疗方案。疗效将通过治疗时间长度、戒断症状缓解、通过尿液毒理学确定的至失效/复发时间长度和心理社会功能来确定。如果该试验的结果为阳性，则将支持R 01应用，以在更大样本中检查托莫西汀的疗效和各种因素的预后相关性。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。