Prevention of Relapse in Addiction

本节的一个主要举措是通过使用生态瞬时评估（EMA）来研究暴露于假定的复发触发因素（如环境线索和压力）的作用。 我们正在使用美沙酮维持的海洛因/可卡因门诊患者和体重维持计划中的肥胖个体中进行研究。 参与者携带电子日记，记录暴露于假定复发触发因素的基本比率以及复发期间这些触发因素的存在。 在第一个完成的研究中，我们前瞻性地监测了对可卡因和海洛因的渴望和使用的急性日常生活沉淀物。 在一项队列设计中，114名美沙酮维持可卡因和海洛因滥用门诊患者在手持计算机上提供了长达14，918人日的EMA数据（每位参与者平均130.9天，范围6-189）。 在这114例患者中，共有102例患者提供了急性预渴求或使用前数据，因此被纳入本分析。 在每次自我报告的药物渴望或使用事件发生前5小时内，情绪报告和暴露于假定药物使用触发器的变化，通过重复测量logistic回归（SAS GLIMMIX宏）进行分析。 吸毒前5个小时的报告显示，看到毒品、提供毒品、想看看如果我吸毒会发生什么、突然被诱惑吸毒、处理10美元或更多、愤怒、担心、被别人批评、不舒服和心情好，但不是无聊或悲伤。药物渴求前5小时的报告显示出不同的模式，例如，悲伤情绪有序增加，但良好情绪没有增加。 这些研究结果证实，滥用多种药物的个人可以在日常环境中使用掌上电脑提供行为数据，这些数据可以揭示有序的模式，包括前瞻性地检测到的渴望和使用的预兆。 我们也在探索在患者的日常环境中使用手持电子设备进行治疗。 此外，我们正在使用手持电子设备，以改善我们的随机临床试验的结果测量。 我们研究的这一方面来自实验室动物数据，表明压力诱导的可卡因寻求和/或海洛因寻求的恢复可以用α-肾上腺素能激动剂可乐定预防，而线索诱导的这种药物寻求的恢复可以用阿立哌唑预防。 我们正在进行两项可乐定的试验，一项是评估它对压力和药物线索的反应，另一项是评估它在预防复发方面的疗效。 我们目前正在进行一项研究，在这项研究中，美沙酮维持门诊患者全天携带手持电脑，以提供对海洛因和可卡因的渴望，药物使用的失误以及推定的失误率的实时数据。 我们已经在我们的人群中证明了这种形式的数据收集的可行性，并将其用于可乐定试验，以确定可乐定的复发预防效果是否特异于复发亚型。 最后，我们完成了与芝加哥大学研究人员的合作，进行了一项两个地点的研究，以调查戒烟吸烟者的渴望时间进程，特别注意潜伏期的可能性，这是一种在临床前研究中观察到的现象，其中渴望随着戒烟时间的增加而增加。数据分析正在进行中，手稿正在编写中。渴望的潜伏期可能有助于解释以前依赖尼古丁、酒精或非法药物的个体长期易复发的原因。

A major initiative for our section is to examine the role of exposure to putative relapse triggers (such as environmental cues and stress) through the use of ecological momentary assessment (EMA). We are conducting studies in heroin/cocaine-using methadone-maintained outpatients and in obese individuals who are in a weight-maintenance program. Participants carry electronic diaries to record the base rates of exposure to putative relapse triggers as well as the presence of these triggers during relapse. In the first completed study, we prospectively monitored the acute daily-life precipitants of craving for, and use of, cocaine and heroin. In a cohort design, 114 methadone-maintained cocaine- and heroin-abusing outpatients provided EMA data on handheld computers for up to 14,918 person-days (mean 130.9 days per participant, range 6-189). Of those 114, a total of 102 provided acute pre-craving or pre-use data and were thus included in the present analyses. Changes in reports of mood and exposure to putative drug-use triggers at random intervals during the five hours preceding each self-reported episode of drug craving or use, analyzed via repeated-measures logistic regression (SAS GLIMMIX macro). The five hours preceding drug use showed orderly increases in reports of Saw Drugs, Offered Drugs, Wanted to see what would happen if I used, Tempted to use out of the blue, Handled $10 or more, Angry, Worried, Criticized by others, Uncomfortable, and Good mood, but not Bored or Sad. The five hours preceding drug craving showed a different pattern of reports, e.g. an orderly increase in Sad but no increase in Good mood. These findings confirm that polydrug-abusing individuals can provide behavioral data in their daily environments using handheld computers, and that those data can reveal orderly patterns, including prospectively detectable harbingers of craving and use. We are also exploring the use of handheld electronic devices for treatment delivery in patients daily environment. In addition, we are using handheld electronic devices to improve outcome measurement in our randomized clinical trials. This aspect of our research derives from laboratory-animal data showing that stress-induced reinstatement of cocaine seeking and/or heroin seeking can be prevented with the alpha-adrenergic agonist clonidine, while cue-induced reinstatement of such drug seeking can be prevented with aripiprazole. We are conducting two trials of clonidine, one to evaluate its effect on response to stress and drug cues, and the second to evaluate its efficacy in relapse prevention. We are currently conducting a study in which methadone-maintained outpatients carry handheld computers throughout the day to provide real-time data on cravings for heroin and cocaine, lapses to drug use, and base rates of putative lapse precipitants. We have demonstrated the feasibility of this form of data collection in our population and are using it in the clonidine trial to determine whether clonidines relapse-prevention effect is specific to subtypes of relapse. Finally, we completed a collaboration with investigators at the University of Chicago on a two-site study to investigate the time course of craving in abstinent smokers, with particular attention to the possibility of incubation, a phenomenon seen in preclinical studies, in which craving increases with duration of abstinence. Data analysis is underway, and a manuscript is in preparation. Incubation of craving may help explain the long-lasting vulnerability to relapse in individuals formerly dependent on nicotine, alcohol, or illicit drugs.