Evaluation Of Treatments Of Opioid And Cocaine Dependence

我们已经证明了行为干预的有效性（可卡因阴性尿样的强化）在大的市中心静脉注射多种药物滥用者的样本，我们将继续评估应用治疗的最佳方法。 为了研究奖金为基础的禁欲强化，海洛因/可卡因使用者（N=116）美沙酮维持（100毫克/天）的影响，随机分配到一个非偶然的控制组（NonC）或三个组之一，赢得奖品抽奖禁欲：手动绘图与标准奖金密度（MS），或计算机绘图与标准（CS）或高（CH）密度。 概率（奖品/抽奖）为：标准50%，高78%;奖品密度是双盲的。 平均奖金为：CH $286; CS $167; MS $139; NonC $171。 结果是12周干预期间和干预后8周阿片类药物/可卡因阴性尿液的百分比以及研究后6个月内的依赖诊断。 干预期间CH组的阴性标本显著多于NonC组，干预后治疗组的阴性标本显著多于所有组：根据基线药物使用和脱落校正的干预后治疗组的平均阴性%（95%置信区间）为：CH 55%（14-90%）; CS 7%（1-27%）; MS 4%（1-12%）; NonC：3%（1-10%）。 目前可卡因依赖诊断治疗后显着降低，在特遣队相比，noncontingent组。 电脑绘图与高密度的奖品加强减少可卡因的使用;禁欲强化有长期的治疗效益。 与禁欲强化相关的主要挑战是其可能的高昂成本和工作人员/资源密集度，特别是当强化遵循不断增加的金额计划时。 工作流程的挑战包括满足入选标准的不同条件，分层到不同的组，跟踪选择的候选人类别，以及根据实验室结果或其他方案定义的标准确定奖金候选人的资格。为了应对这些挑战，与NIDA IRP的生物医学信息学部分合作，我们实施了用于禁欲强化的自动应急管理（ACM）决策支持系统。 我们正在继续改进该系统，并制定机制，使其可用于社区治疗方案。 这种系统的可用性将促进技术转让，并增加社区使用循证程序来加强禁欲。 在进一步的技术开发工作中，我们正在探索在患者日常环境中使用手持电子设备进行治疗。 在已经实现禁欲的人中，主要的问题是复发的可能性。 α-激动剂洛非西定可能有助于预防美沙酮维持治疗患者因压力诱发的海洛因使用复发。 然而，这两种药物都表现出心血管和神经认知活动，并且从未报道过同时给药的安全性。 我们研究了洛非西定和美沙酮联合给药对血流动力学和认知功能的影响。 14例美沙酮维持治疗（80 mg/d）患者接受递增剂量的洛非西定（0 - 1.6 mg/d，单盲）治疗8周。 在每次新洛非西定给药的第一天，监测洛非西定和美沙酮联合给药的急性直立性生命体征和神经心理学效应，持续给药后5小时。 此后每天评估直立性生命体征和不良事件（AE），以评估重复给药的影响。 与安慰剂（仅美沙酮）相比，洛非西定降低了坐位收缩压和舒张压（BP）（分别为p=0.045和p=0.033）;在0.4 mg洛非西定时，坐位收缩压和舒张压的平均降低分别为27 ± 17和15 ± 16 mm Hg。 然而，立位体征变化与洛非西定剂量之间无显著相关性。 认知效率降低也与洛非西定给药相关;与安慰剂相比，较高剂量的洛非西定对数学任务的表现有不良影响（p=0.0035）。 不良事件的发生率与剂量无关;大多数事件（64.5%）是洛非西定的常见副作用。 与美沙酮单独给药相比，洛非西定和美沙酮联合给药观察到血流动力学和认知效率的显著变化。 我们的结论是，美沙酮和洛非西定不应同时给予维持治疗，直到进一步的研究解决联合治疗的安全性。

We have already demonstrated the effectiveness of behavioral interventions (reinforcement for cocaine-negative urine samples) in large inner-city samples of intravenous polydrug abusers, and we continue to evaluate the best ways to apply the treatment. To examine the effect of reinforcer density in prize-based abstinence reinforcement, heroin/cocaine users (N=116) in methadone maintenance (100 mg/day) were randomly assigned to a noncontingent control group (NonC) or one of three groups that earned prize draws for abstinence: manual drawing with standard prize density (MS), or computerized drawing with standard (CS) or high (CH) density. Probabilities (prizes/draw) were: standard 50%, high 78%; prize density was double blind. Mean prize values were: CH $286; CS $167; MS $139; NonC $171. Outcomes were % opioid/cocaine-negative urines during the 12-week intervention and 8 weeks post-intervention and diagnosis of dependence up to 6 months post study. CH had significantly more negative specimens than NonC during intervention and more than all groups during post-intervention treatment: mean % negative (95% confidence interval) during post-intervention treatment adjusted for baseline drug use and dropout were: CH 55% (14-90%); CS 7% (1-27%); MS 4% (1-12%); NonC: 3% (1-10%). Current cocaine-dependence diagnoses after treatment were significantly lower in contingent compared to noncontingent groups. Computerized drawing with higher-density prizes enhanced reduction of cocaine use; abstinence reinforcement had long-term therapeutic benefits. The major challenge associated with abstinence reinforcement is its likely prohibitive cost and staff/resource intensity, especially when the reinforcement follows an escalating amount schedule. Workflow challenges include varying conditions for meeting inclusion criteria, stratification into various groups, tracking categories of reinforcers chosen, and determination of eligibility for bonus reinforcers based on laboratory results or other protocol-defined criteria. To address these challenges, in collaboration with the Biomedical Informatics Section of the NIDA IRP, we implemented the Automated Contingency Management (ACM) decision support system for abstinence reinforcement. We are continuing to improve the system and to develop mechanisms to make it available to community treatment programs. The availability of such a system would promote technology transfer and increase community use of evidence-based procedures for abstinence reinforcement. In further technology development work, we are exploring the use of handheld electronic devices for treatment delivery in patients daily environment. In individuals who have achieved abstinence, the main concern is the likelihood of relapse. The alpha-agonist lofexidine may help prevent stress-induced relapse to heroin use in patients on methadone maintenance. Both agents, however, exhibit cardiovascular and neurocognitive activities, and the safety of simultaneous administration has never been reported. We examined the hemodynamic and cognitive effects of lofexidine and methadone coadministration. Fourteen patients in methadone maintenance (80 mg/d) received escalating doses of lofexidine (0 to 1.6 mg/d, single blind) for up to 8 weeks. Acute orthostatic vital signs and neuropsychological effects of lofexidine and methadone co-administration were monitored for five hours post-dose on the first day of each new lofexidine dose. Orthostatic vital signs and adverse events (AEs) were assessed daily thereafter to assess effects of repeated dosing. Lofexidine decreased sitting systolic and diastolic blood pressure (BP) (p=0.045 and p=0.033 respectively) compared to placebo (methadone alone); at 0.4 mg lofexidine, the mean decreases in sitting systolic and diastolic BP were 27+17 and 15+16 mm Hg respectively. There was, however, no significant association between changes in orthostatic vitals and lofexidine dose. Decreased cognitive efficiency was also associated with lofexidine administration; higher lofexidine doses adversely affected performance on a mathematical task relative to placebo (p=0.0035). Adverse event incidence was not dose dependent; the majority of events (64.5%) were common side effects of lofexidine. Significant changes in hemodynamic and cognitive efficiency were observed with coadministration of lofexidine and methadone compared to methadone alone. We concluded that methadone and lofexidine should not be administered concomitantly in maintenance treatment until further studies address the safety of combination therapy.