Evaluation Of Treatments Of Opioid And Cocaine Dependence

我们已经在市中心静脉注射多药滥用者的大样本中证明了行为干预(加强可卡因阴性尿样)的有效性，并继续评估应用这种治疗的最佳方法。为了考察强化剂密度在奖赏戒断强化中的作用，将116名接受美沙酮维持(100 mg/d)的海洛因/可卡因吸毒者随机分配到非条件控制组(NONC)或因戒毒而获得奖品抽奖的三组中的一组：标准奖品密度(MS)的手工抽奖，或标准(CS)或高密度(CH)的计算机绘图。概率(奖品/抽签)为：标准50%，高78%；奖品密度为双盲。平均奖金为：286澳元、167澳元、139澳元、171澳元。结果是干预12周期间和干预后8周的阿片类药物/可卡因阴性尿量的百分比，以及研究后6个月内被诊断为依赖。干预期间CH的阴性样本显著多于非C组，干预后治疗期间CH的平均%阴性(95%可信区间)为：CH55%(14-90%)；CS 7%(1-27%)；MS 4%(1-12%)；Non-C：3%(1-10%)。与非意外事件组相比，意外事件组治疗后目前被诊断为可卡因依赖的患者显著减少。使用高密度奖品的计算机绘图增强了可卡因使用的减少；戒酒强化具有长期的治疗益处。 与加强戒酒相关的主要挑战是其可能令人望而却步的成本和工作人员/资源强度，特别是当加强遵循不断增加的数额时间表时。工作流程面临的挑战包括满足纳入标准的不同条件、分成不同的组、跟踪所选增强剂的类别，以及根据实验室结果或其他议定书定义的标准确定奖励增强剂的资格。为了应对这些挑战，我们与NIDA IRP的生物医学信息学部门合作，实施了用于加强禁欲的自动应急管理(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计划。这一系统的提供将促进技术转让，并增加社区对加强禁欲的循证程序的使用。在进一步的技术开发工作中，我们正在探索在患者的日常环境中使用手持电子设备进行治疗。 在已经实现禁欲的个人中，主要担心的是复发的可能性。阿尔法激动剂洛非西定可能有助于防止美沙酮维持患者因应激而再次使用海洛因。然而，这两种药物都表现出心血管和神经认知活动，同时给药的安全性从未报道过。我们检测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例美沙酮维持组(80 mg/d)接受剂量递增的洛非西定(0~1.6 mg/d，单盲)治疗，疗程长达8周。在每个新剂量的第一天监测洛非西定和美沙酮联合给药后5小时的急性立位生命体征和神经心理效应。此后每天评估立位生命体征和不良事件(AEs)，以评估重复给药的效果。与安慰剂(单独服用美沙酮)相比，洛非西定降低了坐位血压(BP)(分别为p=0.045和p=0.033)；当洛非西定为0.4 mg时，坐位收缩压和舒张压的平均降幅分别为27±17和15±16毫米汞柱。然而，立位生命体征的改变与洛非西定剂量之间没有明显的关联。认知效率降低也与服用洛非西定有关；与安慰剂相比，较高的洛非西定剂量会对数学任务的表现产生不利影响(p=0.0035)。不良事件发生率与剂量无关；大多数事件(64.5%)是洛非西定常见的副作用。与单用美沙酮相比，联合应用洛非西定和美沙酮可显著改善血流动力学和认知效率。我们的结论是，在进一步的研究解决联合治疗的安全性之前，美沙酮和洛非西定不应同时用于维持治疗。

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.