Novel EtG BasedContingency Management for Alcohol in the Severely Mentally Ill

摘要 这种竞争性延续（续期）申请的目的是确定是否对 应急管理（CM）干预可改善重度饮酒者的结局并降低成本， 严重精神疾病（SMI）。高达46%的成年SMI患者在其一生中经历过酒精使用障碍。 酗酒导致无家可归、精神病住院、艾滋病毒感染、吸烟的比例很高 吸烟和药物使用，CM是一种特别有前途的治疗方法。在CM中，患者 因为表现出戒毒而获得切实的奖励。酒精使用的CM需要生物标志物， 检测饮酒后超过48小时。由于直到2011年才获得此类生物标志物， 最近，很少有研究将CM作为酒精使用障碍的治疗方法。在我们的初始资金中 我们发现，酒精生物标志物乙基葡萄糖醛酸苷（EtG）可以检测饮酒长达5天， 作为CM的随机12周试验的一部分施用。随机接受基于EtG的CM的患者为3次 更有可能提交酒精阴性EtG测试比对照。CM参与者也有较低水平的重 饮酒、使用兴奋剂和吸烟的人比对照组多。然而，CM对参与者无效 平均治疗前EtG水平表明频繁的、近期大量饮酒（EtG > 499 ng/mL）。我们 我建议调查两种策略- a）增加酒精含量或B）加强轻度饮酒 在加强禁欲之前-可以改善重度饮酒者的SMI结果。虽然最初的研究 表明这些策略与耐药药物使用者的治疗结果改善相关， 吸烟者，没有随机试验比较他们，调查他们在酒精使用者或成年人， SMI，研究其相对成本效益，或使用理论 模型因此，我们将比较这两种方法与实施的CM干预的有效性。 重度饮酒者重度精神分裂症的初始资助期。共有400名参与者照常接受治疗， 治疗机构将参加为期4周的诱导期。达到平均EtG >的参与者（n=240） 诱导期内499 ng/mL将随机分配至a）4个月的标准量级 用于提交戒酒EtG样品（EtG < 100 ng/mL）的强化CM（微量CM），B）4个月 提交戒酒EtG样本的高幅度CM（高幅度CM），或c）1个月CM 提交酒精样本表明轻度饮酒（EtG < 500 ng/mL），然后进行3个月的CM， 提交戒酒的EtG样本（Shaping CM）。主要结果将是EtG验证的酒精 在治疗的最后3个月内禁欲（当所有强化都取决于禁欲时），以及 在6个月的随访中。我们还将调查次要结局的组间差异， CM条件的综合经济分析，并确定是否构成NIAAA的变量 成瘾神经临床评估框架在3 CM条件下中度戒酒。

ABSTRACT The objective of this competing continuation (renewal) application is to determine whether modifications to a contingency management (CM) intervention improve outcomes and reduce costs in heavy drinkers with serious mental illness (SMI). Up to 46% of adults with SMI experience an alcohol use disorder in their lifetimes. Alcohol use contributes to high rates of homelessness, psychiatric hospitalization, HIV infection, cigarette smoking, and drug use in this population, for which CM is an especially promising treatment. In CM, patients receive tangible rewards for demonstrating drug abstinence. CM for alcohol use requires a biomarker that can detect alcohol use for more than 48 hours after consumption. As no such biomarker was available until recently, little research has investigated CM as a treatment for alcohol use disorders. In our initial funding period we found that the alcohol biomarker ethyl glucuronide (EtG) can detect drinking for up to 5 days when administered as part of a randomized 12-week trial of CM. Those randomized to EtG-based CM were 3 times more likely to submit alcohol-negative EtG tests than controls. CM participants also had lower levels of heavy drinking, stimulant drug use, and cigarette smoking than controls. However, CM was ineffective for participants with an average pre-treatment EtG level that indicated frequent, recent heavy drinking (EtG > 499 ng/mL). We propose to investigate whether 2 strategies – a) increasing reinforcer magnitude or b) reinforcing light drinking before reinforcing abstinence – can improve outcomes in heavy drinkers with SMI. While initial research indicates that these strategies are associated with improved outcomes in treatment-resistant drug users and cigarette smokers, no randomized trial has compared them, investigated them in alcohol users or adults with SMI, investigated their relative cost-effectiveness, or investigated modifiers of CM efficacy using a theoretical model. Therefore, we will compare the efficacy of these 2 approaches to the CM intervention implemented in the initial funding period in heavy drinkers with SMI. A total of 400 participants receiving treatment as usual at 2 treatment agencies will take part in a 4-week induction period. Participants (n=240) who attain a mean EtG > 499 ng/mL during the induction period will be randomized to either a) 4 months of standard-magnitude reinforcement CM for submitting alcohol-abstinent EtG samples (EtG < 100 ng/mL) (Usual CM), b) 4 months of high-magnitude CM for submitting alcohol-abstinent EtG samples (High-Magnitude CM), or c) 1 month of CM for submitting alcohol samples that indicate light drinking (EtG < 500 ng/mL), followed by 3 months of CM for submitting alcohol-abstinent EtG samples (Shaping CM). The primary outcome will be EtG-verified alcohol abstinence during the last 3 months of treatment (when all reinforcement is contingent on abstinence) and during 6 months of follow-up. We will also investigate group differences in secondary outcomes, conduct a comprehensive economic analysis of CM conditions, and determine whether variables that make up the NIAAA Addictions Neuroclinical Assessment framework moderate alcohol abstinence in the 3 CM conditions.