A targeted, real-time, technology-supported intervention for patients with alcohol use disorder on disulfiram

摘要 酒精使用障碍（AUDs）是一个昂贵和负担沉重的健康问题，影响超过1500万成年人 每年在美国。几种FDA批准的药物辅助治疗（MAT）用于 治疗AUD，双硫仑（Antabuse）是最古老也是最常见的。双硫仑作为一种 “心理威慑”，并导致生理反应时，采取与酒精。尽管很多矿业公司表示 减少复发的疗效，双硫仑未得到充分利用：疗效最好在监测或 监管，形成使用壁垒。此外，双硫仑依从率较低。最常见的 不依从的原因是个体正在考虑或计划复发， 在50小时内。因此，双硫仑非依从性可以是复发的标志物，为复发提供了非常短的窗口。 干预技术进步现在允许电子药物监测：设备被设计为 客观地跟踪依从性。Wisepill设备是一种电子药物监测系统，它将真实的- 当剂量延迟时，通过触发的文本消息（SMS）进行时间监测。Wisepill设备加上药物 提醒SMS消息与抗逆转录病毒或糖尿病治疗的依从性增加相关。虽然 这种能力是存在的，潜在的治疗SMS消息与Wisepill客观监测配对， 在任何人群中进行测试。事实上，以前的研究表明，支持性和复发预防/应对 短信干预措施在减少酒精使用方面是有效的。因此，鉴于双硫氨非- 依从性可能意味着严重的临床问题（即，即将复发），提供量身定制的复发 在双硫仑停药后不久，以预防为重点的及时短信可能会对 AUD治疗结局。我们建议开发一种利用Wisepill技术的干预措施， 实时药物监测，具有定制的（a）实时触发提醒，（B）实时禁欲 支持，和（c）复发预防短信的个人与AUD正在接受disulfram治疗。 我们建议为酒精治疗的个人开发一个为期12周的Wisepill+SMS干预， 双硫仑这将包括：1）亲自参加WisePill定向会议，介绍器械并生成 量身定制的复发预防信息; 2）在强化治疗计划期间使用Wisepill设备， 出院后; 3）与Wisepill设备的使用配对的定制SMS消息：a）支持消息， 药物依从性，B）早期不依从的提醒消息（例如，1小时后）和c）复发- 在较长时间的不遵守之后的预防消息（例如，几个小时）。这个应用程序的目标是 是在焦点小组（n=20）的帮助下开发Wisepill+SMS干预，然后测试Wisepill+SMS 干预RCT（n=75）比较Wisepill+SMS与仅Wisepill（即，无SMS）和仅双硫仑（即， 没有Wisepill，没有SMS）。Wisepill设备及其相关的实时监控和消息传递系统， 成本相对较低，易于编程，并且可以提供减少护理障碍的干预措施。

ABSTRACT Alcohol use disorders (AUDs) are a costly and burdensome health concern, affecting over 15 million adults each year in the United States. Several FDA-approved medication-assisted therapies (MATs) are used for the treatment of AUD, with disulfiram (Antabuse) the oldest and one of the most common. Disulfiram acts as a “psychological deterrent” and causes physiological reactions when taken with alcohol. Despite demonstrated efficacy for decreasing relapse, disulfiram is underutilized: efficacy is best demonstrated under monitoring or supervision, creating a barrier for use. Additionally, disulfiram adherence rates are low. The most common reason for non-adherence is that an individual is contemplating or planning a relapse, which typically occurs within 50 hours. Thus, disulfiram non-adherence can be a marker for relapse, providing a very short window for intervention. Technological advances now allow for electronic medication monitoring: devices are designed to objectively track adherence. The Wisepill device is an electronic medication monitoring system that pairs real- time monitoring with a triggered text message (SMS) when doses are late. The Wisepill device plus medication reminder SMS messages are associated with increased adherence to antiretroviral or diabetic therapy. Though the capability exists, potentially therapeutic SMS messages paired with Wisepill objective monitoring have yet to tested in any population. Indeed, previous research suggests that supportive and relapse prevention/coping skills SMS message interventions are effective in reducing alcohol use. Thus, given that disulfram non- adherence can signify a critical clinical concern (i.e., impending relapse), the delivery of a tailored, relapse prevention-focused, just-in-time SMS soon after disulfiram discontinuation could have a significant impact on AUD treatment outcomes. We propose to develop an intervention capitalizing on the Wisepill technology to pair real-time medication monitoring with tailored (a) real-time triggered reminders, (b) real-time abstinence support, and (c) relapse prevention SMS texts for individuals with AUD being treated with disulfram. We propose to develop a 12-week Wisepill+SMS intervention for individuals in alcohol treatment on disulfiram. This will include: 1) an in-person Wisepill orientation session to introduce the device and generate tailored relapse prevention messages; 2) use of the Wisepill device during the intensive treatment program and after discharge; 3) tailored SMS messages paired with use of the Wisepill device: a) supportive messages with medication compliance, b) reminder messages for early non-adherence (e.g., 1 hour late) and c) relapse- prevention messages after longer periods of non-adherence (e.g., several hours). The goal of this application is to develop the Wisepill+SMS intervention with the aid of focus groups (n=20), then test the Wisepill+SMS intervention in a RCT (n=75) comparing Wisepill+SMS to Wisepill only (i.e., no SMS) and disulfiram only (i.e., no Wisepill, no SMS). The Wisepill device, and its associated real-time monitoring and messaging systems, are relatively low-cost, easy to program, and can deliver an intervention that would reduce barriers to care.