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

摘要 酒精使用障碍(AUD)是一个昂贵且负担沉重的健康问题，影响着超过1500万成年人 每年在美国。FDA批准的几种药物辅助疗法(MAT)用于 治疗AUD，用双硫兰(安非他命)最古老，也是最常见的之一。双硫兰作为一种 “心理威慑”，与酒精一起服用时会引起生理反应。尽管展示了 减少复发的疗效，双硫兰未得到充分利用：在监测或治疗的情况下证明效果最佳 监督，为使用制造障碍。此外，双硫兰的依从率很低。最常见的 不坚持的原因是个人正在考虑或计划复发，这种情况通常会发生 在50小时内。因此，双硫兰不依从性可以作为复发的标志，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：设备被设计成 客观跟踪遵守情况。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，通过触发短信(SMS)进行时间监控。Wisepill设备加药物 提醒短信与更多地坚持抗逆转录病毒或糖尿病治疗有关。尽管 这种能力是存在的，潜在的治疗性短信与Wisepill客观监测相结合还没有 在任何人群中进行测试。事实上，以前的研究表明，支持性和复发性预防/应对 技能短信干预在减少饮酒方面是有效的。因此，鉴于二硫氰胺- 坚持可以表示一个关键的临床问题(即，即将复发)，即提供量身定制的复发 在停用双硫兰后不久，以预防为重点的及时短信可能会对 AUD治疗结果。我们建议开发一种利用Wisepill技术进行配对的干预 使用定制的(A)实时触发提醒、(B)实时禁欲的实时药物监测 支持，以及(C)预防复发短信短信，适用于使用二硫氰胺治疗的澳门氏症患者。 我们建议为酒精治疗的个体开发为期12周的Wisepill短信干预 双硫仑。这将包括：1)面对面的Wisepill培训会议，介绍该设备并生成 量身定做的预防复发信息；2)在强化治疗计划期间使用Wisepill设备以及 出院后；3)配合使用Wisepill设备的定制短信：a)支持短信 服药依从性，b)早期不遵守的提醒消息(例如，延迟1小时)和c)复发- 在较长的不遵守时间段(例如，几个小时)后的预防消息。此应用程序的目标是 是在焦点小组(n=20)的帮助下开发Wisepill短信干预，然后测试Wisepill短信 RCT中的干预(n=75)，将Wisepill SMS与仅Wisepill(即，无SMS)和仅双硫仑作比较(即， 没有Wisepill，没有短信)。Wisepill设备及其相关的实时监测和消息传递系统， 成本相对较低，易于编程，并且可以提供干预措施，减少护理障碍。

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.