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

摘要 酒精使用障碍 (AUD) 是一种代价高昂且繁重的健康问题，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 对于 AUD 的治疗，双硫仑（Antabuse）是最古老也是最常见的治疗方法之一。双硫仑的作用是 “心理威慑”，与酒精一起服用时会引起生理反应。尽管已证明 双硫仑在减少复发方面的功效尚未得到充分利用：在监测或 监管，形成使用障碍。此外，双硫仑的依从率很低。最常见的 不遵守的原因是个人正在考虑或计划复发，这通常会发生 50小时内。因此，双硫仑不依从可能是复发的标志，为复发提供了非常短的窗口期。 干预。技术进步现在允许电子药物监测：设备旨在 客观地跟踪遵守情况。 Wisepill 设备是一种电子药物监测系统，可将真实的药物配对 当剂量延迟时，通过触发短信 (SMS) 进行时间监控。 Wisepill 装置加药物 提醒短信与提高抗逆转录病毒或糖尿病治疗的依从性有关。虽然 这种能力是存在的，但尚未与 Wisepill 客观监测相结合，具有潜在治疗作用的 SMS 消息 在任何人群中进行测试。事实上，之前的研究表明，支持性和复发预防/应对 技能 短信干预可有效减少饮酒。因此，考虑到双硫仑非 依从性可能意味着严重的临床问题（即即将复发），需要提供量身定制的复发治疗方案 在双硫仑停用后不久，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 技术的干预措施来配对 实时药物监测，并定制 (a) 实时触发提醒，(b) 实时禁欲 支持，以及 (c) 为接受双硫仑治疗的 AUD 患者提供预防复发短信。 我们建议为接受酒精治疗的个人制定为期 12 周的 Wisepill SMS 干预措施 双硫仑。这将包括：1) 面对面的 Wisepill 指导会议，介绍设备并生成 量身定制的预防复发信息； 2) 在强化治疗计划期间使用 Wisepill 装置以及 after discharge; 3) 与 Wisepill 设备配合使用的定制 SMS 消息： a) 支持消息 药物依从性，b) 早期不依从的提醒信息（例如，迟到 1 小时）和 c) 复发- 较长时间不遵守规定（例如几个小时）后的预防信息。此应用程序的目标 是在焦点小组 (n=20) 的帮助下制定 Wisepill SMS 干预措施，然后测试 Wisepill SMS 在随机对照试验 (n=75) 中进行干预，将 Wisepill SMS 与仅 Wisepill（即无 SMS）和仅双硫仑（即， no Wisepill, no 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.