Three Approaches to Maintenance Therapy for Chronic Insomnia in Older Adults

老年人慢性失眠维持治疗的三种方法

• 批准号: 9341745
• 负责人: Michael Lloyd Perlis
• 金额: $ 80.53万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9341745
• 关键词: Accounting; Address; Adverse effects; Adverse event; Age; Agonist; Behavioral; Benzodiazepine Receptor; Benzodiazepines; Case Management; Chronic Disease; Chronic Insomnia; Clinical; Cognitive Therapy; Conditioned Stimulus; Data; Dependence; Diagnostic and Statistical Manual of Mental Disorders; Disease; Dose; Elderly; Exhibits; Expectancy; Frequencies; General Population; Half-Life; Health; Incidence; Individual; Investigation; Maintenance; Maintenance Therapy; Measures; Medical; Mental disorders; Morbidity - disease rate; Outcome; Outcome Study; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phase; Placebos; Prevalence; Psychological Dependence; Psychological reinforcement; Randomized; Recurrence; Relapse; Risk; Risk Factors; Safety; Severities; Sleep; Sleeplessness; Symptoms; Temazepam; Therapeutic; Time; Treatment Cost; base; capsule; clinical effect; conditioning; cost; habituation; hazard; hypnotic; improved; interest; pill; primary outcome; sleeping pill; targeted treatment; treatment choice; treatment responders; treatment response; zolpidem

 DESCRIPTION (provided by applicant): Insomnia is nearly twice as common among older adults as it is in the general population. This is of significant clinical concern as insomnia is a risk factor for new onset and recurrent psychiatric and medical illness. Taken together, the prevalence and consequences of insomnia in older adults suggests that insomnia should not go untreated. This potential clinical imperative is further underscored by 1) the reconceptualization of Insomnia within the DSM-5 and ICSD-3 as a disorder (vs. a symptom of other disorders) and 2) the findings that targeted treatment of sleep continuity disturbance may produce clinical gains for medical and psychiatric disorders that occur comorbidly with insomnia. Thus, at present, the question is not whether to treat but how to best treat the disorder in general, and specifically in the context of older adults. Of the available medical treatments, the best studied strategies are benzodiazepines and benzodiazepine receptor agonists (BZRAs). In both cases, treatment is typically accomplished with either nightly or intermittent dosing. In the case of nightly dosing (QHS), BZRAs have been found to be safe and efficacious for periods of up to a year. Less clear is whether such efficacy can be maintained over the course of years or decades. In the case of intermittent dosing (IDS), the reduced usage strategy is thought to extend the efficacy and safety "half-life" of pharmacotherapy, but at a cost: little or no clinical effects on non-medication nights. In order to address this issue, we propose to evaluate an alternative approach that is based on the behavioral principles of conditioning and reinforcement. Specifically, we propose to garner treatment responses with full dose treatment (1 month) and then conduct maintenance therapy using intermittent dosing with placebos on non-medication nights. This approach, by expectancy alone, should provide for better clinical outcomes than standard intermittent dosing. What makes the study theoretically interesting is the underlying concept: that the initial treatment response allows for the medication vehicle (the capsule) to become a conditioned stimulus for the therapeutic response (sleepiness and sleep) and that this can be maintained over time (if not indefinitely) with partial reinforcement. Building upon the findings from our prior investigation with partial reinforcement, we propose to assess two low frequency approaches to maintenance therapy in a three phase study. In Phase 1, all subjects receive zolpidem nightly for one month and are assessed for treatment response. In Phase 2, responders are randomized to one of four maintenance conditions for three months: Nightly medication use (QHS); one of two low frequency partial reinforcement conditions (1 or 3 active doses per week with placebos on non-medication nights); and a low frequency IDS condition (1 to 3 active doses per week, without placebos). Phase 3 will be an extension period to assess, over 9 months, the long-term durability of the approaches. The outcomes for the study will be: rate of relapse, latency to relapse, average sleep continuity, and number and severity of medical symptoms during treatment. The primary hypothesis for the study is that the partial reinforcement conditions will produce similar outcomes to nightly dosing and superior outcomes to the IDS condition.

 描述（通过应用程序提供）：失眠几乎是老年人中常见的两倍。这是重要的临床问题，因为失眠是 新发作和经常性精神病和医学疾病的危险因素。综上所述，老年人失眠的患病率和后果表明失眠不应接受。 1）DSM-5和ICSD-3内的失眠症的重新概念化为疾病（与其他疾病的症状）和2）针对睡眠连续性障碍有关的发现可能会导致与Insomynia合并的医学和精神疾病。目前，问题不是要治疗是否治疗，而是如何最好地治疗该疾病，特别是在 老年人的背景。在可用的医疗治疗中，最好的研讨会是苯二氮卓类药物和苯二氮卓受体激动剂（BZRAS）。在这两种情况下，通常通过每晚或间歇性给药完成治疗。就夜间剂量（QHS）而言，已发现BZRA在长达一年的时间内安全有效。不清楚的是，这种有效性在数年或几十年中是否可以维持。间歇性剂量（ID）的情况下，使用降低的使用策略被认为可以扩展药物治疗的有效性和安全性“半衰期”，但要付出一定的代价：对非药物夜晚的临床影响很小或没有临床影响。为了解决这个问题，我们建议评估一种基于调节和加强行为原则的替代方法。具体而言，我们建议通过全剂量治疗（1个月）获得治疗反应，然后在非饮食之夜使用安慰剂进行间歇性剂量进行维持治疗。仅根据期望，这种方法应与标准间歇剂量相比，应提供更好的临床结果。使研究理论上有趣的是基本概念：最初的治疗反应允许药物（胶囊）成为治疗反应（嗜睡和睡眠）的条件刺激，并且可以随着时间的推移（如果不是绝对地）进行部分加强。在我们先前对部分强化调查的发现的基础上，我们建议在三阶段研究中评估两种低频维持治疗方法。在第1阶段，所有受试者每晚每晚接受唑吡坦，并评估治疗反应。在第2阶段，响应者在三个月内随机分配到四个维护条件之一：使用夜间药物（QHS）；两种低频部分加固条件之一（在非药物晚上，安慰剂每周1或3个活跃剂量）；和低频ID条件（每周1至3个活性剂量，无安慰剂）。第3阶段将是评估9个月以上方法的长期耐用性的延长期。该研究的结果将是：救济率，继电器的潜伏期，平均睡眠连续性以及治疗过程中医疗症状的数量和严重程度。该研究的主要假设是，部分加强条件将产生与IDS条件的夜间剂量和卓越结果相似的结果。