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

基本信息

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
项目类别：
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

项目摘要

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（由申请人提供）：失眠在老年人中的发病率几乎是普通人群的两倍，这是一个重要的临床问题，因为失眠是一种常见的疾病。总而言之，老年人失眠的患病率和后果表明，失眠不应该得到治疗，这一潜在的临床必要性进一步强调了：1）失眠的重新概念。 5 和 ICSD-3 作为一种疾病（相对于其他疾病的症状），以及 2) 研究结果表明，睡眠连续性障碍的针对性治疗可能会对与以下疾病共存的医学和精神疾病产生临床收益：因此，目前的问题不是是否治疗，而是如何最好地治疗这种疾病，特别是在失眠方面。在现有的药物治疗中，研究最好的策略是苯二氮卓类药物和苯二氮卓类受体激动剂（BZRA），在这两种情况下，通常通过夜间给药或间歇给药（QHS）来完成治疗。已发现 BZRA 的安全性和有效性长达一年，但尚不清楚这种功效是否可以维持数年或数十年。间歇性给药（IDS）的减少使用策略被认为可以延长药物治疗的功效和安全性“半衰期”，但代价是：在非药物治疗夜晚几乎没有或没有临床效果。我们建议评估一种基于调节和强化行为原则的替代方法，具体来说，我们建议通过全剂量治疗（1 个月）来吸引治疗反应，然后在非药物夜晚使用安慰剂间歇给药进行维持治疗。。这仅从预期来看，这种方法应该能提供比标准间歇给药更好的临床结果。从理论上讲，该研究的有趣之处在于其基本概念：初始治疗反应允许药物载体（胶囊）成为治疗的条件刺激。反应（嗜睡和睡眠），并且可以通过部分强化随着时间的推移（如果不是无限期地）维持这种反应。根据我们之前通过部分强化进行的调查结果，我们建议在三个阶段中评估两种低频维持治疗方法。在第一阶段，所有受试者每晚接受唑吡坦治疗一个月，并评估治疗反应。在第 2 阶段，有反应者被随机分配到四种维持条件之一，为期三个月：夜间用药 (QHS)；两种低频部分强化条件之一（1 或 1 种）。每周 3 次活性剂量，在非用药之夜服用安慰剂）；以及低频率 IDS 状况（每周 1 至 3 次活性剂量，不含安慰剂），第 3 阶段将是一个延长期，用于评估 9 个月以上的情况。研究的结果将是：复发率、复发潜伏期、平均睡眠连续性以及治疗期间医学症状的数量和严重程度。将产生与夜间给药类似的结果，并产生优于 IDS 情况的结果。