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: 9788210
• 负责人: Michael Lloyd Perlis
• 金额: $ 69.62万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9788210
• 关键词: Address; Adverse event; Agonist; Behavioral; Benzodiazepine Receptor; Chronic Insomnia; Clinical; Cognitive Therapy; Comorbidity; DSM-V; Disease; Dose; Elderly; Exhibits; Frequencies; General Population; Goals; Half-Life; 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; Regimen; Relapse; Rest; Risk Factors; Safety; Severities; Sleep; Sleeplessness; Symptoms; Time; Treatment Protocols; conditioning; cost; experimental group; habituation; hazard; hypnotic; improved; pill; primary outcome; side effect; targeted treatment; treatment choice; treatment effect; treatment responders; treatment response; zolpidem

Three Approaches to Maintenance Therapy for Chronic Insomnia in Older Adults ABSTRACT Insomnia is nearly twice as common among older adults as it is 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 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. While CBT-I is the treatment of choice, the medical treatment of insomnia remains the primary alternative for those for whom CBT-I is not indicated, preferable, or available. 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 in the context of maintenance therapy (over the course of years or decades). In the case of intermittent dosing (IDS), the reduced usage approach is thought to extend the efficacy and safety “half-life” of pharmacotherapy, but at a cost: little or no treatment effects on non-medication nights. In order to address this issue, we have proposed that behavioral principles be applied to pharmacotherapy to determine whether clinical gains obtained with standard therapy can be maintained with partial reinforcement (nightly pill use where some of the pills contain zolpidem and some are placebos). Building upon the findings from our prior study with partial reinforcement, we propose to assess a low frequency approach to dosing as compared to nightly medication use in older adults. The study will be conducted in three phases. In Phase 1, all subjects receive 5mg zolpidem nightly for one month and are assessed for treatment response. In Phase 2, treatment responders will be 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 and the rest placebos); or a low frequency IDS condition (1 to 3 active doses per week). 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, number and severity of medical symptoms function during treatment, and daytime function 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.

老年人慢性炎症维持治疗的三种方法 摘要 在老年人中，Increased几乎是普通人群的两倍。这一点意义重大 临床关注，因为失眠是新发和复发精神病和内科疾病的危险因素。采取 总之，老年人失眠的患病率和后果表明， 未经治疗。这种临床必要性进一步强调了1）在 DSM-5和ICSD-3作为一种疾病（与其他疾病的症状相比）和2）靶向治疗的发现 睡眠连续性障碍可能会产生临床收益的医疗和精神疾病， 与失眠症并存因此，目前的问题不是是否治疗，而是如何最好地治疗。 一般情况下，特别是在老年人的情况下。虽然CBT-I是治疗的选择， 失眠症的药物治疗仍然是那些不适合CBT-I的人的主要选择， 更可取的，或可用的。在现有的医学治疗方法中，研究得最好的策略是苯二氮卓类药物 和苯二氮卓受体激动剂（BZRA）。在这两种情况下，治疗通常是完成与 夜间或间歇给药。在夜间给药（QHS）的情况下，已发现BZRA是安全的， 有效期长达一年。不太清楚的是，这种功效是否可以在 维持治疗（几年或几十年）。在间歇给药（IDS）的情况下， 减少使用的方法被认为可以延长药物治疗的有效性和安全性“半衰期”，但 费用：在非药物治疗的夜晚，治疗效果很小或没有。为了解决这个问题，我们建议 行为原则应用于药物治疗，以确定是否获得临床收益， 标准治疗可以通过部分强化（夜间使用药丸，其中一些药丸含有 唑吡坦和一些是安慰剂）。基于我们先前部分强化研究的发现， 我们建议在老年人中评估与每晚用药相比的低频给药方法， 成年人了研究将分三个阶段进行。在第1阶段，所有受试者每晚接受5 mg唑吡坦， 一个月，并评估治疗反应。在II期，治疗应答者将被随机分配至 三个月的四种维持条件之一：夜间用药（QHS）;两种低频率之一 部分强化条件（每周1或3次活性剂量，其余为安慰剂）;或低频率IDS 条件（每周1至3次活性剂量）。第三阶段将是一个延长期，在9个月内评估 方法的长期持久性。研究的结果将是：复发率、复发潜伏期， 平均睡眠连续性，治疗期间和白天医学症状功能的数量和严重程度 治疗期间的功能。该研究的主要假设是，部分强化条件将 产生与夜间给药相似的结果和优于IDS条件的上级结果。