1/2-Sequenced Therapies for Comorbid and Primary Insomnias

描述（由申请人提供）：慢性失眠是一种普遍的疾病，与医疗费用增加、功能受损和发展为严重精神疾病的风险增加有关。认知行为疗法（CBT）和苯二氮卓类受体激动剂（BzRA）药物是最广泛支持的失眠治疗方法。不幸的是，很少有研究比较CBT和BzRA治疗失眠的药物。先前的失眠治疗研究也受到小范围、高度筛选的研究样本、固定剂量和固定药物治疗策略的限制，这些策略不代表通常的可调节剂量实践、相对较短的随访间隔、依赖自我报告或多导睡眠图（PSG）评估的睡眠参数作为结果，而不是与临床实践更相关的失眠缓解指标。最后，研究还没有测试各种治疗顺序策略对那些最初失眠治疗没有反应的人的好处。这个双场地项目将解决这些限制。这两个研究地点将总共招募320名符合慢性失眠症广泛标准的参与者。参与者将通过临床评估和PSG进行评估，然后随机分配到CBT或唑吡坦（最广泛使用的BzRA）的第一阶段治疗。中央培训的治疗师将根据手动的、灵活的治疗算法来管理CBT和唑吡坦。初步结果将在6周后进行评估，治疗缓解者将在接下来的12个月里接受维持治疗。那些通过一线治疗未能达到失眠缓解的患者将被鼓励接受随机分配的第二次6周药物治疗（唑吡坦或曲唑酮）或行为治疗（标准或量身定制的CBT）。所有参与者将在方案开始后12周，以及在继续其最终治疗的3、6、9和12个月随访时进行重新评估。失眠缓解，定义为失眠严重程度指数得分< 8分，将作为治疗比较的主要结果。次要结果包括睡眠日记和PSG睡眠测量；对睡眠和日间功能的主观评分；不良事件;辍学率;治疗的可接受性。研究目的包括：(1)比较CBT与唑吡坦作为一线治疗对持续失眠缓解的疗效；(2)比较一线治疗不能缓解的患者转换治疗策略和强化治疗策略的疗效；(3)比较有和无精神共病患者对一线和二线治疗的反应；(4)探索选定的生物标志物和性状测量作为治疗结果预测因子的有效性。我们的首要目标是获得有助于PI和CMI管理临床指南发展的新信息。

DESCRIPTION (provided by applicant): Chronic insomnia is a prevalent disorder associated with increased health care costs, impaired functioning, and an increased risk for developing serious psychiatric disorders. Cognitive Behavioral Therapy (CBT) and benzodiazepine receptor agonist (BzRA) medications are the most widely supported approaches for insomnia management. Unfortunately, few studies have compared CBT and BzRA medications for insomnia treatment. Previous insomnia treatment studies also have been limited by small, highly screened study samples, fixed- dose and fixed-agent pharmacotherapy strategies that do not represent usual adjustable dosing practices, relatively short follow-up intervals, and reliance on self-reported or polysomnographically (PSG) assessed sleep parameters as outcomes, rather than on insomnia remission indicators that are more relevant to clinical practice. Finally, studies have yet to test the benefits of various treatment-sequencing strategies for those who do not respond to initial their insomnia therapies. This dual-site project will address these limitations. The two study sites will enroll a total of 320 participants who meet broad criteria for chronic insomnia disorder. Participants will be evaluated with clinical assessments and PSG, then randomly assigned to first-stage therapy with CBT or zolpidem (most widely-prescribed BzRA). Centrally trained therapists will administer CBT and zolpidem according to manualized, albeit flexible, treatment algorithms. Initial outcomes will be assessed after 6 weeks, and treatment remitters will be followed for the next 12 months on maintenance therapy. Those who fail to achieve insomnia remission with first-line therapy will be encouraged to accept random assignment to a second, 6-week, medication (zolpidem or trazodone) or behavioral (standard or tailored CBT) treatment. All participants will be re-evaluated 12 weeks after protocol initiation, and at 3-, 6-, 9-, and 12-month follow-ups while continuing their final treatment. Insomnia remission, defined categorically as a score < 8 on the Insomnia Severity Index, will serve as the primary outcome for treatment comparisons. Secondary outcomes will include sleep diary and PSG sleep measures; subjective ratings of sleep and daytime function; adverse events; dropout rates; and treatment acceptability. Study Aims include: (1) comparing the efficacy of CBT and Zolpidem for producing sustained insomnia remission when used as first line therapies; (2) comparing the efficacy of treatment switching and augmentation strategies for those who fail to remit with first line treatments; (3) comparing the responses of those with and without psychiatric comorbities to first and second line treatments; and (4) exploring the usefulness of selected biomarkers and trait measures as predictors of treatment outcomes. Our over-arching goal is to obtain new information that contributes to the development of clinical guidelines for PI and CMI management. PUBLIC HEALTH RELEVANCE: Chronic insomnia is a widely prevalent health condition associated with increased health care costs, impaired functioning, and significantly increased risk for developing serious psychiatric disorders such as Major Depression. Despite the availability of well-supported pharmacological and cognitive-behavioral insomnia therapies, it remains unclear how these therapies can best be employed to produce insomnia remission. This dual-site trial will examine insomnia remission rates produced by these therapies, when employed individually and in various sequences, to determine optimal insomnia management strategies for those with and without psychiatric comorbidities.