1/2-Sequenced Therapies for Comorbid and Primary Insomnias

描述（由申请人提供）：慢性失眠是一种常见疾病，与医疗保健费用增加、功能受损和发生严重精神疾病的风险增加相关。认知行为疗法（CBT）和苯二氮卓受体激动剂（BzRA）药物是最广泛支持的失眠管理方法。不幸的是，很少有研究比较CBT和BzRA药物治疗失眠。先前的失眠治疗研究也受到以下因素的限制：小的、高度筛选的研究样本、固定剂量和固定药剂的药物治疗策略（不代表通常的可调整剂量实践）、相对较短的随访间隔以及依赖于自我报告或多导睡眠图（PSG）评估的睡眠参数作为结局，而不是依赖于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对最初的失眠治疗没有反应的人的好处。这一双址项目将解决这些限制。这两个研究中心将招募总共320名符合慢性失眠症广泛标准的参与者。参与者将接受临床评估和PSG评估，然后随机分配到CBT或唑吡坦（最广泛的处方BzRA）的第一阶段治疗。经过集中培训的治疗师将根据手动（尽管灵活）治疗算法给予CBT和唑吡坦。将在6周后评估初始结局，并在接下来的12个月内对治疗缓解者进行维持治疗随访。对于一线治疗未能达到失眠缓解的患者，将鼓励他们接受随机分配，接受第二次为期6周的药物（唑吡坦或曲唑酮）或行为（标准或定制CBT）治疗。所有受试者将在方案启动后12周以及3个月、6个月、9个月和12个月随访时重新评估，同时继续接受最终治疗。炎症缓解，分类定义为炎症严重程度指数评分< 8，将作为治疗比较的主要结局。次要结局将包括睡眠日记和PSG睡眠测量;睡眠和日间功能的主观评分;不良事件;脱落率;和治疗可接受性。研究目的包括：（1）比较CBT和唑吡坦作为一线治疗时产生持续失眠缓解的疗效;（2）比较一线治疗未能缓解的患者的治疗转换和增强策略的疗效;（3）比较有和无精神病合并症的患者对一线和二线治疗的反应;以及（4）探索所选生物标志物和性状测量作为治疗结果的预测因子的有用性。我们的首要目标是获得有助于制定PI和CMI管理临床指南的新信息。

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.