Repeated Partial Sleep Deprivation to Augment SSRI Response in Depression

描述（由申请人提供）：抑郁症是一种普遍、慢性和复发性精神疾病，具有显著的相关发病率、死亡率和经济成本。尽管抗抑郁药物有效，但治疗反应时间可能长达6-8周，20-35%的患者未能充分反应。为了减轻抑郁症的负担，需要创新的治疗方法，加速抗抑郁作用的开始，增加反应和缓解率。部分睡眠剥夺（PSD）是一种安全的非药物治疗方法，具有抗抑郁疗效，可与抗抑郁药物联合使用以增强治疗效果。我们的试验数据表明，在数周的治疗中，反复服用适量的PSD会改善情绪。我们的数据进一步表明，氟西汀治疗无反应者比无反应者有更短的快速眼动潜伏期和更多的快速眼动睡眠，特别是在晚上的最后几个小时。本研究的目的是评估早期和晚期辅助PSD与无睡眠剥夺（NSD）相比，在增强8周氟西汀20-40 mg治疗效果方面的有效性和安全性，并检查治疗反应的潜在睡眠机制。120名有症状但未服药的抑郁症患者将接受氟西汀20-40毫克，持续8周，并随机分配到床上（TIB）条件下的三种时间之一：(1)无睡眠剥夺（NSD， 2300至0700小时）；(2)早PSD （E-PSD， 0100 ~ 0700时）；或(3)晚PSD （L-PSD， 2300至0500时）。参与者将经历3个实验室前治疗之夜（适应、基线、TIB条件），12个连续使用氟西汀和指定TIB条件的家庭之夜，以及2个治疗后实验室之夜（TIB条件、NSD）。结果测量将包括自我和临床评估的情绪，tib前后的睡眠状况，以及评估PSD程序白天后果的神经行为测试。本研究的具体目的是：(1)比较凌晨2小时部分睡眠剥夺（E-PSD）、深夜2小时部分睡眠剥夺（L-PSD）和无睡眠剥夺（NSD）对抑郁症患者急性情绪的影响；(2)评价氟西汀20-40 mg联合2周重复1小时PSD （E-PSD或L-PSD）治疗抑郁症患者是否比氟西汀20-40 mg加NSD更有效；(3)确定哪些脑电图指标定义治疗反应；(4)评估PSD前、PSD连续1晚和14晚后以及8周临床随访时的神经行为功能。本研究的长期目标是开发一种有效和安全的辅助非药物干预，可以在临床环境中实施，以改善抑郁症患者的临床病程。公共卫生相关性：抑郁症是一种流行的、慢性的、复发性的精神疾病，具有显著的发病率、死亡率和经济成本。抗抑郁药物虽然有效，但可能需要6-8周才能起作用，多达三分之一的患者没有得到适当的治疗反应。需要有效和安全的辅助治疗，以加速抗抑郁药的疗效并提高总体反应率。拟议的研究将测试辅助PSD干预的益处和安全性，这种干预可以很容易地在临床环境中实施，并可能最终大大改善抑郁症患者的临床病程。

DESCRIPTION (provided by applicant): Depression is a prevalent, chronic, and recurrent psychiatric disorder with significant associated morbidity, mortality, and economic costs. Despite the efficacy of antidepressant medications, treatment response time can take as long as 6-8 weeks and 20-35% of patients fail to respond adequately. Innovative treatments that accelerate the onset of antidepressant action and increase response and remission rates are required to reduce depression burden. Partial sleep deprivation (PSD) is a safe non-pharmacological treatment with demonstrated antidepressant efficacy that could be combined with antidepressant medication to augment treatment response. Our pilot data suggest that mood improvement occurs with a modest amount of PSD repeated over weeks of treatment. Our data further suggest that non-responders to fluoxetine treatment have shorter REM latency and more REM sleep than non-responders, particularly in the last few hours of the night. The objectives of the proposed study are to evaluate the efficacy and safety of adjunctive early and late PSD compared to no sleep deprivation (NSD) for augmenting the effects of 8 weeks of fluoxetine 20-40 mg treatment and to examine the underlying sleep mechanisms of treatment response. One hundred and twenty symptomatic but unmedicated depressed patients will receive fluoxetine 20-40 mg for 8 weeks and be randomly assigned to one of three time in bed (TIB) conditions: (1) no sleep deprivation (NSD, 2300 to 0700 hours); (2) early PSD (E-PSD, 0100 to 0700 hours); or (3) late PSD (L-PSD, 2300 to 0500 hours). Participants will undergo three pre-treatment in-laboratory nights (adaptation, baseline, TIB condition), 12 consecutive at- home nights with fluoxetine and the assigned TIB condition, and 2 post-treatment in-laboratory nights (TIB condition, NSD). Outcome measures will include self- and clinician-rated mood, pre-and post-TIB condition sleep, and neurobehavioral testing to evaluate the daytime consequences of the PSD procedure. The specific aims of the study are: (1) to compare the acute mood effects of 2 hours of early-night partial sleep deprivation (E-PSD), 2 hours of late-night partial sleep deprivation (L-PSD), and no sleep deprivation (NSD) in patients with depression; (2) to evaluate whether a treatment combining fluoxetine 20-40 mg with two weeks of repeated 1-hour PSD (E-PSD or L-PSD) is more efficacious than fluoxetine 20-40 mg plus NSD in patients with depression; (3) to determine which EEG measures define treatment response; and (4) to evaluate neurobehavioral functioning before PSD, after 1 and 14 consecutive nights of PSD, and at 8-week clinical follow-up. The long-term objective of this research is to develop an effective and safe adjunctive non- pharmacological intervention that can be implemented in the clinical setting to improve the clinical course for patients with depression. PUBLIC HEALTH RELEVANCE: Depression is a prevalent, chronic, and recurrent psychiatric disorder with significant associated morbidity, mortality, and economic costs. Antidepressant medications, while effective, can take 6-8 weeks to work and up to one-third patients fail to have an adequate treatment response. Efficacious and safe adjunctive treatments that accelerate antidepressant efficacy and improve overall response rates are needed. The proposed study will test the benefit and safety of an adjunctive PSD intervention that can be easily implemented in the clinical setting and that may ultimately substantially improve the clinical course for patients with depression.