Alternative Treatments for Premenstrual Dysphoric Disorder

需要创新的替代疗法来治疗经前焦虑症(PMDD)，这是一种列在DSM-IV中的致残性抑郁障碍，影响到5%-8%的经期妇女。如果不进行治疗，PMDD可能会发展为严重的抑郁症。在提供药物治疗的情况下，至少40%的妇女没有反应、出现有问题的副作用或寻求这种周期性疾病的慢性药物治疗以外的其他选择。此前，我们独立实施睡眠和光行为疗法，将基础昼夜生物学的发现转化为改善经前抑郁症女性健康的发现。为了响应开发新的联合疗法的呼吁，在这项提议中，我们计划联合实施觉醒疗法和光线疗法，这是一种以前从未在PMDD中尝试过的新的替代方法，尽管它在其他情绪障碍方面已被证明有效。这些潜在的互补疗法的优势是，唤醒疗法加速了光线治疗的抗抑郁效果的开始，这在黄体期相对较短的两周症状期间是一个关键的好处，而光线疗法保持了唤醒疗法的短暂效果，否则往往在随后的睡眠后失去。我们的主要目的是检验这些干预措施对情绪的影响，其次是对昼夜节律的影响，以检验关键时间疗法通过纠正褪黑激素和睡眠中的相位干扰来改善情绪的假设。由于我们发现在PMDD患者中，与无症状的卵泡和月经周期阶段相比，有症状的黄体中褪黑激素的节律被延迟(移动-延迟)，我们假设晚醒疗法(LWT：睡眠21：00-01：00小时，然后醒来)加早晨明亮的白光(BWL)比起延迟他们的早醒疗法(EWT：清醒，然后睡眠03：00-07：00小时)更能改善PMDD患者的情绪。观察指标为情绪、尿褪黑素、睡眠/活动。这些研究将确定针对特定潜在昼夜节律异常的创新、替代、组合的时间生物学干预是否可以改善经前抑郁症患者的情绪。这一结果可能会影响其他伴有时间生物学障碍的抑郁障碍和其他女性�S情绪障碍。

Innovative, alternative treatments are needed for Premenstrual Dysphoric Disorder (PMDD), a disabling depressive disorder listed in DSM-IV, affecting 5-8% of menstruating women. Left untreated, PMDD can progress to major depression. Offered medication, at least 40% of women do not respond, develop problematic side-effects or seek options other than chronic pharmacological treatment for this periodic illness. Previously we independently administered sleep and light behavioral therapies, translating discoveries from basic circadian biology to improve the health of women with PMDD. In response to a call for the development of novel combination therapies, in this proposal we plan to co-administer wake therapy followed by light treatment, a novel alternative approach, never before tried in PMDD, despite its demonstrated efficacy in other mood disorders. These potentially complementary treatments have the advantage of wake therapy hastening the onset of the antidepressant effects of light treatment, a crucial benefit during the relatively short-lived symptoms of the 2-week luteal phase, whereas light treatment maintains the benefit of the otherwise transitory effects of wake therapy often lost after subsequent sleep. Our primary aim is to examine the effects of these interventions on mood, and secondarily on circadian rhythms, to test the hypothesis that critically-timed chronotherapy improves mood by correcting phase disturbances in melatonin and sleep. As we found that in PMDD melatonin rhythms were phase-delayed (shifted-later) in the symptomatic luteal compared with the asymptomatic follicular, menstrual cycle phase, we hypothesize that advancing melatonin rhythms with late wake therapy (LWT: sleep 21:00-01:00 h, followed by wake) plus morning bright white light (BWL) will improve mood in PMDD patients more than delaying them with early wake therapy (EWT: wake, then sleep 03:00-07:00 h) plus evening BWL. Outcome measures are mood, urinary melatonin, sleep/activity in PMDD subjects. These studies will determine whether innovative, alternative, combined chronobiological interventions, targeted to specific underlying circadian rhythm abnormalities, can benefit mood in PMDD. The results may impact other depressive disorders with chronobiological disturbances and other women�s mood disorders.