A CONTROLLED TRIAL OF PHOTOTHERAPY IN RAPID-CYCLING BIPOLAR DISORDER

快速循环双相情感障碍的光疗对照试验

• 批准号: 5203827
• 负责人: E LEIBENLUFT
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5203827
• 关键词: bipolar depression; circadian rhythms; combination therapy; hormone therapy; human subject; human therapy evaluation; melatonin; mental disorder chemotherapy; photostimulus; phototherapy; psychobiology; psychotropic drugs

Patients with rapid cycling bipolar disorder (RCBD) experience at least four episodes of affective illness (depression, hypomania, and/or mania) in a year. They suffer significant morbidity and are frequently resistant to conventional treatments. Results from Z01 MH 02614-01 CPB show that the mood cycles of patients with RCBD may be associated with shifts in the phase (timing) of their circadian rhythms. If so, then the use of light, dark, or melatonin to shift circadian rhythms (or to increase the amplitude of the nocturnal melatonin rhythm, and thereby make the circadian system more resistant to phase shifts) could have therapeutic effects. In this project, we test the clinical effects of midday bright light (vs. low-dose negative ion generator), melatonin (vs. placebo), and dim (vs. bright) light in patients with RCBD. The studies of midday bright light and of melatonin are both outpatient treatment trials in which the experimental treatment is added as an adjunct to a stable medication regimen. The patient uses the experimental and the control treatment for three months each (in randomized order), with a one-month wash-out period in between. Our work with bright light is the most advanced. Bright light therapy may be a useful therapeutic modality in this population because of its rapid onset and offset of action. Patients can be instructed to use the treatment when they are euthymic or depressed but to forego it when they are hypomanic, thereby allowing them to benefit from light's anti- depressant effects without experiencing increased cycling. In a pilot trial of light therapy in patients with RCBD, we obtained preliminary evidence that morning light therapy exacerbated their cycling, evening light therapy had no effect, and midday light therapy had a mood- stabilizing effect. We hypothesize that midday light therapy was therapeutic because it increased the amplitude of nocturnal melatonin secretion, thereby rendering the rhythm more resistant to the phase shifts that appear to be associated with mood cycling. We are now testing this hypothesis, using low-dose negative ion generator as a control condition. In addition to testing the clinical effects of midday light, we will measure the patient's nocturnal melatonin secretion in each experimental condition to test the hypothesis that midday light therapy increases the amplitude of nocturnal melatonin secretion. The second study in this project consists of a trial of 10 mg of oral melatonin, testing its ability to stabilize mood and to consolidate the fragmented sleep patterns frequently seen in patients with RCBD. Finally, the third experiment tests the acute effects of eight hours of bright vs. dim light (adminstered in randomized order) on hypomania. This study will demonstrate whether light has clinical effects in hypomania, and should provide preliminary evidence as to whether exposure to dim light could have therapeutic effects in hypomanic patients.

快速循环型双相情感障碍（RCBD）患者至少经历 4次情感性疾病发作（抑郁、轻躁狂和/或躁狂） 在一年内。 他们的发病率很高， 对常规治疗有抵抗力。 来自Z 01 MH 02614-01 CPB的结果 表明RCBD患者的情绪周期可能与 在他们的昼夜节律的相位（时间）的变化。 如果是这样， 使用光、暗或褪黑激素来改变昼夜节律（或 增加夜间褪黑激素节律的幅度，从而 使昼夜节律系统更能抵抗相位变化） 治疗效果 在这个项目中，我们测试了 正午强光（与低剂量负离子发生器），褪黑激素（与 安慰剂）和昏暗（对比明亮）光。 对正午强光和褪黑激素的研究都是门诊的 治疗试验，其中实验性治疗作为 作为稳定药物治疗方案的辅助。 患者使用 实验和对照治疗各三个月（在 随机顺序），中间有一个月的洗脱期。 我们的工作与明亮的光是最先进的。 明亮的光疗法 可能是这一人群中有用的治疗方式，因为它 动作的快速启动和抵消。可以指导患者使用 治疗时，他们是euthymic或抑郁，但放弃它时，他们 是轻躁狂，从而使他们受益于光的抗- 在不增加循环的情况下消除影响。 以试点 在RCBD患者的光疗法试验中，我们获得了初步的 有证据表明，早晨的光疗法加剧了他们的自行车，晚上， 光疗法没有效果，中午光疗法有一种情绪， 稳定效果 我们假设正午光线疗法 因为它增加了夜间褪黑激素的幅度 分泌，从而使节律更能抵抗 这些变化似乎与情绪循环有关。 我们现在 为了验证这一假设，使用低剂量负离子发生器作为 控制条件 除了测试正午的临床效果外 我们将测量患者夜间褪黑激素的分泌， 每一个实验条件，以测试假设，正午的光， 治疗增加了夜间褪黑激素分泌的幅度。 该项目的第二项研究包括10 mg口服 褪黑激素，测试其稳定情绪和巩固 在RCBD患者中常见的碎片化睡眠模式。 最后，第三个实验测试了八小时的急性效应。 明亮与昏暗的光（以随机顺序给药）对轻躁狂的影响。 这项研究将证明光是否具有临床效果， 轻度躁狂，并应提供初步证据，以是否暴露 昏暗的光线可能对轻躁狂患者有治疗作用。