Rhodiola rosea Therapy of Major Depressive Disorder

描述（由申请人提供）：该探索性拨款名为“红景天治疗重度抑郁症（MDD）”，根据PAR-08-135提交给NCCAM，用于在基于生物学的实践领域进行补充和替代医学（CAM）的人体安全性和有效性试验。我们将研究玫瑰红对重度抑郁症患者的抗抑郁作用。抑郁症影响着全世界超过10亿人，现在被认为是最致残的疾病之一。它占全世界总疾病负担的11%以上，可造成毁灭性后果和功能损害，仅次于癌症和心血管疾病。它导致严重的社会、职业和个人残疾，并增加了医疗合并症和自杀死亡。它被认为是一种以神经递质、神经内分泌、免疫和自主神经紊乱为特征的多系统疾病。尽管抗抑郁药物治疗的发展简化了重度抑郁症的治疗，但由于经济、文化或个人原因，世界上仍有相当一部分人未得到治疗。因此，许多人寻求CAM来缓解他们的症状。确定针对重度抑郁症的有效CAM疗法具有公共卫生相关性。玫瑰属天竺葵科，作为一种提高身体和情感耐力的民间偏方有着悠久的历史。它的适应原或预防特性也使其用于治疗癌症、感染、抑郁症和其他神经系统疾病。一些动物和人类的研究表明，玫瑰红可能具有抗抑郁的特性。对于具体目标#1，我们会问：对于重度抑郁症患者来说，玫瑰红素是一种安全有效的短期治疗方法（与舍曲林和安慰剂相比）吗？”为了回答这个问题，符合DSM IV轻度至中度重度抑郁症标准的患者将被纳入一项为期12周、随机、双盲、安慰剂对照、平行组的剂量递增研究，研究对象分别是每天340- 1360毫克的玫瑰提取物和每天50-200毫克的舍曲林。主要的结果测量指标是17项汉密尔顿抑郁评分随时间的变化。我们假设红景天与安慰剂相比具有更好的疗效，与舍曲林相比具有相当的疗效。对于特定的目标#2，我们会问：与舍曲林和安慰剂相比，玫瑰玫瑰治疗是否具有良好的耐受性和生活质量（QOL） ？为了回答这个问题，我们将获得不同治疗条件下的安全性和生活质量指标，包括：(i)不良事件发生的频率、持续时间和严重程度，（ii）严重不良事件发生的频率，（iii）减少剂量的频率，（iv）停止治疗的频率，以及(v)生活质量和性行为指标。我们假设红景天与舍曲林相比具有更好的耐受性，与安慰剂相比具有相似的耐受性。我们进一步假设，与舍曲林和安慰剂相比，玫瑰玫瑰会有更好的生活质量和性表现评分。这项研究的结果将用于为未来的研究假设提供信息，并估计为未来大规模研究提供动力所需的效应大小。

DESCRIPTION (provided by applicant): This exploratory grant, entitled Rhodiola rosea Therapy of Major Depressive Disorder (MDD), is submitted to the NCCAM under PAR-08-135 to perform human safety and efficacy trials of complementary and alternative medicine (CAM) in the domain of biologically-based practices. We will study the antidepressant action of R. rosea in patients with MDD. Depression affects more than a billion people world wide, and is now recognized as one of the most disabling medical conditions. It accounts for more than 11% of the total disease burden worldwide, and can result in devastating consequences and functional impairment exceeded only by that of cancer and cardiovascular disease. It results in substantial social, occupational, and personal disability and in increased medical co-morbidity and death by suicide. It is considered to be a multi-system disorder characterized by neurotransmitter, neuroendocrine, immunologic, and autonomic disturbances. Although the development of antidepressant drug therapy has simplified the treatment of MDD, a substantial segment of the world's population remains untreated for economic, cultural, or personal reasons. As a result, many individuals seek CAM for relief of their symptoms. The identification of effective CAM therapies for MDD is of public health relevance. R. rosea belongs to the family Crassulaceae, and has a long history as a folk remedy for enhancing physical and emotional endurance. Its adaptogen, or preventive, properties have also led to its use in treating cancer, infection, depression, and other nervous system disorders. Several animal and human studies suggest that R. rosea may have antidepressant properties. For specific aim #1, we will ask: Is R. rosea a safe and effective short-term therapy (vs. sertraline and placebo) for patients with MDD?" To answer this question, patients meeting DSM IV criteria for mild to moderate MDD will be enrolled in a 12-week, randomized, double- blind, placebo-controlled, parallel group, dose-escalation study of R. rosea extract 340-1,360 mg daily vs. sertraline 50-200 mg daily. The primary outcome measure will be change over time in the 17-item Hamilton Depression Rating score. We hypothesize that R. rosea will have superior efficacy vs. placebo and comparable efficacy vs. sertraline. For specific aim #2, we will ask: Does R. rosea therapy result in a favorable tolerability and quality of life (QOL) profile vs. sertraline and placebo? To answer this question, we will obtain safety and QOL measures across treatment conditions that include: (i) frequency, duration, and severity of adverse events, (ii) frequency of serious adverse events, (iii) frequency of dosage reduction, (iv) frequency of treatment discontinuation, and (v) QOL and sexual performance measures. We hypothesize that R. rosea will have a superior tolerability profile vs. sertraline, and similar tolerability vs. placebo. We further hypothesize that R. rosea will have superior QOL and sexual performance ratings vs. sertraline and placebo. Results from this study will be used to inform future research hypotheses and to estimate the effect size necessary to power a future, large scale study. PUBLIC HEALTH RELEVANCE: This application comports with the public health intent of PAR-08-135 to perform clinical trials in humans on the safety, efficacy, toxicity, and optimal dosage of biologically-based complementary and alternative medicine (CAM) therapies. It is an exploratory study of a new therapy for Major Depressive Disorder (MDD), a debilitating illness of uncertain cause. This study will use state-of-the-art clinical trial techniques to evaluate the safety, efficacy, and optimal dosage of Rhodiola rosea in patients with mild to moderate MDD. Results from this study will be used to inform future research hypotheses and to estimate the effect size necessary for conducting a future, large scale CAM study.