Rhodiola rosea Therapy of Major Depressive Disorder

描述(由申请人提供)：这项名为红景天治疗严重抑郁障碍(MDD)的探索性拨款根据PAR-08-135提交给NCCAM，用于在生物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。我们将研究玫瑰花对MDD患者的抗抑郁作用。抑郁症影响着全球超过10亿人，现在被认为是最令人残疾的疾病之一。它占全球疾病总负担的11%以上，并可能导致仅次于癌症和心血管疾病的破坏性后果和功能障碍。它导致严重的社会、职业和个人残疾，并增加了医疗并存和自杀死亡。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。尽管抗抑郁药物疗法的发展简化了MDD的治疗，但由于经济、文化或个人原因，世界上相当一部分人口仍然没有得到治疗。因此，许多人寻求CAM来缓解他们的症状。确定治疗MDD的有效的CAM疗法具有公共卫生意义。玫瑰花属景天科植物，具有悠久的民间药用历史，用于增强身体和情感的耐力。它的适应性或预防性特性也导致它被用于治疗癌症、感染、抑郁症和其他神经系统疾病。几项动物和人体研究表明，玫瑰花可能具有抗抑郁特性。对于特定的第一个目标，我们会问：对于MDD患者，RROSEA是一种安全有效的短期疗法(与舍曲林和安慰剂相比)吗？“为了回答这个问题，符合DSM IV诊断轻度至中度MDD标准的患者将被登记参加为期12周的随机、双盲、安慰剂对照、平行分组的剂量递增研究，即每天服用玫瑰花提取物340-1360毫克与舍曲林50-200毫克。主要的结果衡量标准将是汉密尔顿抑郁17项评分随时间的变化。我们假设罗斯西的疗效优于安慰剂，而疗效与舍曲林相当。对于特定的目标#2，我们会问：与舍曲林和安慰剂相比，玫瑰红花疗法是否能产生良好的耐受性和生活质量(QOL)？为了回答这个问题，我们将获得治疗条件下的安全性和生活质量指标，包括：(I)不良事件的频率、持续时间和严重程度，(Ii)严重不良事件的频率，(Iii)剂量减少的频率，(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，与舍曲林相比，罗西具有更好的耐受性，与安慰剂相比，耐受性相似。我们进一步假设，与舍曲林和安慰剂相比，罗西将拥有更高的生活质量和性表现评级。这项研究的结果将被用来为未来的研究假设提供信息，并估计为未来的大规模研究提供动力所需的效应大小。 公共卫生相关性：此应用程序符合PAR-08-135的公共卫生意图，用于在人体上进行基于生物的补充和替代医学(CAM)疗法的安全性、有效性、毒性和最佳剂量的临床试验。这是对一种新的治疗严重抑郁障碍(MDD)的探索性研究，MDD是一种原因不明的衰弱疾病。这项研究将使用最先进的临床试验技术来评估红景天治疗轻中度MDD患者的安全性、有效性和最佳剂量。这项研究的结果将被用来为未来的研究假设提供依据，并估计进行未来大规模CAM研究所需的效应大小。

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.