Rhodiola rosea Therapy of Major Depressive Disorder

描述（由申请人提供）：这项探索性资助，题为红景天治疗抑郁症（MDD），根据PAR-08-135提交给NCCAM进行人体安全性和有效性试验的补充和替代医学（CAM）领域的生物为基础的做法。本研究拟对R. MDD患者的玫瑰花。抑郁症影响着全世界10亿多人，现在被认为是最致残的医疗条件之一。它占全球总疾病负担的11%以上，可导致破坏性后果和功能障碍，仅次于癌症和心血管疾病。它会导致严重的社会、职业和个人残疾，并增加医疗并发症和自杀死亡。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MDD的治疗，但世界上仍有相当一部分人口因经济、文化或个人原因而未得到治疗。因此，许多人寻求CAM来缓解他们的症状。确定有效的CAM治疗MDD具有公共卫生相关性。R.蔷薇属景天科植物，作为增强身体和情绪耐力的民间疗法有着悠久的历史。它的适应原或预防特性也导致其用于治疗癌症，感染，抑郁症和其他神经系统疾病。一些动物和人类研究表明，R。迷迭香可能具有抗抑郁的特性。对于具体的目标#1，我们会问：R是。rosea是MDD患者的一种安全有效的短期治疗（与舍曲林和安慰剂相比）？为了回答这个问题，符合DSM IV轻度至中度MDD标准的患者将被纳入一项为期12周的随机、双盲、安慰剂对照、平行组、剂量递增的R.玫瑰提取物340- 1，360 mg/天，舍曲林50-200 mg/天。主要结局指标将是17项汉密尔顿抑郁评分随时间的变化。我们假设R. Rosea将具有优于安慰剂的功效和与舍曲林相当的功效。对于具体的目标#2，我们会问：R。与舍曲林和安慰剂相比，玫瑰花疗法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QOL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）治疗中止的频率，以及（v）QOL和性功能指标。我们假设R. Rosea与舍曲林相比具有上级耐受性，与安慰剂相比具有相似的耐受性。我们进一步假设R. Rosea将具有优于舍曲林和安慰剂的上级QOL和性表现等级。本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量。 公共卫生相关性：本申请符合PAR-08-135的公共卫生目的，即在人体中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。这是一项探索性研究，是一种治疗重度抑郁症（MDD）的新疗法，MDD是一种原因不明的衰弱性疾病。这项研究将使用最先进的临床试验技术来评估红景天在轻度至中度MDD患者中的安全性，有效性和最佳剂量。本研究的结果将用于告知未来的研究假设，并估计进行未来大规模CAM研究所需的效应量。

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.