Long-Term Chamomile Therapy of Generalized Anxiety Disorder

描述(由申请人提供)：焦虑症是最常见的精神疾病之一。它们影响了多达25%的美国成年人口。广泛性焦虑症(GAD)是一种慢性、反复发作的疾病。尽管苯二氮类药物和5-羟色胺再摄取抑制剂已成为广泛性焦虑症的主要治疗药物，但这些药物往往与不良副作用、习惯化和戒断症状有关。许多人因经济、文化或个人原因(如精神疾病的耻辱)而拒绝使用传统药物治疗。因此，许多人会寻求替代疗法来治疗他们的焦虑症状。确定治疗广泛性AD的有效替代疗法具有特别重要的意义。在治疗焦虑的替代疗法中，洋甘菊因其镇静作用而被用作传统草药。它的耐受性很好，在焦虑的动物模型中显示出药理活性。尽管它被广泛使用和获得，但关于洋甘菊在广泛性AD中的安全性和有效性的临床试验只有一次。目前的申请寻求建立在先前洋甘菊研究结果的基础上。在这项为期8周的双盲安慰剂对照试验中，我们发现洋甘菊(与安慰剂相比)在减轻GAD症状方面具有显著优势。我们还发现洋甘菊的耐受性非常好(与安慰剂相比)。目前的应用旨在通过进行随机、双盲、平行组、安慰剂替代、洋甘菊在预防GAD复发方面的长期安全性和有效性研究来扩展这些有希望的初步结果。对于特定的目标1，我们会问：“长期的洋甘菊疗法(与安慰剂相比)是否延长了广泛性焦虑症康复后焦虑症状复发的时间？”为了回答这个问题，180名中到重度GAD患者将在8周内每天接受500-1500毫克的开放标签洋甘菊提取物。对洋甘菊有反应的人，在另外4周的巩固治疗中仍然很好，他们将被随机分成双盲持续治疗组，每天服用500-1500毫克洋甘菊或安慰剂，再持续26周。我们假设持续的洋甘菊疗法会导致较长的复发时间(与安慰剂相比)。对于特定的目标#2，我们会问：“对于从广泛性焦虑症中康复的患者，长期的洋甘菊疗法(与安慰剂相比)的相对安全性和耐受性如何？”为了回答这个问题，我们将检查以下结果指标：(I)在每种治疗条件下的患者复发的比例；(Ii)治疗的频率、严重程度和持续时间--紧急不良事件；(Iii)在最初的双盲治疗期间停止症状的频率；以及(Iv)早期研究停止的频率。我们假设洋甘菊疗法将导致较低比例的焦虑症复发和较低的研究中止率(与安慰剂相比)。我们进一步假设，洋甘菊疗法将导致类似频率的停药症状和治疗出现的不良事件(与安慰剂相比)。 公共卫生相关性：这项名为“广泛性焦虑症的长期洋甘菊疗法”的申请正在根据PA-07-070提交给NIH/NCCAM。我们认为，这符合NCCAM的意图，即确定消费者已经在使用的现有替代疗法是否安全有效。目前的申请是基于先前一项题为“洋甘菊疗法治疗广泛性焦虑症”的拨款(R21 AT001916)的初步结果，在该基金中，短期洋甘菊疗法被发现在减少焦虑症状方面优于安慰剂。研究还发现，甘菊的耐受性很好。目前的应用将通过研究洋甘菊在预防焦虑症复发方面的长期益处来扩展这些有希望的结果。

DESCRIPTION (provided by applicant): Anxiety disorders are among the most common psychiatric conditions. They affect up to 25% of the US adult population. Generalized anxiety disorder (GAD) is a chronic, recurrent form of the disorder. Although benzodiazepines and serotonin reuptake inhibitors have become the mainstay therapy of GAD, these drugs are often associated with unwanted side effects, habituation, and withdrawal symptoms. Many individuals decline using conventional drug therapy for financial, cultural, or personal reasons such as the stigma of mental illness. As a result, many individuals will seek alternative therapy for their anxiety symptoms. The identification of effective alternative therapies for GAD would be of particular relevance. Among alternative therapies for anxiety, chamomile has been used as a traditional herbal medicine for its calming effect. It is well tolerated and demonstrates pharmacological activity in animal models of anxiety. Despite its widespread use and availability, there has been only one clinical trial of chamomile safety and efficacy in GAD. The current application seeks to build upon the results of that prior chamomile study. In that 8-week, double-blind, placebo- controlled trial, we found a significant superiority of chamomile (vs. placebo) in reducing GAD symptoms. We also found chamomile to be exceedingly well tolerated (vs. placebo). The current application seeks to extend these promising preliminary results by conducting a randomized, double-blind, parallel group, placebo- substitution, long-term safety and efficacy study of chamomile in preventing GAD relapse. For specific aim #1 we will ask: "Does long-term chamomile therapy (vs. placebo) prolong the time to relapse of anxiety symptoms following recovery from GAD?" To answer this question, 180 patients with moderate to severe GAD will receive open-label chamomile extract 500-1,500 mg daily for 8 weeks. Responders to chamomile, who remain well for 4 additional weeks of consolidation therapy, will be randomized to double-blind continuation therapy with chamomile 500-1,500 mg daily or placebo for an additional 26 weeks. We hypothesize that continuation chamomile therapy will result in a prolonged time to relapse (vs. placebo). For specific aim #2 we will ask: "What is the relative safety and tolerability of long-term chamomile therapy (vs. placebo) in patients who have recovered from GAD?" To answer this question, we will examine the following outcome measures: (i) the proportion of patients in each treatment condition who relapse; (ii) the frequency, severity, and duration of treatment-emergent adverse events; (iii) the frequency of discontinuation symptoms during initial double-blind therapy; and, (iv) the frequency of early study discontinuation. We hypothesize that chamomile therapy will result in a lower proportion of anxiety relapses and a lower study discontinuation rate (vs. placebo). We further hypothesize that chamomile therapy will result in a similar frequency of discontinuation symptoms and treatment-emergent adverse events (vs. placebo). PUBLIC HEALTH RELEVANCE: This application, entitled "Long-Term Chamomile Therapy of Generalized Anxiety Disorder," is being submitted to the NIH/NCCAM under PA-07-070. We believe that it comports with the intent of the NCCAM to determine whether available alternative therapies already in use by consumers are safe and effective. The current application builds upon preliminary findings from a prior grant (R21 AT001916) entitled "Chamomile Therapy for Generalized Anxiety Disorder" in which short-term chamomile therapy was found to be superior to placebo in reducing anxiety symptoms. It also found chamomile to be well tolerated. The present application will extend these promising results by studying the long-term benefit of chamomile in preventing relapse of anxiety.