St. John's Wort vs Placebo in Social Phobia

描述（由申请人提供）：社交恐惧症是一种普遍的， 使人衰弱的疾病，终生患病率为13.3%。 社交恐惧症患者被发现在功能上受损， 教育、就业和社会关系领域的质量较差， 自杀意念和精神共病的增加。 双盲研究发现，苯二氮卓类药物，选择性和非选择性 MAOI抑制剂，几种SSRI，以及抗惊厥药普瑞巴林和 加巴喷丁才有效然而，这些化合物的副作用表明， 需要更好耐受的化合物，例如，在帕罗西汀多中心 试验（唯一一种FDA批准适应症的药物），27%的人报告 嗜睡，26%的恶心，37%的男性报告延迟 射精; 34%的患者提前终止试验。一直 圣约翰草（SJW）（金丝桃属 perforatum）作为轻度至中度抑郁症的治疗。已有23 随机试验表明SJW比安慰剂更有效， 治疗轻度至中度抑郁症的门诊患者。SJW很好 耐受，仅在2.5%的病例中观察到轻度副作用， 大型（3250例患者）药物监测研究。药代动力学研究发现 金丝桃对5-羟色胺、多巴胺和GABA α和GABA β有亲和力 受体，其中每一个都与社交恐惧症有关，因此有一个 提示SJW可能对这种疾病有效。这将是一个为期12周， 双盲、安慰剂对照试验，旨在生成效应量数据 这将用于确定性研究所需的样本量。 40例患者将随机分配至SJW（LI 160）或匹配安慰剂组。 这将是一种灵活的剂量设计，从300 mg tid开始，最多 每天1800毫克。将采用意向治疗分析。科目 每周评估一次，持续两周，之后每两周评估一次。主 结果测量将是Liebowitz基线至终点的变化 社交焦虑量表

DESCRIPTION (provided by applicant): Social Phobia is a prevalent and debilitating condition, with a lifetime prevalence rate to be 13.3 percent. Socially phobic patients have been found to be functionally impaired in the areas of education, employment and social relationships, to have poorer quality of life, and increased suicidal ideation and psychiatric comorbidity. Double-blind studies have found benzodiazepines, selective and non-selective MAOI inhibitors, several SSRIs, and the anticonvulsants pregabalin and gabapentin to be effective. However, side effects with these compounds suggests the need for better tolerated compounds, e.g., in the paroxetine multi-center trial (the only drug with an FDA approved indication), 27 percent reported somnolence, 26 percent nausea, and 37 percent of males reported delayed ejaculation; 34 percent of patients discontinued the trial early. There has been considerable worldwide interest in St. John's Wort (SJW) (Hypericum perforatum) as a treatment of mild to moderate depression. There have been 23 randomized trials suggesting SJW is more effective than placebo for the treatment of outpatients with mild to moderate depression. SJW is very well tolerated with mild side effects observed in only 2.5 percent of cases in a large (3250 patients) drug monitoring study. Pharmacokinetic studies have found Hypericum to have affinity for serotonin, dopamine and GABA alpha and GABA beta receptors, each of which have been implicated in social phobia, thus there is a suggestion that SJW may be effective for this disorder. This will be a 12-week, double blind, placebo-controlled trial, designed to generate effect size data that will be used to determine sample size needed to power a definitive study. Forty patients will be randomized to either SJW (LI 160) or matching placebo. This will be a flexible-dose design, starting at 300 mg tid to a maximum of 1800 mg total per day. An intent-to-treat analysis will be employed. Subjects will be evaluated weekly for two weeks, then bi-weekly thereafter. The primary outcome measure will be the change from baseline to endpoint on the Liebowitz Social Anxiety Scale.