Symptom-Onset Antidepressant Treatment for PMDD

描述（由申请人提供）：经前焦虑症（PMDD）影响3-8%的育龄妇女。这种疾病是一种复杂的情绪，行为和身体症状，在每个月经周期期间破坏家庭，社会和职业功能。70%的PMDD女性对5-羟色胺再摄取抑制剂（SRI）治疗有反应;反应的发生异常迅速，在几天内发生。在月经前2周限制SRI的使用似乎提供了类似程度的症状缓解，作为整个月经周期的连续每日剂量。然而，许多妇女的症状持续时间<1周，并且对于较短（< 2周）的SRI治疗是否有效的检查不足。这种方法将减少药物暴露，财务成本，副作用的负担，为妇女与PMDD;发病后给药将更方便，参与性的方法可能会提高依从性。虽然一些医生已经开了治疗复发性疾病的处方，但尚未在一项充分的、安慰剂对照的研究中进行测试，如果这种方式无效，则会增加治疗不足的患者的风险。此外，突然停止SRI可能与停药症状有关，并且这种风险尚未得到充分评估。本申请的主要具体目的是：1）当从经前症状开始到月经开始服用胶囊时（即，“初发给药”）;和2）评估在月经开始时或之后不久停药是否与SRI中止症状相关。次要分析将探索症状严重程度、损害身体症状和自杀倾向是否中度治疗反应。300名女性将在3个地点注册：耶鲁大学医学院，康奈尔大学威尔医学院和弗吉尼亚联邦大学。在2个月的前瞻性筛选评估后，符合PMDD标准的受试者将随机接受舍曲林或安慰剂治疗6个月。独立设盲评价者将观察并确认结局主观指标的评分。这项研究的结果，旨在反映现实生活中的实施（即，症状发作），将有助于制定实用的治疗指南，为妇女与PMDD。

DESCRIPTION (provided by applicant): Premenstrual dysphoric disorder (PMDD) affects 3-8% of reproductive age women. The disorder is a complex of mood, behavioral, and physical symptoms that disrupt family, social, and occupational functioning during each menstrual cycle. 70% of women with PMDD respond to treatment with serotonin reuptake inhibitors (SRIs); the onset of response is unusually rapid, occurring within a few days. Restricting SRI use to 2 weeks prior to menses appears to provide a similar degree of symptom relief as continuous daily dosing throughout the menstrual cycle. However, many women have symptoms for <1 week, and there has been inadequate examination of whether a briefer (< 2 week) period of SRI treatment is effective. Such an approach would reduce medication exposure, financial cost, and side effect burden for women with PMDD; symptom-onset dosing would be more convenient and the participatory nature of the approach may enhance compliance. While some practitioners already prescribe symptom-onset treatment, it has not been tested in an adequately powered, placebo-controlled study increasing the risk of under-treating patients if this modality is not effective. Moreover, abruptly stopping SRIs may be associated with discontinuation symptoms and this risk has not been adequately evaluated. The primary specific aims of this application are to: 1) assess whether the SRI sertraline is more effective than placebo at ameliorating symptoms of PMDD when capsules are taken from the point premenstrual symptoms begin through the onset of menses (i.e., "symptom-onset dosing"); and 2) evaluate whether stopping pills at the onset of menses or shortly thereafter is associated with SRI discontinuation symptoms. Secondary analyses will explore whether symptom severity, impairing physical symptoms and suicidality moderate treatment response. 300 women will be enrolled across 3 sites: Yale School of Medicine, Weill Medical College of Cornell University, and Virginia Commonwealth University. Following 2 months of prospective screening assessment, subjects who meet criteria for PMDD will be randomized to symptom-onset treatment with either sertraline or placebo for 6 months. Independent blinded evaluators will observe and confirm scoring on subjective measures of outcome. The findings of this study, designed to reflect real-life implementation (i.e., symptom onset), will assist in developing practical treatment guidelines for women with PMDD.