Symptom-Onset Antidepressant Treatment for PMDD

描述(申请人提供)：经前焦虑症(PMDD)影响3-8%的育龄妇女。这种障碍是一种情绪、行为和身体症状的综合体，在每个月经周期都会扰乱家庭、社会和职业功能。70%患有经前抑郁症的妇女对5-羟色胺再摄取抑制剂(SRIs)的治疗有反应；起效异常迅速，发生在几天内。将SRI的使用限制在月经前2周，似乎提供了与在整个月经周期中连续每日给药类似程度的症状缓解。然而，许多妇女的症状持续1周，对短期(2周)的SRI治疗是否有效还没有进行充分的检查。这种方法将减少PMDD妇女的药物暴露、经济成本和副作用负担；症状出现剂量将更加方便，该方法的参与性可能会提高依从性。虽然一些医生已经开出了症状出现治疗的处方，但它还没有在一项充分有效的安慰剂对照研究中进行测试，如果这种方法无效，会增加患者治疗不足的风险。此外，突然停止SRI可能与停药症状有关，而这一风险尚未得到充分评估。本申请的主要具体目的是：1)评估SRI舍曲林在改善经前症状至月经开始时的PMDD症状方面是否比安慰剂更有效(即“症状开始剂量”)；以及2)评估月经开始时或之后不久停止服药是否与SRI停药症状有关。二次分析将探索症状严重程度、损害身体症状和自杀是否适度治疗反应。300名女性将在三个地点注册：耶鲁医学院、康奈尔大学威尔医学院和弗吉尼亚联邦大学。经过2个月的前瞻性筛查评估后，符合PMDD标准的受试者将被随机接受为期6个月的舍曲林或安慰剂的症状出现治疗。独立的盲人评估者将观察并确认对结果的主观衡量标准的评分。这项研究的结果旨在反映现实生活中的实施情况(即症状出现)，将有助于为患有经前抑郁症的妇女制定实用的治疗指南。

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.