Centre for Evidence-Based Medicine Odense (CEBMO) and Cochrane Denmark, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Open Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark.
Cochrane Database Syst Rev. 2024 Aug 14;8(8):CD001396. doi: 10.1002/14651858.CD001396.pub4.
BACKGROUND: Premenstrual syndrome (PMS) is a combination of physical, psychological and social symptoms in women of reproductive age, and premenstrual dysphoric disorder (PMDD) is a severe type of the syndrome, previously known as late luteal phase dysphoric disorder (LLPDD). Both syndromes cause symptoms during the two weeks leading up to menstruation (the luteal phase). Selective serotonin reuptake inhibitors (SSRIs) are increasingly used as a treatment for PMS and PMDD, either administered in the luteal phase or continuously. We undertook a systematic review to assess the evidence of the positive effects and the harms of SSRIs in the management of PMS and PMDD. OBJECTIVES: To evaluate the benefits and harms of SSRIs in treating women diagnosed with PMS and PMDD. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase and PsycINFO for randomised controlled trials (RCTs) in November 2023. We checked reference lists of relevant studies, searched trial registers and contacted experts in the field for any additional trials. This is an update of a review last published in 2013. SELECTION CRITERIA: We considered studies in which women with a prospective diagnosis of PMS, PMDD or LLPDD were randomised to receive SSRIs or placebo. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We pooled data using a random-effects model. We calculated standardised mean differences (SMDs) with 95% confidence intervals (CIs) for premenstrual symptom scores, using 'post-treatment' scores for continuous data. We calculated odds ratios (ORs) with 95% CIs for dichotomous outcomes. We stratified analyses by type of administration (luteal phase or continuous). We calculated absolute risks and the number of women who would need to be taking SSRIs in order to cause one additional adverse event (i.e. the number needed to treat for an additional harmful outcome (NNTH)). We rated the overall certainty of the evidence for the main findings using GRADE. MAIN RESULTS: We included 34 RCTs in the review. The studies compared SSRIs (i.e. fluoxetine, paroxetine, sertraline, escitalopram and citalopram) to placebo. SSRIs probably reduce overall self-rated premenstrual symptoms in women with PMS and PMDD (SMD -0.57, 95% CI -0.72 to -0.42; I = 51%; 12 studies, 1742 participants; moderate-certainty evidence). SSRI treatment was probably more effective when administered continuously than when administered only in the luteal phase (P = 0.03 for subgroup difference; luteal phase group: SMD -0.39, 95% CI -0.58 to -0.21; 6 studies, 687 participants; moderate-certainty evidence; continuous group: SMD -0.69, 95% CI -0.88 to -0.51; 7 studies, 1055 participants; moderate-certainty evidence). The adverse effects associated with SSRIs were nausea (OR 3.30, 95% CI 2.58 to 4.21; I = 0%; 18 studies, 3664 women), insomnia (OR 1.99, 95% CI 1.51 to 2.63; I = 0%; 18 studies, 3722 women), sexual dysfunction or decreased libido (OR 2.32, 95% CI 1.57 to 3.42; I = 0%; 14 studies, 2781 women), fatigue or sedation (OR 1.52, 95% CI 1.05 to 2.20; I = 0%; 10 studies, 1230 women), dizziness or vertigo (OR 1.96, 95% CI 1.36 to 2.83; I = 0%; 13 studies, 2633 women), tremor (OR 5.38, 95% CI 2.20 to 13.16; I = 0%; 4 studies, 1352 women), somnolence and decreased concentration (OR 3.26, 95% CI 2.01 to 5.30; I = 0%; 8 studies, 2050 women), sweating (OR 2.17, 95% CI 1.36 to 3.47; I = 0%; 10 studies, 2304 women), dry mouth (OR 2.70, 95% CI 1.75 to 4.17; I = 0%; 11 studies, 1753 women), asthenia or decreased energy (OR 3.28, 95% CI 2.16 to 4.98; I = 0%; 7 studies, 1704 women), diarrhoea (OR 2.06, 95% CI 1.37 to 3.08; I = 0%; 12 studies, 2681 women), and constipation (OR 2.39, 95% CI 1.09 to 5.26; I = 0%; 7 studies, 1022 women). There was moderate-certainty evidence for all adverse effects other than somnolence/decreased concentration, which was low-certainty evidence. Overall, the certainty of the evidence was moderate. The main weakness was poor reporting of study methodology. Heterogeneity was low or absent for most outcomes, although there was moderate heterogeneity in the analysis of overall self-rated premenstrual symptoms. Based on the meta-analysis of response rate (the outcome with the most included studies), there was suspected publication bias. In total, 68% of the included studies were funded by pharmaceutical companies. This stresses the importance of interpreting the review findings with caution. AUTHORS' CONCLUSIONS: SSRIs probably reduce premenstrual symptoms in women with PMS and PMDD and are probably more effective when taken continuously compared to luteal phase administration. SSRI treatment probably increases the risk of adverse events, with the most common being nausea, asthenia and somnolence.
背景:经前期综合征(PMS)是育龄妇女的一组身心和社会症状,经前期烦躁障碍(PMDD)是其严重形式,以前称为黄体晚期烦躁障碍(LLPDD)。这两种综合征都会在月经前两周(黄体期)出现症状。选择性 5-羟色胺再摄取抑制剂(SSRIs)越来越多地被用作治疗 PMS 和 PMDD 的方法,可在黄体期或连续治疗时使用。我们进行了一项系统评价,以评估 SSRIs 在管理 PMS 和 PMDD 中的积极作用和危害。 目的:评估 SSRIs 治疗患有 PMS 和 PMDD 的女性的益处和危害。 检索方法:我们于 2023 年 11 月检索了 Cochrane 妇科和生殖(CGF)专门注册试验、CENTRAL、MEDLINE、Embase 和 PsycINFO 中的随机对照试验(RCT)。我们检查了相关研究的参考文献列表、试验登记册,并联系了该领域的专家以获取任何其他试验。这是对 2013 年发表的一篇综述的更新。 选择标准:我们考虑了前瞻性诊断为 PMS、PMDD 或 LLPDD 的女性被随机分配接受 SSRIs 或安慰剂的研究。 数据收集和分析:我们使用标准的 Cochrane 方法。我们使用随机效应模型合并数据。我们使用“治疗后”评分计算经前期症状评分的标准化均数差(SMD),使用连续数据。我们使用二分类结局的比值比(OR)计算。我们按管理方式(黄体期或连续)进行分层分析。我们计算了需要服用 SSRIs 的妇女数量(即治疗副作用的人数),以引起一个额外的不良事件(即治疗不良结果的需要治疗人数(NNTH))。我们使用 GRADE 评估主要发现的证据总体确定性。 主要结果:我们纳入了 34 项 RCT。这些研究比较了 SSRIs(即氟西汀、帕罗西汀、舍曲林、依西酞普兰和西酞普兰)与安慰剂。SSRIs 可能减轻患有 PMS 和 PMDD 的女性的整体自评经前期症状(SMD-0.57,95%CI-0.72 至-0.42;I=51%;12 项研究,1742 名参与者;中等确定性证据)。与仅在黄体期给药相比,持续给药可能更有效(亚组差异 P=0.03;黄体期组:SMD-0.39,95%CI-0.58 至-0.21;6 项研究,687 名参与者;中等确定性证据;连续组:SMD-0.69,95%CI-0.88 至-0.51;7 项研究,1055 名参与者;中等确定性证据)。SSRIs 相关的不良反应包括恶心(OR 3.30,95%CI 2.58 至 4.21;I=0%;18 项研究,3664 名女性)、失眠(OR 1.99,95%CI 1.51 至 2.63;I=0%;18 项研究,3722 名女性)、性功能障碍或性欲减退(OR 2.32,95%CI 1.57 至 3.42;I=0%;14 项研究,2781 名女性)、疲劳或镇静(OR 1.52,95%CI 1.05 至 2.20;I=0%;10 项研究,1230 名女性)、头晕或眩晕(OR 1.96,95%CI 1.36 至 2.83;I=0%;13 项研究,2633 名女性)、震颤(OR 5.38,95%CI 2.20 至 13.16;I=0%;4 项研究,1352 名女性)、嗜睡和注意力不集中(OR 3.26,95%CI 2.01 至 5.30;I=0%;8 项研究,2050 名女性)、出汗(OR 2.17,95%CI 1.36 至 3.47;I=0%;10 项研究,2304 名女性)、口干(OR 2.70,95%CI 1.75 至 4.17;I=0%;11 项研究,1753 名女性)、乏力或精力不足(OR 3.28,95%CI 2.16 至 4.98;I=0%;7 项研究,1704 名女性)、腹泻(OR 2.06,95%CI 1.37 至 3.08;I=0%;12 项研究,2681 名女性)和便秘(OR 2.39,95%CI 1.09 至 5.26;I=0%;7 项研究,1022 名女性)。除了嗜睡/注意力不集中,其他不良反应的证据确定性为中度,而后者的证据确定性为低度。总体而言,证据的确定性为中度。主要弱点是研究方法报告不佳。大多数结局的异质性较低或不存在,但整体自评经前期症状的分析存在中度异质性。基于对反应率(包含研究最多的结局)的荟萃分析,疑似存在发表偏倚。总共,68%的纳入研究由制药公司资助。这强调了谨慎解释审查结果的重要性。 作者结论:SSRIs 可能减轻患有 PMS 和 PMDD 的女性的经前期症状,且连续治疗可能比黄体期给药更有效。SSRIs 治疗可能会增加不良反应的风险,最常见的是恶心、乏力和嗜睡。
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