Marjoribanks · The Cochrane database of systematic reviews 2013 · systematic review and meta-analysis of randomized controlled trials · n=31 studies

Selective serotonin reuptake inhibitors for premenstrual syndrome.

Cited 413 times in the scientific literature.

Level 1 - systematic review of randomized trials

Systematic review and meta-analysis of randomized controlled trials

PubMed 23744611 · doi:10.1002/14651858.CD001396.pub3 · record verified 2026-08-26

What was done

A Cochrane systematic review and meta-analysis evaluated the effectiveness and safety of selective serotonin reuptake inhibitors (SSRIs: fluoxetine, paroxetine, sertraline, escitalopram, and citalopram) versus placebo for premenstrual syndrome (PMS), PMDD, or late luteal phase dysphoric disorder. Searches across multiple databases up to February 2013 identified 31 randomized controlled trials (RCTs). Primary outcomes were premenstrual symptom scores pooled with random-effects models calculating standardized mean differences (SMDs) and adverse event withdrawals calculated as odds ratios (ORs), stratified by dosing timing (luteal-phase vs continuous) and dose level. Evidence certainty was assessed using GRADE.

What was found

SSRIs significantly reduced overall self-rated premenstrual symptoms compared with placebo: - Moderate-dose SSRIs reporting end scores: SMD -0.65 (95% CI -0.84 to -0.46; 9 studies, 1,276 women; I² = 58%; low-quality evidence). - Moderate-dose SSRIs reporting change scores: SMD -0.36 (95% CI -0.51 to -0.20; 4 studies, 657 women; I² = 29%; moderate-quality evidence). - Both luteal-phase-only and continuous regimens were effective, with no clear difference between administration strategies. - Withdrawals due to adverse effects were higher with moderate-dose SSRIs than placebo (OR 2.55, 95% CI 1.84 to 3.53; 15 studies, 2,447 women; I² = 0%; moderate-quality evidence). - Common side effects at moderate doses included nausea (NNH = 7), asthenia/decreased energy (NNH = 9), somnolence (NNH = 13), fatigue (NNH = 14), decreased libido (NNH = 14), and sweating (NNH = 14). Adverse effects were dose-related.

Why it matters

This review establishes that SSRIs provide effective relief for premenstrual syndrome symptoms and demonstrates that luteal-phase-only dosing is as effective as continuous administration, allowing for targeted intermittent therapy.

Limits

The overall evidence quality was rated low to moderate, predominantly due to poor methodological reporting in the included primary trials. Few studies directly compared luteal-phase and continuous regimens head-to-head. Total participant enrollment across all 31 included RCTs was not reported in the abstract.

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