Selective serotonin reuptake inhibitors for premenstrual syndrome and premenstrual dysphoric disorder.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 39140320 · doi:10.1002/14651858.CD001396.pub4
What was done
Authors conducted a Cochrane systematic review and meta-analysis of randomized controlled trials up to November 2023 comparing SSRIs (fluoxetine, paroxetine, sertraline, escitalopram, citalopram) with placebo in women prospectively diagnosed with PMS, PMDD, or late luteal phase dysphoric disorder. Continuous and luteal-phase-only regimens were compared. Standardized mean differences (SMDs) and odds ratios (ORs) were calculated using random-effects models, with certainty rated using GRADE.
What was found
The review included 34 RCTs. SSRIs probably reduced overall self-rated premenstrual symptoms compared to placebo (SMD -0.57, 95% CI -0.72 to -0.42; I² = 51%; 12 studies, 1742 participants; moderate certainty). Continuous administration was more effective than luteal phase dosing (P = 0.03 for subgroup difference; continuous: SMD -0.69, 95% CI -0.88 to -0.51; luteal phase: SMD -0.39, 95% CI -0.58 to -0.21). SSRIs significantly increased multiple adverse effects, including tremor (OR 5.38, 95% CI 2.20 to 13.16), nausea (OR 3.30, 95% CI 2.58 to 4.21), asthenia/decreased energy (OR 3.28, 95% CI 2.16 to 4.98), somnolence/decreased concentration (OR 3.26, 95% CI 2.01 to 5.30), dry mouth (OR 2.70), constipation (OR 2.39), sexual dysfunction/decreased libido (OR 2.32, 95% CI 1.57 to 3.42), sweating (OR 2.17), diarrhoea (OR 2.06), insomnia (OR 1.99), dizziness/vertigo (OR 1.96), and fatigue/sedation (OR 1.52).
Why it matters
This review provides updated evidence that SSRIs effectively reduce premenstrual symptoms, with greater benefit seen with continuous daily dosing compared to luteal-phase-only administration, while delineating the risk profile of common adverse events.
Limits
Sixty-eight percent of the included trials were funded by pharmaceutical companies. Included studies suffered from poor reporting of methodology, moderate heterogeneity in overall symptom reduction, and suspected publication bias for response rate analyses. Somnolence and decreased concentration had only low-certainty evidence.