Efficacy of selective serotonin-reuptake inhibitors in premenstrual syndrome: a systematic review

Summary

Background

Selective serotonin-reuptake inhibitors (SSRIs) are increasingly being used as first-line therapy for severe premenstrual syndrome (PMS). We undertook a meta-analysis on the efficacy of SSRIs in this disorder.

Methods

We searched medical and scientific databases, approached pharmaceutical companies, and reviewed citations of relevant articles to identify 29 studies of the use of SSRIs in PMS. 14 were excluded (no placebo group, preliminary report of included trial, or low quality). 15 randomised placebo-controlled trials were included. Information on study design, participants, drugs used and dosing regimens, outcome measures, sideeffects, and sources of funding was extracted. Standardised mean differences between treatment and placebo groups were calculated to obtain an overall estimate of efficacy. The primary outcome measure was a reduction in overall PMS symptoms.

Findings

The primary analysis included data on 904 women (570 assigned active treatment and 435 assigned placebo, including 101 in crossover trials). The overall standardised mean difference was −1·066 (95% CI −1·381 to −0·750), which corresponds to an odds ratio of 6·91 (3·90 to 12·2) in favour of SSRIs. SSRIs were effective in treating physical and behavioural symptoms. There was no significant difference in symptom reduction between continuous and intermittent dosing or between trials funded by pharmaceutical companies and those independently funded. Withdrawal due to sideeffects was 2·5 times more likely in the active-treatment group than in the placebo group.

Interpretation

SSRIs are an effective first-line therapy for severe PMS. The safety of these drugs has been demonstrated in trials of affective disorder, and the side-effects at low doses are generally acceptable.

Introduction

Premenstrual syndrome (PMS) consists of regularly recurring psychological or somatic symptoms, or both; the symptoms occur specifically during the luteal phase of the cycle and are relieved by the onset of, or during, menstruation.¹ Mild physiological symptoms occur in about 95% of all women of reproductive age and can be managed by conservative lifestyle changes such as alterations in diet. However, for about 5% of women, symptoms are so severe that their lives are completely disrupted during the second half of the cycle; many of these women require pharmacological management.² Such severe PMS is classified under the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, as premenstrual dysphoric disorder.

The causes of PMS remain unclear and speculative, although many hypotheses have been advanced and many treatments suggested. Moreover, because there is a substantial placebo response, uncontrolled trials have resulted in a proliferation of claims for ineffective therapies. The current consensus is that differential sensitivity to circulating hormones, rather than abnormal hormone concentrations, causes PMS.³ There is increasing evidence that serotonin is important in the pathogenesis of PMS,4, 5 and selective serotonin-reuptake inhibitors (SSRIs) are increasingly being used as the first-line therapy.⁶ Fluoxetine has recently been licensed in the UK for premenstrual dysphoric disorder, and has received full approval from the US Food and Drug Administration this year.

We undertook this review to assess the efficacy of SSRIs in the management of severe PMS.