ArticlesEfficacy of selective serotonin-reuptake inhibitors in premenstrual syndrome: a systematic review
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.
Section snippets
Trials
We searched databases for reports of published clinical trials of SSRIs in the management of PMS. MeSH terms used were premenstrual syndrome and SSRI, together with title and abstract searches for keywords serotonin and SSRI, premenstrual syndrome, premenstrual dysphoria, premenstrual tension, late luteal-phase dysphoric disorder, and premenstrual dysphoric disorder. We contacted pharmaceutical companies that manufacture SSRIs. The trials were identified by searches of EMBASE (1988 to 1998),
Results
We identified 29 published trials of SSRIs in the management of PMS. Of these, ten trials12, 13, 14, 15, 16, 17, 18, 19, 20, 21 were open and did not include a placebo group,20 three were preliminary reports of included trials22, 23, 24 and one was of low quality25 as determined by the Jadad score. Thus, 15 randomised placebo-controlled trials were included in the meta-analysis (table 1).6, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 One trial6 used two dosing regimens and another26
Discussion
The pooled standardised mean difference for the effect of SSRIs on PMS strongly favours treatment over placebo.
We found no significant evidence of bias in study selection, and our check of unreported negative trials confirmed that there would need to be twice as many missing trials as existing published trials. The existence of so many unreported trials is unlikely, and therefore the pooled standardised mean difference is unlikely to be a result of biased study sampling. A subanalysis of the
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