SYSTEMATIC REVIEW
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Selective serotonin reuptake inhibitors for premenstrual syndrome.

BACKGROUND: This is a substantive update of a previous review. Severe premenstrual syndrome (PMS) affects between 3% to 5% of women of reproductive age. Severe PMS is classified under the Diagnostic and Statistical Manual of Mental Disorders as premenstrual dysphoric disorder (PMDD). Selective serotonin reuptake inhibitors (SSRIs) are increasingly used as front-line therapy for PMS. A systematic review was undertaken on the efficacy of SSRIs in the management of severe PMS, or PMDD, to assess the evidence for this treatment option.

OBJECTIVES: The objective of this review was to evaluate the effectiveness of SSRIs in reducing premenstrual syndrome symptoms in women diagnosed with severe premenstrual syndrome.

SEARCH STRATEGY: Electronic searches for relevant randomised controlled trials were undertaken in the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, PsycInfo, and CINAHL (March 2008). Where insufficient data were presented in a report the original authors were contacted for further details.

SELECTION CRITERIA: All trials were considered in which women with a prospective diagnosis of PMS, PMDD or late luteal phase dysphoric disorder (LPDD) were randomised to receive SSRIs or placebo for the treatment of premenstrual syndrome in a blinded trial.

DATA COLLECTION AND ANALYSIS: Forty randomised controlled trials were identified which reported the use of SSRIs in the management of PMS. Fifty-six trials were excluded. The review authors extracted the data independently and estimated standardised mean differences for continuous outcomes.

MAIN RESULTS: Due to heterogeneity, analyses were subgrouped into change and absolute scores. The primary analysis of reduction in overall symptomatology included data on 2294 women with premenstrual syndrome. SSRIs were found to be highly effective in treating the premenstrual symptoms (SMD -0.53, 95% CI 0.68 to -0.39; P < 0.00001). Secondary analysis showed that they were effective in treating physical (SMD -0.34, 95% CI -0.45 to -0.22; P < 0.00001), functional (SMD -0.30, 95% CI -0.43 to -0.17; P < 0.00001), and behavioural symptoms (SMD -0.41, 95% CI -0.53 to -0.29; P < 0.00001). Luteal phase only and continuous administration were both effective and there was no influence of a placebo run-in period on reduction in symptoms. All SSRIs (fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and clomipramine) were effective in reducing premenstrual symptoms. Withdrawals due to side effects were twice as likely to occur in the treatment group (OR 2.18, 95% CI 1.62 to 2.92; P < 0.00001).

AUTHORS' CONCLUSIONS: The evidence supports the use of selective serotonin reuptake inhibitors in the management of severe premenstrual syndrome.

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