Selective serotonin reuptake inhibitors (SSRIs) for premenstrual syndrome

Premenstrual syndrome (PMS) is a common cause of physical, psychological and social problems in women of reproductive age. PMS is distinguished from 'normal' premenstrual symptoms by the degree of distress and disruption it causes. Symptoms occur during the period leading up to the menstrual period and are relieved by the onset of menstruation. Common symptoms include irritability, depression, anxiety and lethargy. A clinical diagnosis of PMS requires that the symptoms are confirmed by prospective recording (that is recorded as they occur) for at least two menstrual cycles and that they cause substantial distress or impairment to daily life. It is estimated that approximately one in five women of reproductive age are affected. PMS can severely disrupt a woman's daily life and some women seek medical treatment. Researchers in The Cochrane Collaboration reviewed the evidence about the effectiveness and safety of selective serotonin reuptake inhibitors (SSRIs) for treating PMS. They examined the research up to February 2013.

The review included 31 randomised controlled trials which compared SSRIs with placebo in a total of 4372 women who were clinically diagnosed with PMS. SSRIs were found to be effective for reducing the overall symptoms of PMS and also for reducing specific types of symptoms (psychological, physical and functional symptoms, and irritability). SSRIs were usually taken for about two weeks before the start of the menstrual period (the luteal phase) or every day (continuously). Both regimens appeared to be equally effective, although more research is needed to confirm this.

Adverse effects were more common in the women taking SSRIs than in those taking placebo. The most commonly occurring side effects were nausea and decreased energy. The review authors calculated that nausea is likely to occur as a drug side effect in approximately one out of seven women with PMS taking a moderate dose of SSRIs, and lack of energy is likely to occur as a drug side effect in approximately one out of every nine women.

The overall quality of the evidence was rated as low to moderate, the main weakness being poor reporting of methods in the included studies. At least 21 of the studies received funding from pharmaceutical companies.

Authors' conclusions: 

SSRIs are effective in reducing the symptoms of PMS, whether taken in the luteal phase only or continuously. Adverse effects are relatively frequent, the most common being nausea and asthenia. Adverse effects are dose-dependent.

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Background: 

Premenstrual syndrome (PMS) is a common cause of physical, psychological and social problems in women of reproductive age. The key characteristic of PMS is the timing of symptoms, which occur only during the two weeks leading up to menstruation (the luteal phase of the menstrual cycle). Selective serotonin reuptake inhibitors (SSRIs) are increasingly used as first line therapy for PMS. SSRIs can be taken either in the luteal phase or else continuously (every day). SSRIs are generally considered to be effective for reducing premenstrual symptoms but they can cause adverse effects.

Objectives: 

The objective of this review was to evaluate the effectiveness and safety of SSRIs for treating premenstrual syndrome.

Search strategy: 

Electronic searches for relevant randomised controlled trials (RCTs) 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 (February 2013). Where insufficient data were presented in a report, attempts were made to contact the original authors for further details.

Selection criteria: 

Studies 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.

Data collection and analysis: 

Two review authors independently selected the studies, assessed eligible studies for risk of bias, and extracted data on premenstrual symptoms and adverse effects. Studies were pooled using random-effects models. Standardised mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for premenstrual symptom scores, using separate analyses for different types of continuous data (that is end scores and change scores). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes. Analyses were stratified by type of drug administration (luteal or continuous) and by drug dose (low, medium, or high). We calculated the number of women who would need to be taking a moderate dose of SSRI in order to cause one additional adverse event (number needed to harm: NNH). The overall quality of the evidence for the main findings was assessed using the GRADE working group methods.

Main results: 

Thirty-one RCTs were included in the review. They compared fluoxetine, paroxetine, sertraline, escitalopram and citalopram versus placebo. SSRIs reduced overall self-rated symptoms significantly more effectively than placebo. The effect size was moderate when studies reporting end scores were pooled (for moderate dose SSRIs: SMD -0.65, 95% CI -0.46 to -0.84, nine studies, 1276 women; moderate heterogeneity (I2 = 58%), low quality evidence). The effect size was small when studies reporting change scores were pooled (for moderate dose SSRIs: SMD -0.36, 95% CI -0.20 to -0.51, four studies, 657 women; low heterogeneity (I2=29%), moderate quality evidence).

SSRIs were effective for symptom relief whether taken only in the luteal phase or continuously, with no clear evidence of a difference in effectiveness between these modes of administration. However, few studies directly compared luteal and continuous regimens and more evidence is needed on this question.

Withdrawals due to adverse effects were significantly more likely to occur in the SSRI group (moderate dose: OR 2.55, 95% CI 1.84 to 3.53, 15 studies, 2447 women; no heterogeneity (I2 = 0%), moderate quality evidence). The most common side effects associated with a moderate dose of SSRIs were nausea (NNH = 7), asthenia or decreased energy (NNH = 9), somnolence (NNH = 13), fatigue (NNH = 14), decreased libido (NNH = 14) and sweating (NNH = 14). In secondary analyses, SSRIs were effective for treating specific types of symptoms (that is psychological, physical and functional symptoms, and irritability). Adverse effects were dose-related.

The overall quality of the evidence was low to moderate, the main weakness in the included studies being poor reporting of methods. Heterogeneity was low or absent for most outcomes, though (as noted above) there was moderate heterogeneity for one of the primary analyses.

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