Meta-analysis: SSRIs in the Treatment of PMS and PMDD

Peter Kovacs, MD


August 04, 2008

Selective Serotonin Reuptake Inhibitors for Premenstrual Syndrome and Premenstrual Dysphoric Disorder: A Meta-Analysis

Shah NR, Jones JB, Aperi J, Shemtov R, Karne A, Borenstein J
Obstet Gynecol. 2008;111:1175-1182



When administered daily or in the luteal phase only, selective serotonin reuptake inhibitors (SSRIs) are associated with an improvement in premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD).

Many women experience certain recurring symptoms during the menstrual cycle. In the majority of cases, these symptoms occur just prior to menstruation. Premenstrual symptoms may be physical symptoms (eg, breast tenderness), mood-related symptoms (eg, irritability), or a combination of these.

Over 100 symptoms have been described during the luteal phase of the menstrual cycle. When these symptoms interfere with normal daily activity and are accompanied by significant anxiety, a more severe form of the condition, PMDD, may be diagnosed. To establish the diagnosis of PMDD, symptoms have to be documented during the luteal phase of 2 subsequent cycles. With the onset of menstruation, an improvement in symptoms needs to be seen. PMS and PMDD have to be differentiated from other psychiatric conditions (depression, anxiety, panic disorder) that may be accompanied by similar complaints, but which can manifest at any time during the menstrual cycle.

There are well standardized measurement tools to objectively assess the presence and severity of physical and emotional complaints as well as global well-being. These tools could be helpful in everyday clinical practice but are particularly important when the effect of a specific treatment is evaluated.

Numerous therapies have been suggested for the management of premenstrual problems. Lifestyle changes (avoidance of caffeine, regular exercise), dietary changes, vitamin and mineral supplements (calcium, vitamin B), diuretics, bromocriptine, herbal products, oral contraceptive pills, progesterone, antidepressants, and SSRIs have all been suggested as effective remedies. When therapies are under investigation, one has to consider a significant placebo effect. Therefore, blinded, placebo-controlled studies should provide the best opportunity to evaluate whether a therapeutic option is effective.

It is now believed that abnormal central nervous system neurotransmitter levels are responsible for the syndrome. SSRIs were shown in several randomized studies to be effective. Various types of medications, in various doses and according to various dosing regimens, have been evaluated. This meta-analysis assessed whether SSRIs are beneficial for the management of PMS or PMDD.

The analysis conducted by Shah and colleagues is based on the results from 29 randomized trials; 2964 women were included. Overall, a significant improvement in PMS- and PMDD-related symptoms was found. SSRIs appear to be similarly effective when used to manage premenstrual symptoms or PMDD. Since symptoms typically occur during the luteal phase, several reports assessed whether intermittent dosing during the second half of the menstrual cycle only led to a reduction in the severity of symptoms. Intermittent dosing was associated with a significant reduction in symptom severity when compared with placebo but was not as good as continuous dosing. Various SSRIs have been studied (fluoxetine, sertraline, paroxetine), and they seem to have similar effects.

Based on the results of this meta-analysis, several conclusions can be drawn. SSRIs are effective for both PMS and for the more severe syndrome form, PMDD. Continuous dosing appears to be superior to intermittent dosing, but intermittent administration is still more effective than placebo. Various SSRIs appear to have similar effects.



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