Premenstrual Syndromes: What is the Optimal Duration of Treatment?

Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD) affect a large number of women of childbearing age. 30-80% of reproductive age women experience premenstrual symptoms. PMS refers to a pattern of physical, emotional, and behavioral symptoms occurring 1-2 weeks before menses and remitting with the onset of menses. Common symptoms include fatigue, poor concentration, mild mood changes, headaches, abdominal bloating, and breast tenderness.

PMDD is a less common, but more severe syndrome, affecting 3-8% of women in their reproductive years. Common symptoms of PMDD are irritability, depressed mood, anxiety, and/or mood swings, which occur 1-2 weeks prior to menstruation, and result in marked social, occupational, or interpersonal impairment.

Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological treatments for PMS and PMDD. Women generally respond rapidly and effectively to low doses of SSRIs. A significant number of research studies support the effectiveness of SSRIs in treating the physical and emotional symptoms of PMS and PMDD. SSRIs may be prescribed continuously throughout the menstrual cycle, or may be given in intermittent fashion during the luteal phase of the cycle (days 14-28).

Once the symptoms have remitted with an SSRI, how long should a woman continue to take the medication?

This question has been understudied. Earlier research in which luteal phase fluoxetine (Prozac) or placebo was used to treat PMDD for 3 months in a variety of dosing regimens showed a recurrence of PMDD symptoms within the first cycle after treatment discontinuation (Pearlstein et al, 2003).

A recent study suggests that the optimal duration of treatment for premenstrual syndromes may depend on symptom severity. This randomized, double-blind study included 174 women with PMS or PMDD who were treated with the SSRI sertraline (Zoloft) 50 mg daily during the luteal phase of the menstrual cycle. A switch to 100 mg daily could be made in the absence of response in the second or third month of treatment. Half of the participants took sertraline for 4 months followed by placebo for 8 months; the other half took sertraline for the entire 12 months. All participants then took a placebo for 6 months. Symptom assessments were performed monthly.

Rates of relapse, defined as symptoms returning to the pre-treatment level, were compared for each group. The results showed higher rates of relapse at 8 months for the 4 month treatment group (60%) versus the 12 month treatment group (41%). The median time to relapse was four months for the short treatment group versus 8 months for the long treatment group.

Patients who had more severe symptoms at study entry had a 2-fold greater chance of relapse over 8 months compared to those with lower symptom severity.  Additionally, patients with more severe symptoms were more likely to relapse over 8 months with short-term treatment (83%) versus long-term treatment (58%). This difference was not observed in the group of women with lower symptom severity.

A definitive recommendation about how long to continue SSRI treatment for a patient with PMS or PMDD cannot be made because of the limited research in this area. This study suggests, however, that relapse rates are relatively high among women who discontinue treatment with SSRI and that symptom severity should be considered when making decisions about how long to continue SSRI treatment in women with premenstrual syndromes.

Laura Petrillo, MD

Pearlstein T, Joliat MJ, Brown EB, Miner CM. Recurrence of symptoms of premenstrual dysphoric disorder after the cessation of luteal-phase fluoxetine treatment. Am J Obstet Gynecol 2003; 188(4):887-95.

Freeman EW, Rickels K, Sammel MD, Lin H, Sondheimer SJ. Time to relapse after short- or long-term treatment of severe premenstrual syndrome with sertraline. Arch Gen Psychiatry 2009; 66(5):537-44.