Antidepressant May Help With Premenstrual Syndrome

Fran Lowry

September 25, 2015

Administering the selective serotonin reuptake inhibitor (SSRI) sertraline (Zoloft, Pfizer Inc) at symptom onset may help relieve premenstrual dysphoric disorder (PMDD), particularly in women whose most pronounced symptom is irritability, new research suggests.

"Depending on the symptom scale, women with PMDD may or may not benefit from SSRI treatment during the interval from the onset of premenstrual symptoms through the first few days of menses," Kimberly A. Yonkers, MD, from Yale University School of Medicine, New Haven, Connecticut, told Medscape Medical News.

"We also found that women who stopped taking pills suddenly did not have discontinuation of symptoms," Dr Yonkers said.

The findings were published online September 9 in JAMA Psychiatry.

Confirming Anecdotal Experience

Dr Yonkers and her team previously published findings showing that women with PMDD did well when treated for one half of the menstrual cycle.

This prompted some clinicians to initiate this treatment at symptom onset only, without any evidence to support that management strategy.

"Therefore, we wanted to test whether this strategy would be effective, since preliminary studies have suggested that SSRI treatment can be shortened to the interval from symptom onset through the beginning of menses," she said.

The researchers randomly assigned 252 women with PMDD to receive either flexible-dose sertraline (50 to 100 mg/day; n = 125) or placebo (n = 127) at the start of their symptoms until the first few days of menses for six menstrual cycles.

The primary outcome measure was improvement on the Premenstrual Tension Scale (PMTS) score. On the PMTS, the score range is 0-36, with 36 indicating the most severe symptoms.

Secondary outcome measures included imrovement in scores on the Inventory of Depressive Symptomatology–Clinician Rated (IDS-C), which has a range of scores of 0-84, with 84 indicating the most severe symptoms; the Daily Record of Severity of Problems (DRSP) total and subscale scores, with higher scores indicating most severe problems; the Clinical Global Impression (CGI) scale; and the Michelson SSRI Withdrawal Symptoms Scale scores.

The mean PMTS scores at baseline for the women who received sertraline was 22.3 (standard deviation [SD], 4.8); for the women who received placebo, it was 21.4 (SD, 4.5).

The intent-to-treat analysis showed that by the end of the study period, the PMTS scores had declined to 11.7 (SD, 6.8) for the sertraline group, and to 12.0 (SD, 6.9) for the placebo group, for a group mean difference of 1.88 (95% confidence interval, 0.01 - 3.75; P = .06).

"The placebo response rate was substantial," Dr Yonkers noted.

Compared with the placebo group, women in the sertraline group showed greater improvement in IDS-C score (P = .02); total DRSP score (estimated mean difference, 1.09 points; 95% CI, 0.96 - 1.25, P = .02); and Anger/Irritability DRSP subscale score (1.22 points; 95% CI, 1.05 - 1.41; P<.01).

The women who received sertraline were also more likely to respond to treatment than the women who received placebo. In the sertraline group, 77 of 115 women (67.0%) responded, compared with 65 of 124 women (52.4%) in the placebo group.

The number of symptomatic days between symptom onset and the start of treatment shortened significantly for both groups. With sertraline, the mean change was -0.7 (SD, 3.4) days, and with placebo, the mean change was -1.0 (SD, 3.2).

There were no group differences in symptomatic days or in scores on the Michelson SSRI Withdrawal Symptoms Scale.

"Some studies have shown a risk of discontinuation symptoms even with relatively short periods of treatment, but this treatment period was too short to cause discontinuation and likely too short to cause some of the receptor changes that lead to discontinuation symptoms," Dr Yonkers noted.

For now, the advice physicians should give to patients hinges on patient preference and their treatment experience, she added.

"If someone has not responded to daily treatment, it is unlikely that intermittent treatment will be helpful. If this is a first time with pharmacotherapy, if a woman knows when symptoms begin and they reproducibly do so, intermittent treatment at symptom onset may be useful," Dr Yonkers said.

The study was sponsored by the National Institute of Mental Health. Dr Yonkers reports no relevant financial relationships.

JAMA Psychiatry. Published online September 9, 2015. Abstract

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