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Use of Antidepressant Associated with Reduction in Menopausal Hot Flashes

OAKLAND, Calif. – Peri-menopausal and post-menopausal women experienced a reduction in the frequency and severity of menopausal hot flashes with the use of the antidepressant medication escitalopram, compared to women who received placebo, according to a study in the January 19 issue of JAMA.

The Kaiser Permanente Division of Research in Oakland CA was one of four centers to participate in the eight-week randomized, double-blind trial that enrolled 205 women between July 2009 and June 2010.

“Hormonal agents have been the predominant therapy for menopausal hot flashes, but their use decreased substantially following the shifts in risk-benefit ratios that were identified in the Women’s Health Initiative Estrogen plus Progestin randomized controlled trial. However, no other treatments have U.S. Food and Drug Administration approval for menopausal hot flashes, and the efficacy of alternative pharmacologic and nonpharmacologic agents is inconclusive,” according to the study authors. Selective serotonin and serotonin norepinephrine reuptake inhibitors (SSRIs and SNRIs) have been investigated previously for hot flash treatment with mixed results. In two pilot investigations, the SSRI escitalopram reduced hot flashes with minimal toxicities but conclusions were limited by the small samples and un-blinded treatment.

Ellen W. Freeman, Ph.D., of the University of Pennsylvania School of Medicine, Philadelphia, and colleagues at four other centers across the nation — including the Kaiser Permanente Division of Resaerch in Oakland, CA — evaluated the effectivness of escitalopram vs. placebo to reduce the frequency and severity of hot flashes in healthy women. Researchers also examined whether race, menopausal status, depressed mood, and anxiety were important modifiers of any observed effect. Women received 10 to 20 mg/d of escitalopram or a matching placebo for 8 weeks. The primary outcomes included frequency and severity of hot flashes assessed by prospective daily diaries at weeks 4 and 8.

The average frequency of hot flashes at the beginning of the study was 9.8 per day. Escitalopram was associated with a significant reduction in the frequency of hot flashes relative to placebo, adjusted for race, site, and baseline hot flash frequency. In the escitalopram group, average hot flash frequency at week 8 decreased to 5.26 hot flashes per day (47 percent decrease or an average of 4.6 fewer hot flashes per day than at the beginning of the study). In the placebo group, hot flash frequency decreased to 6.43 hot flashes per day (33 percent decrease or an average of 3.2 fewer hot flashes per day).

Clinical improvement at week 8 (decrease of 50 percent or more from baseline in hot flash frequency) was significantly greater in the escitalopram group than in the placebo group (55 percent vs. 36 percent). Also, use of escitalopram significantly reduced hot flash severity compared with placebo, adjusted for race, site, and baseline severity.Race did not significantly modify the treatment effect. Overall discontinuation due to adverse events was 4 percent (7 in the active group, 2 in the placebo group).

“The 3-week post-intervention follow-up demonstrated that hot flashes increased after cessation of escitalopram but not after cessation of placebo, providing further evidence of escitalopram’s effects,” the authors write. The researchers note that although the decreases in hot flash frequency and severity appear modest, the study participants perceived these improvements as meaningful, as indicated by their reported satisfaction with treatment and desire to continue the treatment.

“The findings suggest that healthy women many benefit from escitalopram for non-hormonal release of menopausal hot flashes,” said Bette Caan, PhD, a research scientist and the Kaiser Permanente Division of Research and co-author of the study. Kaiser Permanente Division of  Research investigator Barbara Sternfeld, PhD, also a co-author of the study, emphasized that further studies are necessary to compare directly the effectiveness of  SSRIs and SNRIs with hormone therapy and to evaluate the effectiveness of non-pharmacologic, behavioral therapies, such as exercise, yoga, and omega 3 fatty acids.

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