Escitalopram Linked to Significant Reduction in Menopausal Hot Flashes

Kate Johnson

January 18, 2011

January 18, 2010 — Antidepressant therapy with the selective serotonin reuptake inhibitor escitalopram significantly reduced menopausal hot flash frequency and severity compared with placebo, according to the results of a new study published in the January 19 issue of the Journal of the American Medical Association.

The findings suggest "escitalopram provides a nonhormonal, off-label option that is effective and well tolerated in the management of menopausal hot flashes," lead study author Ellen W. Freeman, PhD, from the Departments of Obstetrics/Gynecology and Psychiatry at the University of Pennsylvania School of Medicine in Philadelphia, writes.

"This is particularly important for women who have risk factors for hormone therapy, although there are many other women who do not want hormone therapy because of its risks," Dr. Freeman told Medscape Medical News.

Dr. Ellen W. Freeman

Noting that comparisons with other studies must be viewed with caution, the study authors added that escitalopram's reduction in hot flash frequency relative to placebo "was only modestly less" than what has been reported for estrogen therapy.

The multicenter, randomized, double-blind, placebo-controlled trial included 205 women aged 40 through 62 years, who were either in the menopause transition (amenorrhea for 60 days or more in the past year) or postmenopausal (12 months or more since last menstrual period or bilateral oophorectomy).

Women with a hysterectomy and one or both ovaries remaining and who had follicle-stimulating hormone levels higher than 20 mIU/mL and estradiol levels of 50 pg/mL or less were also included.

Psychological exclusion criteria included a history of bipolar disorder or psychosis, a current major depressive episode, drug or alcohol abuse in the past year, and a suicide attempt in the past 3 years.

Women also had to be free of severe medical illness and had to meet hot flash criteria of at least 28 hot flashes or night sweats per week rated as bothersome or severe for 4 or more days per week.

Comparison to Estrogen Therapy

After completing 3 weeks of hot flash daily diaries, eligible women were randomly assigned to a daily 10-mg dose of escitalopram or placebo.

After 4 weeks, if the hot flash frequency was not reduced by 50%, and there was no decrease in severity, the dose was doubled for the next 4 weeks.

At 8 weeks, subjects taking 2 pills tapered their dose for a week, whereas subjects taking 1 pill stopped altogether.

The study's primary outcome was hot flash frequency and severity, and the secondary outcome was hot flash bother as recorded in daily diaries throughout the study.

Psychological measurements at baseline and at 4 and 8 weeks included the Patient Health Questionnaire domains of depression, as well as anxiety assessed by the General Anxiety Disorder questionnaire and the Hopkins Symptom Checklist.

The investigators found that escitalopram was associated with a significant reduction in the frequency, severity, and bother of hot flashes compared with placebo.

At baseline, the mean frequency of hot flashes for all subjects was 9.78 per day. At 8 weeks, the mean daily frequency decreased to 5.26 in the treatment group vs 6.43 in the placebo group.

This represented a mean reduction of 4.6 hot flashes (47%) per day in the treated group compared with a mean reduction of 3.2 (33%) hot flashes per day in the placebo group — a mean difference of 1.41 hot flashes per day between the groups.

In comparison, a meta-analysis of estrogen therapy compared with placebo showed between 2.4 and 3.2 fewer hot flashes per day with estrogen (JAMA. 2004;291:1610-1620), note the study authors.

Modest but 'Meaningful' Improvement

In terms of hot flash severity, rated from 1 to 3 as mild, moderate, or severe, the mean baseline score for all participants was 2.17.

At week 8, women in the treatment group had a mean score of 1.63 compared with a mean score of 1.89 in the placebo group. This represented a decrease in severity of 24% in the escitalopram group compared with 14% in the placebo group.

Escitalopram also significantly decreased hot flash bother. At baseline, the mean bother score was 3.14 on a 4-point scale.

By week 8, this was reduced to 2.48 in the treatment group compared with 2.76 in the placebo group. This represented a decrease of 20% in the treatment group compared with 18% in the placebo group.

"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 study authors write.

Race did not significantly modify the treatment effect.

Three weeks after the cessation of treatment the return of hot flashes was much more pronounced in women who had been taking escitalopram (mean difference, 1.59 flashes per day), "providing further indication of the escitalopram effect on hot flashes," they conclude.

"Selective serotonin and serotonin norepinephrine reuptake inhibitors (SSRIs and SNRIs) are the only treatments other than hormone therapy that have demonstrated efficacy for menopausal hot flashes," said Dr. Freeman. "A number of alternative treatments are being used, but none have demonstrated efficacy greater than placebo at this time."

The moderate placebo effect in the study also suggests "the importance of nondrug factors in clinical care and the potential for nonmedical approaches as other possible therapies for reduction of hot flashes," the study authors add.

'Enormous Interest' in Antidepressant Therapy

Commenting on the study Roger McIntyre, MD, associate professor of psychiatry and pharmacology at the University of Toronto, Ontario, Canada, and head of the Mood Disorders Psychopharmacology Unit there said, "There's categorically an enormous interest in this area...We know there are many mechanisms in the brain, the serotonergic system being one, that are implicated in depression but also implicated in the underlying biology of hot flashes.

"People are aware of the potential hazards of hormone-based interventions...everyone agrees that alternatives are needed," Dr. McIntyre added.

Although subjects' depression and anxiety scores were normal throughout the study, indicating no psychiatric illness, many women in the menopausal transition have concurrent hot flashes and depression, he said, making antidepressant therapy a particularly attractive option.

And in those without depression he wondered whether treatment of hot flashes using antidepressants might guard against future psychiatric risk.

"It's now well established that the menopausal transition is a risk period for depression, either new onset or recurrence. It's a period of psychiatric vulnerability for women in general, and if you can effectively treat hot flashes in a woman who is not currently depressed, will that treatment reduce her possibility of developing depression later on? I don't know."

Dr. Margery Gass

Margery Gass, MD, executive director of the North American Menopause Society in Mayfield Heights, Ohio, and consultant at the Cleveland Clinic Center for Specialized Women's Health, Cleveland, Ohio, said the efficacy of escitalopram and some other antidepressants in treating hot flashes brings some much-needed choice to women and physicians.

"I'd love to see a product like this get an official indication from the Food and Drug Administration," she said. "Anybody can prescribe [antidepressants] off-label, but there's still a lot of reluctance among patients to take anything that sounds like a psychiatric medication...so having that indication in print would be helpful."

However, for patients who want the most effective hot flash therapy estrogen remains the treatment of choice, she pointed out.

"It's very clear. With 8 to 12 weeks of hormone therapy you would very often see a 90% reduction in hot flashes."

Dr. Freeman reported research support and honoraria for consulting and presentations from Forest Laboratories Inc (makers of escitalopram), as well as financial arrangements with Wyeth, Pfizer, Xanodyne Pharmaceuticals, Pherin Pharmaceuticals and Bayer Health Care. Among her 14 other coauthors, 2 disclosed consulting or speaking honoraria or research support from Forest Laboratories as well as other companies and the rest reported no conflicts of interest. Dr. McIntyre does not receive any support from Forest Laboratories but he disclosed research grants, CME, advisory board and speakers bureau activity with multiple pharmaceutical companies. Dr. Gass has no personal arrangements with industry; however, NAMS receives unrestricted educational grants from multiple pharmaceutical companies. Forest Research Institute provided the drug and placebo but had no role in the design or conduct of the study, the collection, management, analysis and interpretation of the data, or the preparation of the manuscript.

JAMA. 2011;305:267-274. Abstract

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