Vasomotor Symptoms Relieved by Escitalopram, E2, Venlafaxine

Troy Brown, RN

July 15, 2015

Menopausal women with moderate vasomotor symptoms may find relief from escitalopram, low-dose dose oral 17-beta-estradiol (E2), or venlafaxine, according to a pooled analysis of individual-level data from three randomized clinical trials that tested drug and nondrug interventions. Not everyone is convinced the pooled analysis works, however.

"A single trial designed to provide direct head-to-head comparisons of all six interventions would have required considerably larger samples sizes that were not possible within time and cost constraints. Furthermore, intervention-specific exclusion criteria and women's preferences would have made recruitment to a single trial testing all interventions impractical," the researchers write. "The analyses presented here bridge the gap between the feasible, individual trials and an idealistic trial providing direct comparisons."

Katherine A. Guthrie, PhD, from the MsFLASH Data Coordinating Center, Fred Hutchinson Cancer Research Center, the Group Health Research Institute, and the University of Washington School of Medicine, Seattle, and colleagues present their findings in an article published online July 8 in Obstetrics & Gynecology.

Although all three trials were conducted by the same group, The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network, the authors note that there were design differences that made comparing results across interventions difficult. "This article addresses that issue with a novel comparative effectiveness analysis that pools each trial's individual-level data and adjusts for differences between studies," they write.

The trials included 899 perimenopausal and postmenopausal women with 14 or more bothersome vasomotor symptoms per week. The study interventions included 10 to 20 mg escitalopram per day, nonaerobic yoga, aerobic exercise, 1.8 g per day omega-3 fatty acid supplementation, 0.5 mg low-dose E2 per day, and 75 mg low-dose venlafaxine extended release per day.

Primary outcome measures were changes from baseline in mean frequency of daily vasomotor symptoms and bother during 8 to 12 weeks of treatment. The researchers used linear regression models to estimate differences in outcomes between intervention and corresponding control groups in each study, adjusted for baseline characteristics.

At 8 weeks, reduction of vasomotor symptom frequency from baseline relative to placebo was comparable for escitalopram, at −1.4 per day (95% confidence interval [CI], −2.7 to −0.2); low-dose E2, at −2.4 (95% CI, −3.4 to −1.3); and venlafaxine, at −1.8 (95% CI, −2.8 to −0.8). The reduction in vasomotor symptom bother was small, with no variation across the three pharmacologic treatments (mean, −0.2 to −0.3, relative to placebo).

However, the researchers found no significant effects on vasomotor symptom frequency or bother with aerobic exercise, yoga, or omega-3 supplements.

"These data suggest use of escitalopram, oral low-dose E2, or low-dose venlafaxine based on individual risk profiles and side effect concerns is a reasonable starting point for treating women with bothersome hot flushes" the authors conclude.

At least one researcher, however, has reservations about the methods. "I find this paper somewhat confusing, using fancy statistics to merge and compare three rather second-rate trials. I say the latter because the key qualification for volunteer acceptance was at least 14 bothersome symptoms per week," said Wulf Utian, MD, PhD, DSc, executive director, North American Menopause Society, and professor emeritus, Case Western Reserve University, Cleveland, Ohio. "[That] is an extremely low number compared to the [US Food and Drug Administration] guidance for [vasomotor symptom] trials requiring more than 56 moderate to severe hot flashes per week, with efficacy required at 4 weeks and maintained through 12 weeks. Two of the three trials merged in this paper were only 8 weeks in duration," he told Medscape Medical News.

"Also, it is very difficult to directly compare placebo effect, which seemed quite close to most of the products tested, and there was a correction factor to exclude high placebo responses from the analysis." Dr. Utian explained.

"There are other problems. Study 1 increased drug dose if effect was less than 50%. Study 3 increased the venlafaxine dose, but not the low-dose estradiol," Dr. Utian noted.

Given all the data available, Dr Utian concluded, "Unless there is a contradiction, estrogen is the first and best choice for [vasomotor symptom] relief. [Selective serotonin reuptake inhibitor] offers a lower efficacy and is only second choice."

One author is a consultant on a Data Monitoring Committee for Merck Sharpe & Dohme. One author reports grant funding from Cephalon/Teva, has been a consultant for Noven Pharmaceuticals and Merck, and has served on an advisory board for Merck. One author reports research funding from Bayer Pharmaceuticals. One author reports research support from AstraZeneca, Bristol-Myers Squibb/Otsuka, Cephalon Inc, Ortho-McNeil Janssen, Sunovion Pharmaceuticals Inc, and Takeda/Lundbeck. One author reports grants paid to the University of Pennsylvania by Forest Laboratories Inc and Bionovo. Dr Guthrie and the remaining authors have disclosed no relevant financial relationships.

Obstet Gynecol. Published online July 8, 2015. Abstract


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