Although estrogen has long been the gold standard for treating the hot flashes and night sweats of menopause, some women are unable or unwilling to use it because of associated risks. Consequently, SSRI or SNRI antidepressants—particularly the SNRI antidepressant venlafaxine—are often prescribed as a treatment for these vasomotor symptoms.
However, while SSRI and SNRI antidepressants have been found to be more effective than placebo in countering hot flashes and night sweats, their effectiveness compared with estrogen has not been studied. Hadine Joffe, M.D., an associate professor of psychiatry at Harvard Medical School, and her colleagues conducted a study to evaluate the two types of medications, using venlafaxine as the test antidepressant.
As they reported May 26 in JAMA Internal Medicine, both estrogen and venlafaxine were significantly more effective than a placebo, but estrogen was slightly more effective than venlafaxine.
A total of 339 perimenopausal and postmenopausal women with at least two bothersome vasomotor symptoms a day—on average, eight a day—took part in the study. The researchers excluded candidates who had experienced major depressive episodes within the previous year.
The subjects were randomized to receive either low-dose oral estradiol (0.5 mg/d), low-dose venlafaxine extended release (75 mg/d), or a placebo for eight weeks. The researchers used low-dose rather than high-dose estradiol, they explained, “because of recommendations to use the lowest effective estrogen therapy dosage.”
Throughout treatment, and on a daily basis, the subjects recorded in diaries how often they experienced vasomotor symptoms.
By the end of treatment, the estradiol group was experiencing 3.9 vasomotor episodes a day on average, the venlafaxine group 4.4., and the placebo group 5.5. Estrogen reduced the frequency of vasomotor episodes by 53 percent, venlafaxine by 48 percent, and placebo by 29 percent. The differences between the estradiol group and the placebo group, as well as between the venlafaxine group and placebo group, were statistically significant. The differences between the venlafaxine group and the estradiol group were not.
Tolerability of both estradiol and venlafaxine was high. Discontinuation because of adverse events was uncommon and did not differ significantly between treatments.
The researchers also found that the treatment responses were not influenced by subjects’ mood symptoms, sleep quality, or race. A third of the subjects were African American.
“It is nice to see this head-to-head study comparing estradiol and venlafaxine in the treatment of menopausal hot flashes,” Claudia Reardon, M.D., an assistant professor of psychiatry at the University of Wisconsin and an expert on women’s health issues, said in an interview with Psychiatric News. “While venlafaxine may not be quite as effective as estradiol in the treatment of these symptoms, it does appear to work notably better than placebo. Our women patients often talk to us as their mental health providers about their bothersome menopausal symptoms, and this study helps us to be able to discuss the likely relative efficacy of their options with them.”
“The results of this carefully conducted study provide women and their physicians with critical data to guide treatment for vasomotor symptoms . . . , which affect the lives of the majority of midlife women,” Katherine Wisner, M.D., a professor of psychiatry and obstetrics and gynecology at Northwestern University, told Psychiatric News.
“Although a number of studies have demonstrated the efficacy of venlafaxine and other serotonergic antidepressants for treating vasomotor symptoms, this study advances our knowledge by comparing estradiol and venlafaxine to placebo within the same study,” Laura Miller, M.D., medical director of women’s mental health at the Edward Hines Jr. VA Hospital in Illinois, said. “The findings confirm that both estradiol and venlafaxine reduce the frequency, severity, and interference of menopausal hot flashes. While supporting prior impressions that the impact of estradiol on vasomotor symptoms is greater than that of venlafaxine, it shows that the magnitude of difference is relatively small. Caveats are that this study is not a direct comparison between estradiol and venlafaxine (both were compared with placebo) and that medroxyprogesterone was not given during the study as it would be with clinical use of estrogen (it was given only after unblinding). [But] overall, the study adds valuable information about an alternative to estrogen for the treatment of bothersome menopausal vasomotor symptoms.”
The study was funded by the National Institutes of Health. ■