Background: Menopausal hot flashes can be treated effectively with estrogen and progesterone, but concerns about the risks of hormonal treatment have greatly curtailed their use. Currently, there are no other treatments for hot flashes approved by the U.S. Food and Drug Administration, and studies of other agents, including selective serotonin and serotonin-norepinephrine reuptake inhibitors, have shown varied results. Freeman and colleagues studied the effectiveness of escitalopram (Lexapro) on the frequency, severity, and bother of hot flashes in menopausal women.
The Study: This multicenter, randomized, placebo-controlled study recruited healthy perimenopausal or postmenopausal women between 40 and 62 years of age. Women who reported frequent hot flashes (at least 28 hot flashes or night sweats per week that did not decrease significantly between weeks 1 and 3) that were rated as bothersome or severe at least four days a week were eligible to participate. Exclusion criteria included current or recent use (within the past 30 days) of psychotropic medication or any other prescription, over-the-counter, or herbal remedy for hot flashes; use of hormonal therapies or contraception, selective estrogen receptor modulators, or aromatase inhibitors in the past two months; and severe medical or mental illness. Menopausal and general health status were assessed before randomization at two clinic visits with a history and symptom diary review, physical examination, and laboratory testing.
Participants were randomized to receive 10 mg of escitalopram or placebo for eight weeks. If the frequency of hot flashes did not decrease by at least 50 percent or the severity did not decrease after four weeks, the dosage was increased to two tablets per day. Participants continued recording hot flash frequency, severity, and bother during the course of the trial. Women taking two tablets per day at the end of eight weeks tapered the dose over a week, and persons taking one tablet stopped at eight weeks. Adherence and adverse effects were assessed through a telephone interview one week after randomization and at clinic visits at weeks 4 and 8. A final telephone interview was conducted at week 11 to assess return of symptoms, adverse events, or withdrawal symptoms.
Results: The primary outcomes were hot flash frequency and severity (expressed as the seven-day mean) at weeks 4 and 8. Frequency was calculated as the number of hot flashes or night sweats over 24 hours. Severity was rated as mild, moderate, or severe. Secondary outcomes included hot flash bother (none, a little, moderately, a lot) and clinical improvement from baseline (a decrease in hot flash frequency of at least 50 percent). A decrease in hot flash frequency of at least 75 percent was also evaluated. Linear regression modeling accounted for any differences among race, and any effect of baseline depressed mood or anxiety.
A total of 104 women were randomized to receive escitalopram and 101 were randomized to receive placebo. In both groups, the baseline hot flash frequency was 9.78 per day. By the fourth week, 51 percent of the escitalopram group and 70 percent of the placebo group increased their dosage to two tablets per day because of the lack of symptom improvement. By week 8, women in the escitalopram group had a significant decrease in hot flash frequency compared with placebo (4.60 fewer per day compared with 3.20 fewer), and hot flash severity and bother were significantly decreased in the escitalopram group compared with placebo. A decrease in hot flash frequency of at least 50 percent from baseline was achieved in 55 percent of the treatment group versus 36 percent of the placebo group. Similarly, a decrease of at least 75 percent from baseline was achieved in 19 percent of the treatment group versus 9 percent of the placebo group. Race, depressed mood, or anxiety did not significantly modify the treatment effect. Adverse effects in both groups were similar. At the 11-week follow-up, women in both groups reported increasing frequency of hot flashes, but the increase was higher in the escitalopram group than in the placebo group. Severity and bother ratings also increased in the escitalopram group but not in the placebo group at week 11. When asked if they would like to continue their assigned medication, 64 percent of women in the escitalopram group said they would, compared with 42 percent in the placebo group.
Conclusion: Although the placebo effect is expected in hot flash studies and was moderate in this study, escitalopram at a dosage of 10 or 20 mg per day effectively reduces hot flash frequency, severity, and bother compared with placebo.