This study demonstrated that escitalopram, 10–20 mg/day, is effective for treatment of hot flashes in menopausal women. Fifty-five percent of women in the escitalopram group (versus 36% in the placebo group) reported decreases in hot flash frequency of 50% or more, a standard clinical indicator of improvement. Decreases in the severity and bother of hot flashes were also significant and paralleled the decreases in hot flash frequency. When participants stopped escitalopram, hot flash symptoms rapidly worsened.
The study is the first to show efficacy of escitalopram over placebo for menopausal hot flashes. It extends the results of other SSRI and SNRI trials for hot flash treatment,11–20
and confirms a small pilot study of escitalopram as an effective treatment for hot flashes.35
Notably, women who were not
depressed or anxious responded swiftly to escitalopram, with significantly greater improvement compared to placebo after one week of treatment. Although the precise mechanism is unknown, the rapid improvement and demonstrated efficacy in non-depressed women suggest that the mechanism may differ from the action of SSRIs/SNRIs in psychiatric conditions. Evidence indicates that estrogen is strongly involved in the serotonergic system, supporting postulates of the role of serotonin receptors in the pathogenesis of hot flashes.36
Meta-analyses of previous trials of SSRIs/SNRIs concluded that serotonergic agents are effective for women with breast cancer, many of whom were concurrently treated with tamoxifen, but there was insufficient evidence for these medications in naturally postmenopausal women.8
The present study confirms that escitalopram is an efficacious treatment for hot flashes in menopausal women without
other severe illness or co-therapy and could be considered a first-line agent for these women.
An important consideration for all menopausal therapies is medication tolerance and side effect profile. While a majority reported common side effects of escitalopram after initiating treatment, there were no serious AEs and only 7 women on escitalopram stopped due to AEs. Forty-four percent improved at the starting dose (10 mg/day). Another 11% who were unimproved after 4 weeks improved with a single dose increase to 20 mg/day. Although response to the initial dose might continue to increase with time, a dose increase is a reasonable option, based on the evidence that it was well-tolerated and promoted improvement for some women.
To our knowledge, this is the first clinical trial to examine whether there are racial differences in response to SSRI treatment for hot flashes. Some but not all reports indicate that more African American than white women report hot flashes,23–25, 37–40
but race had no significant effect on the response to escitalopram in the present study.
Limitations of the study should be considered. Although an 8-week treatment interval is brief, other data indicate that this interval is sufficient to determine long-term efficacy of a non-hormonal compound.41, 42 We selected potential modulating factors of treatment response based on previous reports and the aims of this study, but other factors associated with treatment response likely exist. This was a randomized, community-based sample, but the participants may be a select group who were motivated to seek treatment. The findings are from urban, healthy, African American and white menopausal women and may not be generalizable to other geographic, racial or clinical groups.
Strengths of this study include the prospective assessment of hot flashes, which were reported on daily diaries throughout the study, and a very low dropout rate, with 95% providing response data at week 8. Three screening weeks of daily hot flash reports and clear criteria for hot flash frequency and severity provided a stable baseline that contributed to the high continuation rate and a relatively moderate placebo response. The 3-week follow-up after stopping treatment showed that hot flashes returned swiftly in the escitalopram group but not the placebo group, providing further evidence of the drug's effect in reducing hot flashes.
These findings indicate that escitalopram provides an off-label non-hormonal option that is effective and well-tolerated for management of menopausal hot flashes in healthy women. Further studies are needed to directly compare the relative efficacy of SSRIs/SNRIs with hormone therapy in hot flash management.