Antidepressants in the treatment of menopausal hot flashes

In the menopausal transition, vasomotor symptoms, mainly hot flashes, are frequently reported. The latter affects 65% of women and represents one of the most prevalent symptoms. Within 4 to 5 years they usually resolve spontaneously, although 10% to 15% of women continue to suffer from them for several years. Sleep disturbances, reduced quality of life, and increased irritability associated with vasomotor symptoms motivate women to seek treatment.

Since hormone replacement therapy (HRT) reduces the frequency of vasomotor symptoms by 75%, it is the treatment of choice. However, it is not appropriate for all women, according to current evidence. For example, in women with endometrial or breast cancer, HRT is not recommended because it is associated with an increased risk of recurrence. There are many sites that explain HRT and one of them is

Caution is also needed in women who are at increased risk of thromboembolism, such as those who are obese, carriers of factor V Leiden mutations, and those with a history of venous thromboembolism. Although the risk of HRT is low in women between 50 and 59 years of age, the start of treatment in women over 60 years of age or its administration for a long time exposes them to greater risk. In this context, non-hormonal alternatives began to be evaluated for the treatment of vasomotor symptoms in women in the menopausal transition.

The physiological mechanism underlying hot flashes is not fully elucidated, but it is suggested that neuroendocrine changes occur during the menopausal transition that alters hypothalamic thermoregulation. The body responds to these changes through perspiration and vasodilation, which produces hot flashes. In addition, during this period the levels of estrogen and progesterone decrease, and it is suggested that the decrease in the former could be related to the appearance of hot flashes. The reduction in estrogen concentrations would result in a decrease in the production of endorphins, which would be associated with lower concentrations of norepinephrine and serotonin. The decrease in the concentration of these last two causes a positive regulation in their hypothalamic receptors, which would be linked to alterations in thermoregulation and the appearance of hot flashes.

Current evidence indicates that selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are effective in the treatment of hot flashes, as they increase systemic norepinephrine and serotonin concentrations.


A search of the Medline, CINAHL, and Cochrane Library databases was conducted to identify randomized controlled trials (RCTs) published between 2007 and 2012, that evaluated the efficacy and tolerability of SSRIs and SNRIs in perimenopausal and postmenopausal women with vasomotor symptoms. Information was extracted into 8 categories including study design, treatment, trial duration and site, number of participants, patient characteristics, outcomes, and adverse effects. In addition, methodological rigor was assessed using the Critical Appraisal Skills Program Questionnaire (CASP).


They identified 18 RCTs that evaluated perimenopausal or postmenopausal women with hot flashes, aged 27 to 78 years, and that met the inclusion criteria. The average number of hot flashes was between 46 and 76 hot flashes/week and the majority of the participants were Caucasian. Women taking psychoactive drugs, hormone therapy, antidepressants, chemotherapy, or radiation did not participate in the studies. Participants with active cancer at the time of treatment were also excluded, but patients with a history of breast cancer on stable doses of tamoxifen or aromatase inhibitors were allowed to be included. In all studies, the frequency and intensity of hot flashes were evaluated using a daily self-report.

Selective Serotonin Reuptake Inhibitors


Fluoxetine treatment was evaluated in 2 studies. One of them was a crossover trial conducted by Loprinzi et al. Fifty-one women were included and a 50% reduction in hot flash score was demonstrated in those treated with fluoxetine, compared to a 36% reduction in those who received placebo; however, this difference was not significant. Suvanto-Luukkonen and colleagues evaluated 150 women in a study that compared fluoxetine, citalopram, and placebo. Although all 3 groups demonstrated a significant reduction in hot flash frequency, the difference between the different regimens was also not significant.


Either hot flash frequency or composite scores were significantly decreased in all 3 studies evaluating paroxetine. Soares et al. conducted their study based on a cohort made up of 56 women. They observed a reduction in the hot flash frequency of 6.1/week and 2.8/week in patients treated with paroxetine and placebo, respectively. In 2003, Stearns et al evaluated 165 women and compared 2 treatment regimens with paroxetine versus placebo. They found reductions of 62% and 64% in patients who received 12.5 mg or 25 mg of paroxetine, respectively, versus 38% in those assigned to placebo. Finally, Stearns et al., in 2005, studied a cohort of 151 women and compared the administration of 10 mg or 20 mg of paroxetine against placebo. They observed reductions of 40.6% and 13.7% when comparing the 10 mg dose of paroxetine against placebo, while reductions were 51.7% and 26.6% when comparing the administration of 20 mg paroxetine against placebo. The only statistically significant adverse effect was nausea with the highest dose of paroxetine.


Treatment of hot flashes with sertraline was evaluated in 3 studies. One of them, carried out by Wu et al, included 46 women, while the other, carried out by Grady et al, had 99 participants. Neither found a significant difference in hot flash frequency or scores. In the third trial, Gordon and colleagues studied 97 women and found a modest effect of sertraline treatment compared to placebo.


Citalopram was shown to significantly reduce hot flash scores by 49% to 55%, compared with a 23% reduction seen in patients assigned to placebo, in a trial by Barton et al in a cohort of 254 women. No difference in adverse effects was observed between the groups, but there was a dropout rate of 20%, which was not analyzed by the authors. Another study carried out by Kalay and collaborators corroborated the efficacy of citalopram, without abandoning treatment due to adverse effects.

These antidepressants have been shown to play a role in the treatment of menopausal hot flashes and further studies are needed to understand how hormone-based therapy should be used to treat menopausal problems.