Various selective serotonin reuptake inhibitors (SSRIs), including citalopram (Celexa), escitalopram (Lexapro) and paroxetine (Paxil), have been shown to be effective for the treatment of menopausal vasomotor symptoms (VMS). Other studies have supported the efficacy of the serotonin–norepinephrine reuptake inhibitors (SNRIs) duloxetine (Cymbalta) and venlafaxine (Effexor). The FDA recently approved a 7.5-mg formulation of paroxetine (marketed as Brisdelle) as the first non-hormonal treatment of hot flashes.

While multiple studies have clearly demonstrated that SSRIs and SNRIs reduce the frequency and severity of menopausal vasomotor symptoms, what we did not know is how these non-hormonal alternatives stacked up against the gold standard for the treatment of menopausal symptoms: estrogen replacement therapy.

A new study from the MsFLASH network suggests that the SNRI venlafaxine is as effective as estradiol for the treatment of vasomotor symptoms. 339 peri- and postmenopausal women with at least 2 bothersome VMS per day (mean, 8.1 per day) were randomized to treatment either with low-dose oral 17?-estradiol (0.5 mg/day) (n?=?97), low-dose venlafaxine extended release (75 mg/day) (n?=?96), or placebo (n?=?146) for 8 weeks.

Symptom frequency was reduced significantly more with estradiol (53%) and with venlafaxine (48%) than with placebo (29%). Treatment satisfaction was highest (70.3%) for estradiol and lowest (38.4%) for placebo, and intermediate (51.1%) for venlafaxine.

The researchers concluded that while the efficacy of estradiol may be slightly superior to that of venlafaxine, the difference appears to be small and may not be clinically relevant.

This study was funded by the NIH/NIA and is part of a series of clinical trials that is supported by funding from NIH through the MsFLASH network (Menopause Strategies: Finding Lasting Answers for Symptoms and Health). The Center for Women’s Mental Health is one of 6 research centers that comprise the MsFLASH network.

Ruta Nonacs, MD PhD

Joffe H, Guthrie KA, LaCroix AZ, et al. Low-Dose Estradiol and the Serotonin-Norepinephrine Reuptake Inhibitor Venlafaxine for Vasomotor Symptoms: A Randomized Clinical Trial. JAMA Intern Med. 2014 May 26.


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