Clinical Question

Are selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) more effective for the treatment of vasomotor symptoms of menopause?

Evidence-Based Answer

Both SSRIs and SNRIs are effective at relieving vasomotor symptoms of menopause. (Strength of Recommendation [SOR]: A, systematic reviews.) No studies have directly compared the two classes of medication. SNRIs are associated with more adverse effects. Venlafaxine is preferred in women with breast cancer because SSRIs may interfere with tamoxifen metabolism. (SOR: C, expert opinion.)

Evidence Summary

A 2015 systematic review of 18 randomized controlled trials (RCTs) involving women 27 to 78 years of age (N = 3,490) evaluated the effectiveness of SSRIs and SNRIs for the treatment of vasomotor symptoms in menopause.¹ Study participants reported 0 to 50 hot flashes per week. Several studies included women with a history of cancer and stable selective estrogen receptor modulator use, but patients with active cancer were excluded. Patients using hormone therapy, antidepressants, and psychoactive drugs were also excluded. All studies evaluated vasomotor symptom frequency, measured as times per week, and average severity, rated on a scale of 0 to 4 (with 4 being the most severe). These measures were then multiplied to produce a composite score, with higher scores indicating more severe symptoms. Venlafaxine (37.5 mg) was identified as a first-line agent in the SNRI class. It showed the fastest onset of symptom relief (41% reduction alone by one week, 26% reduction vs. placebo; P < .001) but also more frequent adverse effects such as nausea, dry mouth, and constipation. The SSRI paroxetine (Paxil) showed the greatest overall reduction in hot flashes (40.6% at 10 mg and 51.7% at 20 mg; P = .0006 and P = .002, respectively) across both classes when compared with placebo. Additional SSRI and SNRI studies are described in eTable A. Limitations of this review included a primarily White population and multiple scales used to assess patient response.