Hormonal therapy can be an effective preventive therapy for reducing hot flashes. But because of reports about the potential harmful effects of using hormones – invasive breast cancer, stroke, coronary artery disease and blood clots – many women and their doctors have avoided the therapy. Unfortunately, this left only alternative medical treatments and over-the-counter medications to combat unpleasant menopause side effects.

Paroxetine contains a lower dose of the same medication found in the psychiatric drugs paroxetine hydrochloride (Paxil) and paroxetine mesylate (Pexeva) for the treatment of depression. The menopause drug is taken in the evening, while the antidepressants are taken in the morning.

Two controlled clinical trials established the effectiveness of paroxetine. Nearly 1,200 menopausal women who had an average of 10 moderate-to-severe hot flashes a day obtained moderate relief, compared to those who took a placebo for 12 weeks. In one study, there were 6 fewer hot flashes per day on average with paroxetine, compared to 5 with the placebo. Perhaps most importantly, women on paroxetine considered the fewer hot flashes to be significant compared to the placebo.

Despite these study results, the FDA Reproductive Health Drugs Advisory Committee concluded by a vote of 10 to 4 that the overall benefits of paroxetine did not support approval. According to an article published in the New England Journal of Medicine – from the FDA's Center for Drug Evaluation and Research – there were 3 main reasons for rejecting paroxetine for the treatment of menopausal symptoms:

1. Only modest improvements in menopausal symptoms, compared to the placebo.
While the clinical trials may have shown only modest, but still statistically significant, benefits from paroxetine, the women themselves found the relief gained to be significant.