Serotonergic agents as an alternative to hormonal therapy for the treatment of menopausal vasomotor symptoms

Hot flashes represent one of the most common complaints among women undergoing menopause. Despite their prevalence, the pathophysiology leading to hot flashes is only partly understood. Short-term estrogen remains the most effective treatment for hot flashes, but because of safety concerns many women are reluctant to use this treatment. Several non-hormonal pharmacologic treatments have been evaluated in randomized, prospective clinical trials. Placebo-controlled clinical trials have suggested that agents from the selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) family reduce hot flashes by 50-60%. Successful treatment of hot flashes with these compounds may also be associated with improvements in sleep, mental health, and vitality. Adverse events may cause 10-20% of individuals to withdraw from treatment. The agents should be stopped with caution to prevent a discontinuation syndrome. Given the available data, the North American Menopause Society and the American College of Obstetricians and Gynecologists have recommended that women with moderate to severe, menopause-related hot flashes, with concerns or contraindications to estrogen-containing treatments, should consider prescription progestogens, venlafaxine, paroxetine, fluoxetine, or gabapentin. Prescribing clinicians are urged to discuss the potential benefits, adverse effects, and new information that may become available for each of the treatment options. Caution should also be exercised when prescribing strong cytochrome P450 2D6 inhibitors, such as paroxetine or fluoxetine, to women who are taking tamoxifen. Further studies are required to evaluate the optimal agent and duration of SSRI/SNRI treatment in menopausal women.