Perimenopause is commonly defined as a time of hormonal fluctuation that typically occurs in women 40-55 years of age with changes in menstrual patterns. It has been demonstrated that women may be at particularly high risk for depressive symptoms during perimenopause due to declining levels of estrogen. In a previous study, women at risk for postpartum depression were found to benefit from estrogen replacement therapy. However, hormone replacement therapy (HRT) has become increasingly controversial in light of the findings of the Women's Health Initiative study that determined that women who received estrogen plus progestin were slightly more likely to suffer from coronary heart disease, strokes, blood clots in the lungs, and invasive breast cancer. Since the report of these results, HRT use has declined and as an alternative treatment for depression, antidepressants have been increasingly utilized for perimenopausal women. Fluoxetine, paroxetine, and venlafaxine are members of a new class of drugs called selective serotonin reuptake inhibitors (SSRIs) and which have all been demonstrated to be beneficial in the treatment of hot flashes. Recently, a new second-generation drug, Duloxetine (Cymbalta), has also been approved for the treatment of major depression. This drug is a member of a class of compounds that are referred to as serotonin-norepinephrine reuptake inhibitors (SNRIs). The method by which Duloxetine and members of this group achieve their effect is similar to that of the other antidepressant agents that have been used. Recent studies have indicated that Duloxetine appears to provide relief for both the mood and physical components of perimenopause.