Duloxetine for Perimenopausal Depression

Over twenty percent of women will experience a major depressive episode in their lifetimes, a prevalence that reflects a greater risk than is found among men. Perimenopausal depression, postpartum depression, and unpleasant, disturbing emotional and physical symptoms that occur just before monthly menstrual periods have been shown to occur during times of fluctuating levels of estrogen and other gonadal hormones.

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.

In order to continue studying the benefits of Duloxetine in subjects with perimenopause, this study is designed to enroll 20 perimenopausal women with depression in a 9-week trial. Subjects cannot be enrolled in the study if they are currently using hormone replacement therapy and all patients must meet the criteria for a major depressive episode, which will be verified by the standardized protocol for establishing depression, the Structured Clinical Interview for DSM-IV (SCID).

Subjects enrolled in the study, will undergo 7 total clinic visits during a 9-week study period. The first visit will last approximately 3 hours with all other visits taking approximately 45 minutes. During the 1st visit, medical and psychiatric history will be reviewed and blood will be drawn (approximately 3 teaspoons). Blood will be used for routine laboratory testing. Urine will also be collected for a pregnancy test.

For Major Depressive Disorder, the FDA has recommended that a total dose of 40 mg/day (20 mg taken twice a day) to 60 mg/day (given either once a day or as 30 mg twice a day) be administered without regard to meals. While a 120 mg/day dose has been shown to be safe and effective, there is no evidence that doses higher than 60 mg confer additional significant benefit, and the higher dose is clearly less well tolerated. During the current study, for a short period of time participants will receive a placebo (a pill that looks like the study drug but which does not contain any medication), although during the majority of the study, participants will be receiving the actual study medication (Duloxetine). The initial dose of Duloxetine to be given will be a 30 mg dose with the dosage increased over time to 60 mg per day. This study will be blinded, meaning that participants will not know whether they are taking placebo or the study drug. However, all subjects will receive duloxetine for the majority of the time they are enrolled in the trial. Investigators will know when subjects are receiving the placebo but in order to maintain the blinding of this study, the study staff will not be able to tell participants when they are taking placebo and when they are taking Duloxetine.