Phase III Evaluation of Fluoxetine for Treatment of Hot Flashes

Abstract

PURPOSE: Hot flashes can be a prominent problem in women with a history of breast cancer. Given concerns regarding the use of hormonal therapies in such patients, other nonhormonal means for treating hot flashes are required. Based on anecdotal information regarding the efficacy of fluoxetine and other newer antidepressants for treating hot flashes, the present trial was developed. PATIENTS AND METHODS: This trial used a double-blinded, randomized, two-period (4 weeks per period), cross-over methodology to study the efficacy of fluoxetine (20 mg/d) for treating hot flashes in women with a history of breast cancer or a concern regarding the use of estrogen (because of breast cancer risk). Eligible patients had to have reported that they averaged at least 14 hot flashes per week; they could have received tamoxifen or raloxifene as long as they were on a stable dose. The major outcome measure was a bivariate construct representing hot flash frequency and hot flash score, analyzed by a classic sums and differences cross-over analysis. RESULTS: Eighty-one randomized women began protocol therapy. By the end of the first treatment period, hot flash scores (frequency × average severity) decreased 50% in the fluoxetine arm versus 36% in the placebo arm. Cross-over analysis demonstrated a significantly greater marked hot flash score improvement with fluoxetine than placebo (P = .02). The results were not adjusted for potential confounding influences, including age and tamoxifen use. The fluoxetine was well tolerated. CONCLUSION: This dose of fluoxetine resulted in a modest improvement in hot flashes.