Phase II evaluation of desipramine for the treatment of hot flashes

Purpose: Newer antidepressants with serotonergic effects reduce hot flashes significantly better than placebo. This pilot study was designed to test the efficacy of desipramine, an older antidepressant targeting norepinephrine, in women desiring therapy for hot flashes and to evaluate the toxicity of desipramine. Patients and Methods: In this nonrandomized trial, eligible women were required to have reported ≥ 14 bothersome hot flashes per week for ≥ 1 month. After an initial baseline week in which no study medication was taken, participants started with desipramine 25 mg daily, which was titrated to 100 mg daily by week 5. The primary endpoint was change from baseline in hot flash frequency and hot flash score. Statistical methods involved paired t tests for continuous variables and Fisher exact tests for categoric variables. Results: Twenty-six patients were enrolled on this study between March 2004 and November 2005. The decrease in mean hot flash frequency over 4 weeks of treatment was 23%, with a 31% reduction in hot flash scores. Seven patients (30%) withdrew early because of toxicities consisting of insomnia, nausea, headaches, and/or feeling frightened. Conclusion: Desipramine did not reduce hot flashes beyond the 25%-30% reduction that would be expected with placebo, based on previous work. Therefore, data from this trial do not support further study of this agent for treatment of hot flashes. It is of physiologic interest that this older antidepressant, classified as a tricyclic, did not achieve a clinically significant reduction in hot flash scores in this pilot trial.