Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression

Context: Alternative and over-the-counter medicines have become increasingly popular choices for many patients who prefer not to take traditional antidepressants. The adrenal androgen and neurosteroid dehydroepiandrosterone (DHEA) is available as over-the counter hormonal therapy and previously has been reported to have antidepressant-like effects. Objective: To evaluate the efficacy of DHEA as a mono-therapy treatment for midlife-onset depression. Design: A double-blind, randomized, placebo controlled, crossover treatment study was performed from January 4, 1996, through August 31, 2002. Settings: The National Institute of Mental Health Midlife Outpatient Clinic in the National Institutes of Health Clinical Center, Bethesda, Md. Patients: Men (n = 23) and women (n = 23) aged 45 to 65 years with midlife-onset major or minor depression participated in this study. None of the subjects received concurrent antidepressant medications. Intervention: Six weeks of DHEA therapy, 90 mg/d for 3 weeks and 450 mg/d for 3 weeks, and 6 weeks of placebo. Main Outcome Measures: The 17-Item Hamilton Depression Rating Scale and Center for Epidermologic Studies Depression Scale. Additional measures included the Derogatis Interview for Sexual Functioning. Results were analyzed by means of repeated-measures analysis of variance and post hoc Bonferroni t tests. Results: Six weeks of DHEA administration was associated with a significant improvement in the 17-Item Hamilton Depression Rating Scale and the Center for Epidemiologic Studies Depression Scale ratings compared with both baseline (P<.01) and 6 weeks of placebo treatment (P<.01). A 50% or greater reduction in baseline Hamilton Depression Rating Scale scores was observed in 23 subjects after DHEA and in 13 subjects after placebo treatments. Six weeks of DHEA treatment also was associated with significant improvements in Derogatis Interview for Sexual Functioning scores relative to baseline and placebo conditions. Conclusion: We find DHEA to be an effective treatment for midlife-onset major and minor depression.