Low-Dose Testosterone Augmentation for Antidepressant-Resistant Major Depressive Disorder in Women: An 8-Week Randomized Placebo-Controlled Study
Year: 2020
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: OBJECTIVE: Low-dose testosterone has been shown to improve depression symptom severity, fatigue, and sexual function in small studies in women not formally diagnosed with major depressive disorder. The authors sought to determine whether adjunctive low-dose transdermal testosterone improves depression symptom severity, fatigue, and sexual function in women with antidepressant-resistant major depression. A functional MRI (fMRI) substudy examined effects on activity in the anterior cingulate cortex (ACC), a brain region important in mood regulation. METHODS: The authors conducted an 8-week randomized double-blind placebo-controlled trial of adjunctive testosterone cream in 101 women, ages 21-70, with antidepressant-resistant major depression. The primary outcome measure was depression symptom severity as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary endpoints included fatigue, sexual function, and safety measures. The primary outcome of the fMRI substudy (N=20) was change in ACC activity. RESULTS: The participants' mean age was 47 years (SD=14) and their mean baseline MADRS score was 26.6 (SD=5.9). Eighty-seven (86%) participants completed 8 weeks of treatment. MADRS scores decreased in both study arms from baseline to week 8 (testosterone arm: from 26.8 [SD=6.3] to 15.3 [SD=9.6]; placebo arm: from 26.3 [SD=5.4] to 14.4 [SD=9.3]), with no significant difference between groups. Improvement in fatigue and sexual function did not differ between groups, nor did side effects. fMRI results showed a relationship between ACC activation and androgen levels before treatment but no difference in ACC activation with testosterone compared with placebo. CONCLUSIONS: Adjunctive transdermal testosterone, although well tolerated, was not more effective than placebo in improving symptoms of depression, fatigue, or sexual dysfunction. Imaging in a subset of participants demonstrated that testosterone did not result in greater activation of the ACC.
Source: American Journal of Psychiatry
Authors: Laura E. Dichtel, Linda L. Carpenter, Maren Nyer, David Mischoulon, Allison Kimball, Thilo Deckersbach, Darin D. Dougherty, David A. Schoenfeld, Lauren Fisher, Cristina Cusin, Christina Dording, Nhi-Ha Trinh, Paola Pedrelli, Albert Yeung, Amy Farabaugh, George I. Papakostas, Trina Chang, Benjamin G. Shapero, Justin Chen, Paolo Cassano, Emily M. Hahn, Elizabeth M. Rao, Roscoe O. Brady, Ravinder J. Singh, Audrey R. Tyrka, Lawrence H. Price, Maurizio Fava, Karen K. Miller
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1020569705, 1/2-Collaborative Study: Testosterone Antidepressant Augmentation in Women, The Growth Hormone and Insulin-like Growth Factor-1 Axis in Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis, 2/2 Collaborative Study: Testosterone Augmentation in Women, Growth Hormone and Cardiovascular Disease, Adapted Cognitive Behavioral Treatment for Depression in Patients with Moderate to Severe Traumatic Brain Injury, Mechanisms of Hyperthermic Yoga for the Treatment of Depression, G8990172276, Training Program in Endocrinology
OpenAlex ID: W3042816308