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Low-Dose Testosterone Augmentation for Antidepressant-Resistant Major Depressive Disorder in Women: An 8-Week
Laura E Dichtel1, Linda L Carpenter1, Maren Nyer1
1Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston (Dichtel, Kimball, Miller); Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston (Nyer, Mischoulon, Deckersbach, Dougherty, Yeung, Cassano, Hahn, Farabaugh, Pedrelli, Trinh, Dording, Cusin, Papakostas, Chang, Fisher, Shapero, Chen, Fava); Department of Psychiatry, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston (Brady); Biostatistics Center, Massachusetts General Hospital, Boston (Schoenfeld); Butler Hospital and Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Medicine, Brown University, Providence, R.I. (Carpenter, Tyrka, Price); Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston (Rao); Mayo Clinic Endocrine Laboratory, Rochester, Minn. (Singh).
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.
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