Study on Transdermal Testosterone and Antidepressant-Resistant Major Depressive Disorder

Delhi: Adjunctive transdermal testosterone had no benefit over placebo in improving depression symptoms, sexual dysfunction, or fatigue in women with antidepressant-resistant major depressive disorder (MDD), suggests a recent study. The findings are published in the American Journal of Psychiatry.

In small studies, low-dose testosterone has been shown to improve sexual function, fatigue, and depression symptom severity in women not formally diagnosed with MDD. Laura E. Dichtel and colleagues sought to determine whether adjunctive low-dose transdermal testosterone helps in improving depression symptom severity, fatigue, and sexual function in women with antidepressant-resistant MDD. A substudy of functional MRI (fMRI) examined effects on activity in the anterior cingulate cortex (ACC) -- a brain region involved in mood regulation.

For the purpose, the researchers conducted an 8-week randomized double-blind placebo-controlled trial of adjunctive testosterone cream. It involved 101 women, ages 21–70 [mean age 47 years; mean baseline MADRS score was 26.6 (SD=5.9)], with antidepressant-resistant major depression. Eighty-seven (86%) participants completed 8 weeks of treatment.

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 a change in ACC activity.

Key Findings of the Study

• MADRS scores decreased in both study arms from baseline to week 8 (testosterone arm: from 26.8 to 15.3; placebo arm: from 26.3 to 14.4), 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.

"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," concluded the authors.

"Low-Dose Testosterone Augmentation for Antidepressant-Resistant Major Depressive Disorder in Women: An 8-Week Randomized Placebo-Controlled Study," is published in the American Journal of Psychiatry.

DOI: https://ajp.psychiatryonline.org/doi/abs/10.1176/appi.ajp.2020.19080844