Low-dose Transdermal Testosterone Augmentation Therapy Improves Depression Severity in Women
Karen K. Miller, MD, Roy H. Perlis, MD, MSc, George I. Papakostas, MD, David Mischoulon, MD, PhD, Dan V. Iosifescu, MD, MSc, Danielle J. Brick, BA, and Maurizio Fava, MD
CNS Spectr. 2009;14(12):688-694
Background: Inadequate response to antidepressant monotherapy in women with major depressive disorder is common. Testosterone administration has been shown to be an effective augmentation therapy in depressed hypogonadal men with selective serotonin reuptake inhibitor-resistant depression. However, the effects of low-dose testosterone as augmentation therapy in women with treatment-resistant depression have not been studied.
Methods: Low-dose transdermal testosterone (300 mcg/day, Intrinsa, Procter and Gamble Pharmaceuticals) was administered to nine women with treatment-resistant depression in an 8 week open-label pilot protocol.
Results: There was a statistically significant improvement in mean Montgomery-Asberg Depression Rating Scale (MADRS) scores at 2 weeks, sustained through the 8 week period. Two-thirds of subjects achieved a response to the treatment (decrease in MADRS score of ≥50%) and 33% achieved remission (final MADRS score <10) after 8 weeks of therapy. Mean levels of fatigue, as measured by the MADRS lassitude item, significantly decreased at all time points with a mean 38% decrease from baseline to 8 weeks. Conclusion: These preliminary pilot data suggest that low-dose transdermal testosterone may be an effective augmentation therapy in women with treatment-resistant depression. Further studies are warranted.
———-
After completion of the baseline visit, each participant received transdermal testosterone 300 mcg (Intrinsa, Procter & Gamble Pharmaceuticals, Cincinnati, OH), in the form of one 300 mcg patch placed on the abdomen and changed twice weekly. This dose is at the higher end of the estimates of mean daily testosterone production for healthy non-hirsute women, ~100–300 mcg daily.
From my point of view, the women with major depressive disorder generally had very low baseline total testosterone levels of 14.7 +- 6.5 ng/dL. This improves response to testosterone.
The mean serum testosterone concentration at baseline was 14.7±6.5 ng/dl, with an increase to 69.7±57.3 ng/dl at 8 weeks (P=.012)
The mean increase in testosterone with treatment is to what I consider a good level (between 50-75 ng/dL). Note, however, that there is very high variability in the increase in total teststerone (the SD is +- 57.3 ng/dL). Thus, some women may experience no absorption of testosterone and some may have an excessive amount of testosterone. This may reduce the overall effectiveness of treatment. Lack of absorption may mean there is myxedema present due to suboptimal thyroid hormone (another pathophysiologic contributor to major depressive disorder). Excessive absorption may increase estradiol and lower free thyroid hormone levels, limiting response to treatment in some women, particularly those who already have adequate estrogen levels.
The women were already on SNRI or SSRI treatment with only partial response – i.e. treatment resistance. This is understandable since SNRI and SSRI treatment only treats part of the pathophysiology of major depressive disorder.