Hostname: page-component-78c5997874-m6dg7 Total loading time: 0 Render date: 2024-11-19T05:29:24.920Z Has data issue: false hasContentIssue false

Low-dose Transdermal Testosterone Augmentation Therapy Improves Depression Severity in Women

Published online by Cambridge University Press:  07 November 2014

Abstract

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.

Type
Original Research
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Kessler, RC, Berglund, P, Demler, O, Jin, R, Merikangas, KR, Walters, EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62:593602.Google Scholar
2.Trivedi, MH, Rush, AJ, Wisniewski, SR, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006;163:2840.Google Scholar
3.Fava, M. Symptoms of fatigue and cognitive/executive dysfunction in major depressive disorder before and after antidepressant treatment. J Clin Psychiatry. 2003;64(Suppl 14):3034.Google Scholar
4.Nierenberg, AA, Keefe, BR, Leslie, VC, et al. Residual symptoms in depressed patients who respond acutely to fluoxetine. J Clin Psychiatry. 1999;60:221225.CrossRefGoogle ScholarPubMed
5.Pope, HG Jr, Cohane, GH, Kanayama, G, Siegel, AJ, Hudson, JI. Testosterone Gel Supplementation for Men With Refractory Depression: A Randomized, Placebo-Controlled Trial. Am J Psychiatry. 2003;160:105111.Google Scholar
6.Miller, KK, Biller, BM, Beauregard, C, et al. Effects of testosterone replacement in androgen-deficient women with hypopituitarism: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2006;91:16831690.CrossRefGoogle ScholarPubMed
7.Miller, KK, Grieco, KA, Klibanski, A. Testosterone administration in women with anorexia nervosa. J Clin Endocrinol Metab. 2005;90:14281433.Google Scholar
8.Shifren, JL, Braunstein, GD, Simon, JA, et al. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med. 2000;343:682688.Google Scholar
9.Dias, RS, Kerr-Correa, F, Moreno, RA, et al. Efficacy of hormone therapy with and without methyltestosterone augmentation of venlafaxine in the treatment of postmenopausal depression: a double-blind controlled pilot study. Menopause. 2006;13:202211.Google Scholar
10.First, M, Spitzer, R, Gibbon, M, Williams, J. Structured clinical interview for DSM-IV Axis I disorders -- patient edition (SCID-I/P, version 2.0). New York, NY: Biometrics Research Department, New York State Psychiatric Institute; 1995.Google Scholar
11.Sheeran, T, Zimmerman, M. Factor structure of the Psychiatric Diagnostic Screening Questionnaire (PDSQ), a screening questionnaire for DSM-IV axis I disorders. J Behav Ther Exp Psychiatry. 2004;35:4955.CrossRefGoogle ScholarPubMed
12.Montgomery, SM. Depressive symptoms in acute schizophrenia. Prog Neuropsychopharmacol. 1979;3:429433.Google Scholar
13.Guy, W. ECDEU assessment manual for psychopharmacology, revised. Rockville, MD: National Institute of Mental Health; 1976.Google Scholar
14.Moncada, E. Familial study of hirsutism. J Clin Endocrinol Metab. 1970;31:556564.Google Scholar
15.Bardin, CW, Lipsett, MB. Testosterone and androstenedione blood production rates in normal women and women with idiopathic hirsutism or polycystic ovaries. J Clin Invest. 1967;46:891902.Google Scholar
16.Kirschner, MA, Bardin, CW. Androgen production and metabolism in normal and virilized women. Metabolism. 1972;21:667688.Google Scholar
17.Longcope, C, Jaffee, W, Griffing, G. Production rates of androgens and oestrogens in post-menopausal women. Maturitas. 1981;3:215223.CrossRefGoogle ScholarPubMed
18.Miller, KK, Rosner, W, Lee, H, et al. Measurement of free testosterone in normal women and women with androgen deficiency: comparison of methods. J Clin Endocrinol Metab. 2004;89:525533.CrossRefGoogle ScholarPubMed
19.Marcus, RN, McQuade, RD, Carson, WH, et al. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a second multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol. 2008;28:156165.Google Scholar
20.Papakostas, GI, Shelton, RC, Smith, J, Fava, M. Augmentation of antidepressants with atypical antipsychotic medications for treatment-resistant major depressive disorder: a meta-analysis. J Clin Psychiatry. 2007;68:826831.Google Scholar
21.Khan, AA, Gardner, CO, Prescott, CA, Kendler, KS. Gender differences in the symptoms of major depression in opposite-sex dizygotic twin pairs. Am J Psychiatry. 2002;159:14271429.Google Scholar
22.Fava, M, Thase, ME, DeBattista, C. A multicenter, placebo-controlled study of modafinil augmentation in partial responders to selective serotonin reuptake inhibitors with persistent fatigue and sleepiness. J Clin Psychiatry. 2005;66:8593.Google Scholar
23.Fava, M, Thase, ME, DeBattista, C, Doghramji, K, Arora, S, Hughes, RJ. Modafinil augmentation of selective serotonin reuptake inhibitor therapy in MDD partial responders with persistent fatigue and sleepiness. Ann Clin Psychiatry. 2007;19:153159.CrossRefGoogle ScholarPubMed
24.Menza, MA, Kaufman, KR, Castellanos, A. Modafinil augmentation of antidepressant treatment in depression. J Clin Psychiatry. 2000;61:378381.Google Scholar
25.Thase, ME, Fava, M, DeBattista, C, Arora, S, Hughes, RJ. Modafinil augmentation of SSRI therapy in patients with major depressive disorder and excessive sleepiness and fatigue: a 12-week, open-label, extension study. CNS Spectr. 2006;11:93102.Google Scholar
26.Wang, C, Alexander, G, Berman, N, et al. Testosterone replacement therapy improves mood in hypogonadal men--a clinical research center study. J Clin Endocrinol Metab. 1996;81:35783583.Google Scholar
27.Rabkin, JG, Wagner, GJ, McElhiney, MC, Rabkin, R, Lin, SH. Testosterone versus fluoxetine for depression and fatigue in HIV/AIDS: a placebo-controlled trial. J Clin Psychopharmacol. 2004;24:379385.CrossRefGoogle ScholarPubMed
28.Rabkin, JG, Wagner, GJ, Rabkin, R. A double-blind, placebo-controlled trial of testosterone therapy for HIV-positive men with hypogonadal symptoms. Arch Gen Psychiatry. 2000;57:141147; discussion 155-146.CrossRefGoogle ScholarPubMed
29.Kennedy, SH, Dickens, SE, Eisfeld, BS, Bagby, RM. Sexual dysfunction before antidepressant therapy in major depression. J Affect Disord. 1999;56:201208.CrossRefGoogle ScholarPubMed
30.Zajecka, J, Mitchell, S, Fawcett, J. Treatment-emergent changes in sexual function with selective serotonin reuptake inhibitors as measured with the Rush Sexual Inventory. Psychopharmacol Bull. 1997;33:755760.Google ScholarPubMed
31.Fava, M, Rankin, M. Sexual functioning and SSRIs. J Clin Psychiatry. 2002;63(Suppl 5):1316; discussion 23-15.Google ScholarPubMed
32.Wang, C, Swerdloff, RS, Iranmanesh, A, et al. Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. J Clin Endocrinol Metab. 2000;85:28392853.Google Scholar
33.Shifren, JL, Davis, SR, Moreau, M, et al. Testosterone patch for the treatment of hypoactive sexual desire disorder in naturally menopausal women: results from the INTIMATE NM1 Study. Menopause. 2006;13:770779.Google Scholar
34.Braunstein, GD, Sundwall, DA, Katz, M, et al. Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial. Arch Intern Med. 2005;165:15821589.Google Scholar
35.Davis, SR, Moreau, M, Kroll, R, et al. Testosterone for low libido in postmenopausal women not taking estrogen. N Engl J Med. 2008;359:20052017.CrossRefGoogle Scholar
36.Davis, SR, van der Mooren, MJ, van Lunsen, RH, et al. Efficacy and safety of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial. Menopause. 2006;13:387396.Google Scholar
37.Buster, JE, Kingsberg, SA, Aguirre, O, et al. Testosterone patch for low sexual desire in surgically menopausal women: a randomized trial. Obstet Gynecol. 2005;105(5 Pt 1):944952.Google Scholar
38.Simon, J, Braunstein, G, Nachtigall, L, et al. Testosterone patch increases sexual activity and desire in surgically menopausal women with hypoactive sexual desire disorder. J Clin Endocrinol Metab. 2005;90:52265233.Google Scholar