TY - JOUR
T1 - Low-dose testosterone augmentation for antidepressant-resistant major depressive disorder in women
T2 - An 8-week randomized placebo-controlled study
AU - Dichtel, Laura E.
AU - Carpenter, Linda L.
AU - Nyer, Maren
AU - Mischoulon, David
AU - Kimball, Allison
AU - Deckersbach, Thilo
AU - Dougherty, Darin D.
AU - Schoenfeld, David A.
AU - Fisher, Lauren
AU - Cusin, Cristina
AU - Dording, Christina
AU - Trinh, Nhi Ha
AU - Pedrelli, Paola
AU - Yeung, Albert
AU - Farabaugh, Amy
AU - Papakostas, George I.
AU - Chang, Trina
AU - Shapero, Benjamin G.
AU - Chen, Justin
AU - Cassano, Paolo
AU - Hahn, Emily M.
AU - Rao, Elizabeth M.
AU - Brady, Roscoe O.
AU - Singh, Ravinder J.
AU - Tyrka, Audrey R.
AU - Price, Lawrence H.
AU - Fava, Maurizio
AU - Miller, Karen K.
N1 - Funding Information:
Supported by NIMH grant R34 MH099315 (Drs. Miller, Fava, and Carpenter). Additionally, individual investigators were supported by NIH grants K24HL092902 (Dr. Miller), K23 DK113220 (Dr. Dichtel), K23 MH100623 (Dr. Brady), K23HD087464 (Dr. Fisher), K23AT008043 (Dr. Nyer), K23 DK097356-02 (Dr. Chang), and T32 DK007028 (Dr. Kimball); the Dupont-Warren Fellowship and Livingston Award through the Harvard Department of Psychiatry (Dr. Cassano); and the National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award from the Brain and Behavior Research Foundation (Dr. Cassano). Lawley Pharmaceuticals provided study medication and identical placebo at no cost. The Foundation for Women’s Wellness provided funding for the fMRI substudy (Drs. Dichtel and Miller).
Funding Information:
Supported by NIMH grant R34 MH099315 (Drs. Miller, Fava, and Carpenter). Additionally, individual investigators were supported by NIH grants K24HL092902 (Dr. Miller), K23 DK113220 (Dr. Dichtel), K23 MH100623 (Dr. Brady), K23HD087464 (Dr. Fisher), K23AT008043 (Dr. Nyer), K23 DK097356-02 (Dr. Chang), and T32 DK007028 (Dr. Kimball); the Dupont-Warren Fellowship and Livingston Award through the Harvard Department of Psychiatry (Dr. Cassano); and the National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award from the Brain and Behavior Research Foundation (Dr. Cassano). Lawley Pharmaceuticals provided study medication and identical placebo at no cost. The Foundation for Women's Wellness provided funding for the fMRI substudy (Drs. Dichtel and Miller).
Publisher Copyright:
© 2020 American Psychiatric Association. All rights reserved.
PY - 2020/10
Y1 - 2020/10
N2 - 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.
AB - 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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U2 - 10.1176/appi.ajp.2020.19080844
DO - 10.1176/appi.ajp.2020.19080844
M3 - Article
C2 - 32660299
AN - SCOPUS:85092314386
SN - 0002-953X
VL - 177
SP - 965
EP - 973
JO - American Journal of Psychiatry
JF - American Journal of Psychiatry
IS - 10
ER -