Abstract
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.
Original language | English (US) |
---|---|
Pages (from-to) | 965-973 |
Number of pages | 9 |
Journal | American Journal of Psychiatry |
Volume | 177 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2020 |
ASJC Scopus subject areas
- Psychiatry and Mental health
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Low-dose testosterone augmentation for antidepressant-resistant major depressive disorder in women : An 8-week randomized placebo-controlled study. / Dichtel, Laura E.; Carpenter, Linda L.; Nyer, Maren et al.
In: American Journal of Psychiatry, Vol. 177, No. 10, 10.2020, p. 965-973.Research output: Contribution to journal › Article › peer-review
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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). Funding Information: Dr. Dougherty has received research support and honoraria from Med-tronic. Dr. Cusin has received research support from Janssen, Otsuka, and Shenox, has participated on advisory boards or as consultant or speaker for Alkermes, Boehringer, Janssen, Lundbeck, and Takeda. Dr. Papakostas has served as a consultant for Abbott Laboratories, Alkermes, AstraZeneca, Avanir Pharmaceuticals, Brainsway, Bristol-Myers Squibb, Cephalon, Dey Pharma, Eli Lilly, GlaxoSmithKline, Evotec AG, H. Lundbeck A/S, Inflabloc Pharmaceuticals, Novartis Pharma, Otsuka Pharmaceuticals, Pamlab, Pfizer, Pierre Fabre Laboratories, Ridge Diagnostics, Shire Pharmaceuticals, Sunovion Pharmaceuticals, Takeda Pharmaceutical Company, Theracos, and Wyeth; on behalf of Massachusetts General Hospital, he has served as a consultant for Acadia Pharmaceuticals, Alphasigma USA, Axsome Therapeutics, Boston Pharmaceuticals, Cala Health, Genentech, Genomind, Janssen Global Services, Jazz Pharmaceuticals, Johnson & Johnson, Methylation Sciences, Mylan, One Carbon Therapeutics, Osmotica Pharmaceutical, Sage Therapeutics, and Taisho Pharmaceutical; he has received honoraria (for lectures or consultancy) from Abbott Laboratories, Acadia Pharmaceuticals, Alkermes, Alphasigma USA, Aso-farma Centroamerica y Caribe, Astra Zeneca, Avanir Pharmaceuticals, Bristol-Myers Squibb, Brainsway, Cephalon, Dey Pharma, Eli Lilly, Evotec AG, Forest Pharmaceuticals, GlaxoSmithKline, Inflabloc Pharmaceuticals, Grunbiotics, Hypera, Jazz Pharmaceuticals, H. Lundbeck A/S, Medichem Pharmaceuticals, Meiji Seika Pharma, Novartis Pharma, Otsuka Pharmaceuticals, Pamlab, Pfizer, Pharma Trade SAS, Pierre Fabre Laboratories, Ridge Diagnostics, Shire Pharmaceuticals, Sunovion Pharmaceuticals, Takeda Pharmaceutical Company, Theracos, Titan Pharmaceuticals, and Wyeth; he has received research support (paid to hospital) from Astra-Zeneca, Bristol-Myers Squibb, Forest Pharmaceuticals, Neuralstem, NIMH, Pamlab, Pfizer, Ridge Diagnostics, Sunovion Pharmaceuticals, Tal Medical, and Theracos; and he has served on the speakers bureau for Bristol-Myers Squibb and Pfizer. Dr. Cassano has received an unrestricted grant from Photothera Incorporated, drug donation from Teva, travel reimbursement from Pharmacia-Upjohn, consultation fees from Janssen Research and Development, and device donation from PhotoMedex; he has filed several patents related to the use of near-infrared light in psychiatry, received unrestricted funding from LiteCure, received funding from Cerebral Sciences, and co-founded and consults for Niraxx Light Therapeutics. Dr. Price has received grants or research support from NIH; he has served as a consultant for Springer, University of Texas at Austin, and Wiley; he has served on data safety and monitoring boards for Baylor University, Cleveland Clinic, Clexio Biosciences, and Worldwide Clinical Trials; and he receives royalties for OCDScales. Dr. Fava has received research support from, has served as an adviser or consultant to, has had speaking or publishing roles for, and/or has equity in Abbott, Acadia, Adamed, Advanced Meeting Partners, Affectis, Alkermes, Amarin, American Cyanamid, the American Society of Clinical Psychopharmacology, APA, Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Avanir, Axsome, Bayer, Belvoir Media Group, Best Practice Project Management, Biogen, Biohaven, BioMarin, BioResearch, Biovail, BioXcel Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, the Brain and Behavior Research Foundation, BrainCells, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Cerecor, Clarus Funds, Clexio Biosciences, Clintara, the CME Institute, CNS Response, Compellis, Covance, Covidien, Cypress, DiagnoSearch Life Sciences, Dov, Edgemont, Eisai, Eli Lilly, EnVivo, ePharmaSolutions, Epix, Euthymics Bioscience, Fabre-Kramer, Forest, Forum, Ganeden, Genomind, GlaxoSmithKline, Grünen-thal, the Harvard Clinical Research Institute, Hoffmann–La Roche, ICON, Imedex, Indivior, Ingenix, Intracellular, Janssen, Jazz, the Jed Foundation, Johnson & Johnson, Knoll, Labopharm, Lichtwer, Lorex, Lundbeck, Marinus, the Massachusetts General Hospital Psychiatry Academy, MedAvante, Merck, MSI Methylation Sciences, NARSAD, the National Center for Complementary and Alternative Medicine, the National Co-ordinating Center for Integrative Medicine, Naurex, Navitor, Nestle Health Sciences, Neuralstem, Neuronetics, NeuroRx, NextWave, NIDA, NIMH, Novartis, Nutrition 21, Orexigen, Organon, Osmotica, Otsuka, Pamlab, Pfizer, Pharmacia-Upjohn, Pharmaceutical Research Associates, Phar-mastar, Pharmavite, PharmoRx Therapeutics, Pharmaceutical Product Development, Photothera, Polaris, Praxis Precision Medicines, Precision Human Biolaboratory, Prexa, PsychoGenics, PsyBrain, Psylin, PThera, Purdue, Puretech Ventures, RCT Logic, Reckitt Benckiser, Relmada, Rexahn, Ridge Diagnostics, Roche, Sanofi-Aventis, Schering-Plough, 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.
UR - http://www.scopus.com/inward/record.url?scp=85092314386&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85092314386&partnerID=8YFLogxK
U2 - 10.1176/appi.ajp.2020.19080844
DO - 10.1176/appi.ajp.2020.19080844
M3 - Article
C2 - 32660299
AN - SCOPUS:85092314386
VL - 177
SP - 965
EP - 973
JO - American Journal of Psychiatry
JF - American Journal of Psychiatry
SN - 0002-953X
IS - 10
ER -