Hormonal Treatments for Major Depressive Disorder: State of the Art
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VIEW CORRECTIONPublication: American Journal of Psychiatry
Abstract
Major depressive disorder is a common psychiatric disorder associated with marked suffering, morbidity, mortality, and cost. The World Health Organization projects that by 2030, major depression will be the leading cause of disease burden worldwide. While numerous treatments for major depression exist, many patients do not respond adequately to traditional antidepressants. Thus, more effective treatments for major depression are needed, and targeting certain hormonal systems is a conceptually based approach that has shown promise in the treatment of this disorder. A number of hormones and hormone-manipulating compounds have been evaluated as monotherapies or adjunctive treatments for major depression, with therapeutic actions attributable not only to the modulation of endocrine systems in the periphery but also to the CNS effects of hormones on non-endocrine brain circuitry. The authors describe the physiology of the hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary thyroid (HPT), and hypothalamic-pituitary-gonadal (HPG) axes and review the evidence for selected hormone-based interventions for the treatment of depression in order to provide an update on the state of this field for clinicians and researchers. The review focuses on the HPA axis–based interventions of corticotropin-releasing factor antagonists and the glucocorticoid receptor antagonist mifepristone, the HPT axis–based treatments of thyroid hormones (T3 and T4), and the HPG axis–based treatments of estrogen replacement therapy, the progesterone derivative allopregnanolone, and testosterone. While some treatments have largely failed to translate from preclinical studies, others have shown promising initial results and represent active fields of study in the search for novel effective treatments for major depression.
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Received: 19 August 2019
Revision received: 22 January 2020
Accepted: 24 February 2020
Published online: 27 May 2020
Published in print: August 01, 2020
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Competing Interests
Dr. Dwyer has received research support from the Klingenstein Third Generation Foundation and has served as a consultant for Axsome Therapeutics. Dr. Radhakrishnan has received research funding from Neurocrine Biosciences. Dr. Widge has served as a consultant for Medtronic and Circuit Therapeutics, has received speaking fees from Medtronic and Livanova, and has received research device donations from Medtronic; he has multiple patent applications in the areas of brain stimulation and biomarkers of cognitive dysfunction. Dr. Carpenter has served as a consultant for Affect Neuro, Janssen, Neurolief, Neuronetics, Nexstim, and Sage Therapeutics and has received research support from Affect Neuro, Janssen, NeoSync, Neuronetics, and Nexstim. Dr. Nemeroff has received grants or research support from NIH; he has served as a consultant for Acadia Pharmaceuticals, EMA Wellness, Gerson Lehrman Group, Intra-Cellular Therapies, Janssen Research and Development, Magstim, Navitor Pharmaceuticals, Signant Health, Sunovion Pharmaceuticals, Taisho Pharmaceutical, Takeda, TC MSO, and Xhale; he has served on scientific advisory boards of the American Foundation for Suicide Prevention, the Anxiety Disorders Association of America (ADAA), the Brain and Behavior Research Foundation, the Laureate Institute for Brain Research, Signant Health, Skyland Trail, and Xhale and on boards of directors for ADAA, Gratitude America, Smart, Inc., and Xhale; he is a stockholder in AbbVie, Antares, BI Gen Holdings, Celgene, Corcept Therapeutics, EMA Wellness, OPKO Health, Seattle Genetics, TC MSO, Trends in Pharma Development, and Xhale; he has income sources or equity of $10,000 or more from American Psychiatric Publishing, CME Outfitters, EMA Wellness, Intra-Cellular Therapies, Magstim, Signant Health, and Xhale; he holds patents on a method and devices for transdermal delivery of lithium (US 6,375,990B1), a method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay (US 7,148,027B2), and compounds, compositions, methods of synthesis, and methods of treatment (CRF Receptor Binding Ligand) (US 8,551,996B2). Dr. McDonald has received research support from Cervel Neurotherapeutics, the National Institute of Neurological Disease and Stroke, the National Institute on Aging, NeoSync, Neuronetics, NIMH, Soterix, and the Stanley Foundation; he has served as a consultant for Signant Health; he receives royalties from Oxford University Press; and he receives funding from the J.B. Fuqua Foundation. Dr. Kalin is Editor-in-Chief and Dr. Rodriguez is Deputy Editor for the American Journal of Psychiatry; the editors’ disclosures appear in the April issue of the Journal. Dr. Aftab reports no financial relationships with commercial interests.
Funding Information
National Institute of Neurological Disorders and Strokehttp://dx.doi.org/10.13039/100000065: UH3 NS100548
National Institute of Mental Healthhttp://dx.doi.org/10.13039/100000025: R01 MH119384, R21 MH113101, T32 MH018268
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