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Riebel, Marco ; Brunner, Lisa-Marie ; Nothdurfter, Caroline ; Wein, Simon ; Schwarzbach, Jens V. ; Liere, Philippe ; Schumacher, Michael ; Rupprecht, Rainer

Neurosteroids and translocator protein 18 kDa (TSPO) ligands as novel treatment options in depression

Article

Riebel, Marco , Brunner, Lisa-Marie, Nothdurfter, Caroline, Wein, Simon, Schwarzbach, Jens V. , Liere, Philippe, Schumacher, Michael and Rupprecht, Rainer (2024) Neurosteroids and translocator protein 18 kDa (TSPO) ligands as novel treatment options in depression. European Archives of Psychiatry and Clinical Neuroscience, pp. 1-11.

DOI to cite this document: 10.5283/epub.58629


Abstract

Recently, the gamma-aminobutyric acid (GABA) system has come into focus for the treatment of anxiety, postpartum depression, and major depressive disorder. Endogenous 3α-reduced steroids such as allopregnanolone are potent positive allosteric modulators of GABAA receptors and have been known for decades. Current industry developments and first approvals by the U.S. food and drug administration ...

Recently, the gamma-aminobutyric acid (GABA) system has come into focus for the treatment of anxiety, postpartum depression, and major depressive disorder. Endogenous 3α-reduced steroids such as allopregnanolone are potent positive allosteric modulators of GABAA receptors and have been known for decades. Current industry developments and first approvals by the U.S. food and drug administration (FDA) for the treatment of postpartum depression with exogenous analogues of these steroids represent a major step forward in the field. 3α-reduced steroids target both synaptic and extrasynaptic GABAA receptors, unlike benzodiazepines, which bind to synaptic receptors. The first FDA-approved 3α-reduced steroid for postpartum depression is brexanolone, an intravenous formulation of allopregnanolone. It has been shown to provide rapid relief of depressive symptoms. An orally available 3α-reduced steroid is zuranolone, which also received FDA approval in 2023 for the treatment of postpartum depression. Although a number of studies have been conducted, the efficacy data were not sufficient to achieve approval of zuranolone in major depressive disorder by the FDA in 2023. The most prominent side effects of these 3α-reduced steroids are somnolence, dizziness and headache. In addition to the issue of efficacy, it should be noted that current data limit the use of these compounds to two weeks. An alternative to exogenous 3α-reduced steroids may be the use of substances that induce endogenous neurosteroidogenesis, such as the translocator protein 18 kDa (TSPO) ligand etifoxine. TSPO has been extensively studied for its role in steroidogenesis, in addition to other functions such as anti-inflammatory and neuroregenerative properties. Currently, etifoxine is the only clinically available TSPO ligand in France for the treatment of anxiety disorders. Studies are underway to evaluate its antidepressant potential. Hopefully, neurosteroid research will lead to the development of fast-acting antidepressants.



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Details

Item typeArticle
Journal or Publication TitleEuropean Archives of Psychiatry and Clinical Neuroscience
PublisherSpringer
Open Access TypeDEAL (Springer)
Page Rangepp. 1-11
Date8 July 2024
Date of publication13 Jul 2024 08:46
InstitutionsMedicine > Lehrstuhl für Psychiatrie und Psychotherapie
Identification Number
ValueType
10.1007/s00406-024-01843-7DOI
KeywordsNeurosteroids · TSPO · Depression · Treatment · GABAA receptor
Dewey Decimal Classification600 Technology > 610 Medical sciences Medicine
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgPartially
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-586298
Item ID58629

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