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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

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

Veröffentlichungsdatum dieses Volltextes: 13 Jul 2024 08:46
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.58629


Zusammenfassung

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

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftEuropean Archives of Psychiatry and Clinical Neuroscience
Verlag:Springer
Seitenbereich:S. 1-11
Datum8 Juli 2024
InstitutionenMedizin > Lehrstuhl für Psychiatrie und Psychotherapie
Identifikationsnummer
WertTyp
10.1007/s00406-024-01843-7DOI
Stichwörter / KeywordsNeurosteroids · TSPO · Depression · Treatment · GABAA receptor
Dewey-Dezimal-Klassifikation600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin
StatusVeröffentlicht
BegutachtetJa, diese Version wurde begutachtet
An der Universität Regensburg entstandenZum Teil
URN der UB Regensburgurn:nbn:de:bvb:355-epub-586298
Dokumenten-ID58629

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