The Translocator Protein 18kDa Ligand Etifoxine in the Treatment of Depressive Disorders-a Double-blind, Randomized, Placebo-controlled Proof-of-concept Study

Overview

Journal Trials

Publisher Biomed Central

Specialties General Medicine
Pharmacology

Date 2024 Apr 22

PMID 38650030

Authors

Lisa-Marie Brunner

Marco Riebel

Simon Wein

Michael Koller

Florian Zeman

Gunnar Huppertz

Tanja Emmer

Yvonne Eberhardt

Jens Schwarzbach

Rainer Rupprecht

Caroline Nothdurfter

Affiliations

Soon will be listed here.

Abstract

Background: Recent developments suggest that neurosteroids may achieve rapid antidepressant effects. As such, neurosteroidogenesis mediated by the translocator protein 18 kDa (TSPO) might constitute a promising option for the treatment of depression. Therefore, the current clinical trial aims to get the first evidence of whether TPSO ligands promote rapid antidepressant effects. Furthermore, we study which mechanisms of action, e.g., modulation of distinct neuronal networks, neurosteroidogenesis, endocrinological mechanisms, TSPO expression or microbiome composition, contribute to their putative antidepressant effects.

Methods: This is a randomized, placebo-controlled, double-blind single-center trial of 2-week treatment with the TSPO ligand etifoxine versus placebo in depressive patients. Main eligibility criteria: male or female individuals aged 18 to 65 years with unipolar/bipolar depressive disorder with no other psychiatric main diagnosis or acute neurological/somatic disorder or drug/alcohol dependence during their lifetime. The primary endpoint is the time point at which 50% of the maximal effect has occurred (ET50) estimated by the scores of the Hamilton Depression Scale (HAMD-21). A total of 20 patients per group are needed to detect changes of therapeutic efficacy about 5% and changes of ET50 about 10% with a power of 70%. Assuming a drop-out rate of 10-20%, 50 patients will be randomized in total. The study will be conducted at the Department of Psychiatry and Psychotherapy of the University of Regensburg.

Discussion: This study will provide a first proof-of-concept on the potential of the TSPO ligand etifoxine in the treatment of depressive disorders.

Trial Registration: Clinical Trials Register (EudraCT number: 2021-006773-38 , registration date: 14 September 2022) and German Register of Clinical Studies (DRKS number: DRKS00031099 , registration date: 23 January 2023).

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PMID: 39405127 PMC: 11717590. DOI: 10.1097/QAD.0000000000004034.

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

Riebel M, Brunner L, Nothdurfter C, Wein S, Schwarzbach J, Liere P Eur Arch Psychiatry Clin Neurosci. 2024; .

PMID: 38976049 DOI: 10.1007/s00406-024-01843-7.

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