etifoxine and Anxiety-Disorders

Anxiety and adjustment disorders are among the most prevalent mental health conditions. This review focuses on γ-aminobutyric acid receptor type A (GABA. We used available data from the recent literature to update the mode of action of anxiolytics. We focussed our search on anxiolytics acting at GABA. Considering the adverse effects of current treatments aimed at increasing inhibitory controls, optimisation of existing pharmacotherapies is of crucial importance. Among the alternative compounds targeting the GABAergic system, translocator protein (TSPO) ligands, such as etifoxine (EFX), which promote endogenous neurosteroidogenesis, are emerging as promising candidates for anxiety relief. In several papers comparing the efficacy of benzodiazepines and EFX, EFX showed interesting properties with limited side effects. Indeed, neurosteroids are potent GABA. Novel therapeutic strategies have been emerging following the recognition of neurosteroids as potent anxiolytics. Featured at the top of the list for well-tolerated anxiety relief, TSPO ligands such as etifoxine appear promising.

Topics: Adjustment Disorders; Anti-Anxiety Agents; Anxiety Disorders; Humans; Oxazines; Receptors, GABA-A

It is known, that anxiety is one of the most wide-spread mental disorders in-between psychiatric state and it takes part in pathogenesis a lot of somatic diseases as well. At the same time the host bowel microbiota participates in metabolic control of vital human functions such as mood and behavioural reactions. This title connection reveals some new therapeutic opportunity in treatment of psychiatric disorders that based on using with probiotics. In case non-clinically significant anxiety it is claimed to use probiotic (Enterol) however in case clinically significant anxiety it is claimed to use non-benzodiazepine tranquilizer (Stresam).

Topics: Anti-Anxiety Agents; Anxiety Disorders; Behavior; Humans; Intestinal Diseases; Oxazines; Probiotics

Topics: Adrenal Cortex Hormones; Amygdala; Anti-Anxiety Agents; Anxiety Disorders; Brain; Cerebrovascular Circulation; Cognition Disorders; Dementia; Humans; Magnetic Resonance Imaging; Oxazines; Receptors, GABA-A; Risk Factors

To determine whether etifoxine, a non-benzodiazepine drug of the benzoxazine family, is non-inferior compared with clonazepam in the treatment of anxiety disorders.. A randomized controlled double blind trial with parallel groups was conducted. A total of 179 volunteer patients with a diagnosis of anxiety disorder (DSM-IV), between 18 and 64 years of age, participated in this study. The experimental group received 150 mg/day of etifoxine and the control 1 mg/day of clonazepam, both in three daily doses for 12 weeks. This treatment was completed by 87 participants, and 70 were available for follow-up at 24 weeks from start of treatment. The primary objective was a non-inferiority comparison between etifoxine and clonazepam in the decrease of anxiety symptoms (HAM-A) at 12 weeks of treatment. Secondary outcomes included the evaluation of medication side effects (UKU), anxiety symptoms at 24 weeks of treatment, and clinical improvement (CGI). Data analysis included multiple imputation of missing data. The effect of etifoxine on the HAM-A, UKU, and CGI was evaluated with the intention of treatment, and a sensitivity analysis of the results was conducted. Non-inferiority would be declared by a standardized mean difference (SMD) between clonazepam and etifoxine not superior to 0.31 in favour of clonazepam.. Using imputed data, etifoxine shows non-inferiority to clonazepam on the reduction of anxiety symptoms at the 12-week (SMD = 0.407; 95% CI, 0.069, 0.746) and 24-week follow-ups (SMD = 0.484; 95% CI, 0.163, 0.806) and presented fewer side effects (SMD = 0.58; 95% CI, 0.287, 0.889). LOCF analysis shows that etifoxine is non-inferior to clonazepam on reduction of anxiety symptoms and adverse symptoms even when no change was assigned as result to participant whom withdrew. Non-inferiority could be declared for clinical improvement (SMD = 0.326; 95% CI, - 0.20, 0.858).. Etifoxine was non-inferior to clonazepam on reduction of anxiety symptoms, adverse effects, and clinical improvement.

Topics: Adolescent; Adult; Aged; Anti-Anxiety Agents; Anxiety Disorders; Clonazepam; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Oxazines; Treatment Outcome; Young Adult

Topics: Adverse Drug Reaction Reporting Systems; Anti-Anxiety Agents; Anxiety Disorders; France; Humans; Oxazines

Dysfunction of GABAergic transmission related to abnormal expression of GABA(A) receptor subunits in specific brain regions underlies some pathological anxiety states. Besides involvement of the benzodiazepine recognition site of GABA(A) receptor in the expression of anxiety-like behaviour, the roles of the β(2)/β(3) subunits are not well characterized. To address this issue, the experimental design of this study utilized the GABAergic compound etifoxine (with a preferential effectiveness after binding to a specific site at β(2)/β(3) subunits) tested in two inbred mouse strains: BALB/cByJ and C57BL/6J mice using three behavioural paradigms (light/dark box, elevated plus maze and restraint stress-induced small intestinal transit inhibition) and the t-butylbicyclophosphorothionate-induced convulsions model. Etifoxine plasma and brain levels and β(2)/β(3) mRNAs and protein expression levels in various brain regions were compared between the two strains. The two mouse strains differed markedly in basal anxiety level. Etifoxine exhibited more pronounced anxiolytic and anticonvulsant effects in the BALB/cByJ mice compared to the C57BL/6J mice. The etifoxine brain/plasma ratios of the two strains were not different. Beta2 subunit mRNA and protein expression levels were around 25 and 10% higher respectively in the anterodorsal nucleus of the thalamus and the CA3 field of hippocampus of BALB/cByJ mice compared to C57BL/6J mice. Beta3 subunit mRNA and protein expression levels did not differ between the two strains. Based on these results, it is suggested that overexpression of GABA(A) receptor β(2) subunit in BALB/cByJ mice relative to C57BL/6j mice contributes to the dysfunction in GABA(A) transmission in regions of brain known to regulate responses to stress. The dysregulated GABA(A) function in BALB/cByJ mice may be corrected by the administration of etifoxine.

Topics: Animals; Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Behavior, Animal; Brain; Hippocampus; Intestine, Small; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Motor Activity; Oxazines; Receptors, GABA-A; Seizures