<p>An update on the anxiolytic and neuroprotective properties of etifoxine: from brain GABA modulation to a whole-body mode of action</p>

Abstract

Treating the signs and symptoms of anxiety is an everyday challenge in clinical practice. When choosing between treatment options, anxiety needs to be understood in the situational, psychiatric, and biological context in which it arises. Etifoxine, a non-benzodiazepine anxiolytic drug belonging to the benzoxazine class, is an effective treatment for anxiety in response to a stressful situation. In the present review, we focused on several aspects of the cerebral and somatic biological mechanisms involved in anxiety and investigated the extent to which etifoxine’s mode of action can explain its anxiolytic activity. Its two mechanisms of action are the modulation of GABAergic neurotransmission and neurosteroid synthesis. Recent data suggest that the molecule possesses neuroprotective, neuroplastic, and anti-inflammatory properties. Etifoxine was first shown to be an effective anxiolytic in patients in clinical studies comparing it with clobazam, sulpiride, and placebo. Randomized controlled studies have demonstrated its anxiolytic efficacy in patients with adjustment disorders (ADs) with anxiety, showing it to be superior to buspirone and comparable to lorazepam and phenazepam, with a greater number of markedly improved responders and a better therapeutic index. Etifoxine’s noninferiority to alprazolam has also been demonstrated in a comparative trial. Significantly less rebound anxiety was observed after abrupt cessation of etifoxine compared with lorazepam or alprazolam. Consistent with this finding, etifoxine appears to have a very low dependence potential. Unlike lorazepam, it has no effect on psychomotor performance, vigilance, or free recall. Severe adverse events are in general rare. Skin and subcutaneous disorders are the most frequently reported, but these generally resolve after drug cessation. Taken together, its dual mechanisms of action in anxiety and the positive data yielded by clinical trials support the use of etifoxine for treating the anxiety signs and symptoms of individuals with ADs.

Presentation and management of anxiety in individuals with acute symptomatic or asymptomatic COVID-19 infection, and in the post-COVID-19 recovery phase

“…Long-term use of benzodiazepines for treatment of anxiety may cause anxiety after discontinuation (rebound), indirectly, by impairing sleep, and may cause delirium (Chouinard 2004). Therefore, in such instances, non-benzodiazepine anxiolytics should be substituted as a treatment (Nuss et al 2019). In addition, corticosteroid treatments are reported to correlate with anxiety in COVID-19 patients , which is expected due to the effects of corticosteroids on the hypothalamic-pituitaryadrenal (HPA) axis.…”

Analysis of the Underlying Mechanism of the Jiu Wei Zhen Xin Formula for Treating Generalized Anxiety Disorder Based on Network Pharmacology of Traditional Chinese Medicine

“…Brain circuits in the amygdala are thought to contain an inhibitory network of gamma-aminobutyric acid (GABAergic) interneurons, and thus this neurotransmitter plays a key role in regulating anxiety responses in both normal and pathological states [ 16 ]. Reducing GABA-mediated inhibition is one of the effective methods available for the modulation of neuronal excitability [ 17 ]. Many researchers have expressed great interest in developing novel medications acting on different subtypes of GABA receptors to manage GAD [ 18 , 19 ] ( Figure 8 ).…”

Post-traumatic stress disorder – from traumatic neurosis to ICD-11: features of diagnosis and selection of therapy

“…Кроме того, этифоксин не взаимодействует с кортикотропин-рилизинг-факторами, тем самым минимально вмешиваясь в метаболизм глюкокортикоидов. У этифоксина нет избыточной седации и влияния на память, свой ственных бензодиазепинам, при этом в сравнительных исследованиях с ними он продемонстрировал свою высокую эффективность [77][78][79][80][81][82][83][84][85][86][87][88][89].…”