Etifoxine is non-inferior than clonazepam for reduction of anxiety symptoms in the treatment of anxiety disorders: a randomized, double blind, non-inferiority trial

Vicente, Benjamín; Saldivia, Sandra; Hormazabal, Naín; Bustos, Claudio; Rubi, Patricia

doi:10.1007/s00213-020-05617-6

Cited by 14 publications

(12 citation statements)

References 37 publications

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“…Initial clinical studies with etifoxine have provided the first evidence for a clinical anxiolytic effect of etifoxine, which showed comparable efficacy the benzodiazepine lorazepam patients suffering from adjustment disorders with anxiety [109]. The anxiolytic effects of etifoxine comparable to clonazepam recently been confirmed in a randomized controlled double-blind clinical trial in patients with anxiety disorder [110]. Although no clinical studies are available in depressed patients to date, TSPO ligands may also be promising agents for the treatment of depression.…”

Section: Tspo Expression Neuroimaging and Therapeutic Effects Of Tspo...mentioning

confidence: 99%

Translocator protein (18kDa) TSPO: a new diagnostic or therapeutic target for stress-related disorders?

et al. 2022

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Efficient treatment of stress-related disorders, such as depression, is still a major challenge. The onset of antidepressant drug action is generally quite slow, while the anxiolytic action of benzodiazepines is considerably faster. However, their long-term use is impaired by tolerance development, abuse liability and cognitive impairment. Benzodiazepines act as positive allosteric modulators of ɣ-aminobutyric acid type A (GABA A ) receptors. 3α-reduced neurosteroids such as allopregnanolone also are positive allosteric GABA A receptor modulators, however, through a site different from that targeted by benzodiazepines. Recently, the administration of neurosteroids such as brexanolone or zuranolone has been shown to rapidly ameliorate symptoms in post-partum depression or major depressive disorder. An attractive alternative to the administration of exogenous neurosteroids is promoting endogenous neurosteroidogenesis via the translocator protein 18k Da (TSPO). TSPO is a transmembrane protein located primarily in mitochondria, which mediates numerous biological functions, e.g., steroidogenesis and mitochondrial bioenergetics. TSPO ligands have been used in positron emission tomography (PET) studies as putative markers of microglia activation and neuroinflammation in stress-related disorders. Moreover, TSPO ligands have been shown to modulate neuroplasticity and to elicit antidepressant and anxiolytic therapeutic effects in animals and humans. As such, TSPO may open new avenues for understanding the pathophysiology of stress-related disorders and for the development of novel treatment options.

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Section: Tspo Expression Neuroimaging and Therapeutic Effects Of Tspo...mentioning

confidence: 99%

Translocator protein (18kDa) TSPO: a new diagnostic or therapeutic target for stress-related disorders?

et al. 2022

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“…Given the close association of the C5a/C5aR signaling with chronic pain and depression, the prospects of targeted drug treatments for chronic pain and depression are also promising. Additionally, clinical studies have shown that C1q and translocator protein (TSPO) are elevated in depression, TSPO ligand drugs can exert anti-anxiety and anti-depressive effects by promoting endogenous neurosteroid synthesis [ 85 ]. Recent studies have shown that TSPO ligands can cause neuronal atrophy and loss by marking C1q, and treatment with TSPO ligands can reduce the levels of C1q in microglial cells [ 86 ].…”

Section: Discussionmentioning

confidence: 99%

The complement system: a potential target for the comorbidity of chronic pain and depression

Tang,

Hu,

Zou

et al. 2024

Korean J Pain

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The mechanisms of the chronic pain and depression comorbidity have gained significant attention in recent years. The complement system, widely involved in central nervous system diseases and mediating non-specific immune mechanisms in the body, remains incompletely understood in its involvement in the comorbidity mechanisms of chronic pain and depression. This review aims to consolidate the findings from recent studies on the complement system in chronic pain and depression, proposing that it may serve as a promising shared therapeutic target for both conditions. Complement proteins C1q, C3, C5, as well as their cleavage products C3a and C5a, along with the associated receptors C3aR, CR3, and C5aR, are believed to have significant implications in the comorbid mechanism. The primary potential mechanisms encompass the involvement of the complement cascade C1q/C3-CR3 in the activation of microglia and synaptic pruning in the amygdala and hippocampus, the role of complement cascade C3/C3a-C3aR in the interaction between astrocytes and microglia, leading to synaptic pruning, and the C3a-C3aR axis and C5a-C5aR axis to trigger inflammation within the central nervous system. We focus on studies on the role of the complement system in the comorbid mechanisms of chronic pain and depression.

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“…Recently a randomized, double-blind clinical trial showed that etifoxine (a TSPO ligand) is effective for reduction of anxiety symptoms in patients with anxiety disorder. 348 To date, no clinal study that treats chronic pain with TSPO ligand is available.…”

Section: A New Strategy For Treatment Of Chronic Painmentioning

confidence: 99%

Normalization of Neuroinflammation: A New Strategy for Treatment of Persistent Pain and Memory/Emotional Deficits in Chronic Pain

Liu¹

2022

JIR

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Chronic pain, which affects around 1/3 of the world population and is often comorbid with memory deficit and mood depression, is a leading source of suffering and disability. Studies in past decades have shown that hyperexcitability of primary sensory neurons resulting from abnormal expression of ion channels and central sensitization mediated pathological synaptic plasticity, such as long-term potentiation in spinal dorsal horn, underlie the persistent pain. The memory/emotional deficits are associated with impaired synaptic connectivity in hippocampus. Dysregulation of numerous endogenous proteins including receptors and intracellular signaling molecules is involved in the pathological processes. However, increasing knowledge contributes little to clinical treatment. Emerging evidence has demonstrated that the neuroinflammation, characterized by overproduction of pro-inflammatory cytokines and glial activation, is reliably detected in humans and animals with chronic pain, and is sufficient to induce persistent pain and memory/emotional deficits. The abnormal expression of ion channels and pathological synaptic plasticity in spinal dorsal horn and in hippocampus are resulting from neuroinflammation. The neuroinflammation is initiated and maintained by the interactions of circulating monocytes, glial cells and neurons. Obviously, unlike infectious diseases and cancer, which are caused by pathogens or malignant cells, chronic pain is resulting from alterations of cells and molecules which have numerous physiological functions. Therefore, normalization (counterbalance) but not simple inhibition of the neuroinflammation is the right strategy for treating neuronal disorders. Currently, no such agent is available in clinic. While experimental studies have demonstrated that intracellular Mg 2+ deficiency is a common feature of chronic pain in animal models and supplement Mg 2+ are capable of normalizing the neuroinflammation, activation of upregulated proteins that promote recovery, such as translocator protein (18k Da) or liver X receptors, has a similar effect. In this article, relevant experimental and clinical evidence is reviewed and discussed.

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Etifoxine is non-inferior than clonazepam for reduction of anxiety symptoms in the treatment of anxiety disorders: a randomized, double blind, non-inferiority trial

Cited by 14 publications

References 37 publications

Translocator protein (18kDa) TSPO: a new diagnostic or therapeutic target for stress-related disorders?

Translocator protein (18kDa) TSPO: a new diagnostic or therapeutic target for stress-related disorders?

The complement system: a potential target for the comorbidity of chronic pain and depression

Normalization of Neuroinflammation: A New Strategy for Treatment of Persistent Pain and Memory/Emotional Deficits in Chronic Pain

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