Etifoxine, sold under the trade name Stresam among others, is a nonbenzodiazepine anxiolytic agent, primarily indicated for short-term management of adjustment disorder, specifically instances of situational depression accompanied by anxiety, such as stress-induced anxiety.
associated with etifoxine use include slight drowsiness, headache, , and drug allergy.
Etifoxine was developed in the 1960s and was introduced for medical use in France in 1979.
Medical uses
Etifoxine has historically been used in the treatment of "
psychosomatic manifestations of
anxiety", for instance "autonomic
dystonia, particularly with
cardiovascular expression".
Subsequently, the indication for etifoxine has been more formalized as treatment of adjustment disorder (situational depression) with anxiety (ADWA) (e.g., stress-related anxiety).
Etifoxine has been found to reduce scores on the Hamilton Anxiety Rating Scale (HAM-A) in people with adjustment disorder with anxiety by approximately 50 to 75% after 4weeks of treatment in
(e.g., AMETIS, ETILOR, ETIZAL, STRETI studies).
The medication is similarly effective or more effective than
like
lorazepam,
alprazolam, and
clonazepam and more effective than
buspirone for adjustment disorder with anxiety on the basis of directly comparative randomized controlled trials.
However, in the AMETIS study, both etifoxine and lorazepam failed to show greater effectiveness over
placebo.
In the trials comparing etifoxine to clonazepam, lorazepam, and alprazolam, total daily doses of the benzodiazepines were limited to their maintenance dose, set at 1 mg, 2 mg, and 1.5 mg, respectively, in t.i.d. Such an inflexible dosing regime limits the utility benzodiazepines offer in practice; e.g. lorazepam and alprazolam can be used as needed for situational anxiety in which continuous use is unnecessary or excessive, while clonazepam can be titrated to response when continuous relief is indicated, up to a maximum of 4 mg a day, four times greater than the dose used in comparison with etifoxine over the 24 week duration of the trial. In general, they offer a degree of personalization that is not possible with etifoxine. Indeed, better evidence is required before etifoxine can be said to replace benzodiazepines in practice, especially considering the trials above were relatively small in size, along with the high attrition rates and lack of personalization of the benzodiazepines used.
The usual dosage of etifoxine (as the hydrochloride salt) is 150 to 200mg per day in divided doses of 50 to 100mg two to three times per day (e.g., 50mg–50mg–100mg).
Available forms
Etifoxine is provided in the form of oral capsules containing 50mg etifoxine hydrochloride.
Contraindications
Etifoxine is
contraindication in people with circulatory shock, severe
liver impairment, severe kidney impairment, myasthenia gravis,
galactosemia (due to
lactose in the
drug formulation), severe respiratory failure, and hypersensitivity (allergy) to etifoxine.
The medication is not recommended in children or adolescents under the age of 18
and is not recommended during
pregnancy and
breastfeeding due to insufficient data.
Caution is warranted with regard to combining etifoxine and other central depressants such as
, central
,
,
sedative , and alcohol.
Side effects
of etifoxine include slight
drowsiness and
headache.
Rarely, etifoxine can cause benign
or
skin rash and
drug allergy such as
urticaria and
angioedema.
Etifoxine shows less adverse effects of anterograde amnesia,
sedation, impaired psychomotor performance, and withdrawal syndromes than those of
.
[ No cases of drug abuse or drug dependence with etifoxine were identified in a French pharmacovigilance survey, which is also in contrast to benzodiazepines.]
Etifoxine has been associated rarely with cases of severe dermal toxicity and liver toxicity.
Pharmacology
Pharmacodynamics
Unlike benzodiazepines, etifoxine may produce its anxiolytic effects through a dual mechanism, by directly binding to GABAA receptor and (purportedly, exact binding site undetermined) to the mitochondrial translocator protein (TSPO). This results in stimulation of the biosynthesis of endogenous , for instance allopregnanolone, a highly potent GABAA receptor positive allosteric modulator.
At GABAA receptors etifoxine binds at the α+β− interface and preferentially potentiates α2β3γ2 and α3β3γ2 receptor types.
Pharmacokinetics
Etifoxine is taken via oral administration.
Chemistry
Etifoxine is a nonbenzodiazepine—that is, it is similarly a GABAA receptor positive allosteric modulator but its chemical structure is distinct from that of .
Etifoxine is used pharmaceutically as the hydrochloride salt.
( S)-Etifoxine, the ( S) enantiomer of etifoxine, was under development by Anvyl Pharmaceuticals for the treatment of neuropathic pain, but development was discontinued.
History
Etifoxine was developed by Hoechst AG in the 1960s.
Society and culture
Names
Etifoxine is the generic term of the drug and its , , and .
Availability
Etifoxine has been marketed in 53countries as of 2022.
See also
Further reading
External links
target="_blank" rel="nofollow"> Stesam (etifoxine hydrochloride) Summary of Product Characteristics (SPC)
