Long term use may result in blepharospasms. Doses of 4 mg or more may cause anterograde amnesia. In rare cases, erythema annulare centrifugumskin lesions have resulted.
Tolerance, dependence and withdrawal
Abrupt or rapid discontinuation from etizolam, as with benzodiazepines, may result in the appearance of the benzodiazepine withdrawal syndrome, including rebound insomnia. Neuroleptic malignant syndrome, a rare event in benzodiazepine withdrawal, has been documented in a case of abrupt withdrawal from etizolam. This is particularly relevant given etizolam's short half life relative to benzodiazepines such as diazepam resulting in a more rapid drug level decrease in blood plasma levels. In a study that compared the effectiveness of etizolam, alprazolam, and bromazepam for the treatment of generalized anxiety disorder, all three drugs retained their effectiveness over 2 weeks, but etizolam became more effective from 2 weeks to 4 weeks. Administering.5 mg etizolam twice daily did not induce cognitive deficits over 3 weeks when compared to placebo. When multiple doses of etizolam, or lorazepam, were administered to rat neurons, lorazepam caused downregulation of alpha-1 benzodiazepine binding sites, while etizolam caused an increase in alpha-2 benzodiazepine binding sites. Tolerance to the anticonvulsant effects of lorazepam was observed, but no significant tolerance to the anticonvulsant effects of etizolam was observed. Etizolam therefore has a reduced liability to induce tolerance, and dependence, compared with classic benzodiazepines.
Pharmacology
Etizolam, a thienodiazepine derivative, is absorbed fairly rapidly, with peak plasma levels achieved between 30 minutes and 2 hours. It has a mean elimination half life of about 3.5 hours. Etizolam possesses potent hypnotic properties, and is comparable with other short-acting benzodiazepines. Etizolam acts as a full agonist at the benzodiazepine receptor to produce its range of therapeutic and adverse effects. According to the Italian P.I. sheet, etizolam belongs to a new class of diazepines, thienotriazolodiazepines. This new class is easily oxidized, rapidly metabolized, and has a lower risk of accumulation, even after prolonged treatment. Etizolam has an anxiolytic action about 6 times greater than that of diazepam. Etizolam produces, especially at higher dosages, a reduction in time taken to fall asleep, an increase in total sleep time, and a reduction in the number of awakenings. During tests, there were no substantial changes in deep sleep; however, it may reduce REM sleep. In EEG tests of healthy volunteers, etizolam showed some similar characteristics to tricyclic antidepressants. Etizolam's main metabolites in humans are alpha-hydroxyetizolam and 8-hydroxyetizolam. Alpha-hydroxyetizolam is pharmacologically active and has a half-life of approximately 8.2 hours.
Interactions
and fluvoxamine slow down the rate of elimination of etizolam, leading to accumulation of etizolam, therefore increasing its pharmacological effects. Carbamazepine speeds up the metabolism of etizolam, resulting in reduced pharmacological effects.
Overdose
Cases of intentional suicide by overdose using etizolam in combination with GABA agonists have been reported. Although etizolam has a lower LD50 than certain benzodiazepines, the LD50 is still far beyond the prescribed or recommended dose. Flumazenil, a GABA antagonist agent used to reverse benzodiazepine overdoses, inhibits the effect of etizolam as well as classical benzodiazepines such as diazepam and chlordiazepoxide. Etizolam overdose deaths are rising - for instance, the National Records of Scotland report on drug-related deaths, implicated 548 deaths from 'street' Etizolam in 2018, almost double the number from 2017 and only six years from the first recorded death. The 548 deaths were 45% of all drug-related deaths in Scotland in 2018.
Society and culture
Brand names
Etilaam, Sedekopan, Etizest, Etizex, Pasaden or Depas
Etizolam is a Schedule 4 substance under the Poisons StandardJune 2018 as it is classed as a benzodiazepine derivative. A schedule 4 drug is outlined in the Poisons Act 1964 as "Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription."
Etizolam is not authorized by the FDA for medical use in the U.S. However, it currently remains unscheduled at the federal level and is legal for research purposes. As of March 2016, etizolam is a controlled substance in the following states: Alabama, Arkansas, Florida, Georgia, Louisiana, Mississippi, Texas, South Carolina, and Virginia. It is controlled in Indiana as of July 1, 2017. It is controlled in Ohio as of February 2018.
Misuse
Etizolam is a drug of potential misuse. Cases of etizolam dependence have been documented in the medical literature. However, conflicting reports from the World Health Organization, made public in 1991, dispute the misuse claims. Since 1991, cases of etizolam misuse and addiction have substantially increased, due to varying levels of accessibility and cultural popularity. Pills being sold as Xanax or other benzodiazepines that are illicitly manufactured may often contain etizolam rather than their listed ingredient
