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Systematic (IUPAC) name
Clinical data
Trade names Etilaam, Etizest
Routes of
Oral, sublingual, rectal
Legal status
Legal status
  • DE: Anlage III (Prescription only)
  • UK: Unscheduled
  • US: Schedule I in Alabama, Arkansas, Florida, Mississippi, and Virginia, Schedule IV in Georgia; not FDA approved. Unscheduled in the remaining states.
Pharmacokinetic data
Bioavailability 93%
Metabolism Hepatic
Biological half-life

6.2 hours[1]

(main metabolite is 8.2 hours)
Excretion Renal
CAS Number 40054-69-1 YesY
ATC code N05BA19 (WHO)
PubChem CID 3307
ChemSpider 3191 YesY
KEGG D01514 YesY
Chemical data
Formula C17H15ClN4S
Molar mass 342.07 g/mol
 NYesY (what is this?)  (verify)

Etizolam (marketed under the brand name Etilaam, Etizola, Sedekopan, Etizest, Pasaden or Depas) is a benzodiazepine analog. The etizolam molecule differs from a benzodiazepine in that the benzene ring has been replaced by a thiophene ring and triazole ring has been fused, making the drug a thienotriazolodiazepine.[2][3] It possesses amnesic, anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties.[4]



  • Anxiety disorders associated with depression: 1 mg two to three times a day (maximum 3 mg per day)
  • For panic disorder (associated with agoraphobia): 0.5 mg two times per day (maximum 1 mg per day)
  • For insomnia: 1–2 mg once daily before bedtime[6]

A 1 mg dose of etizolam is approximately equivalent to a 10 mg dose of diazepam (Valium) or a 0.5 mg dose of alprazolam (Xanax), though all three are of differing biological half-lives; see list of benzodiazepines.

Side effects[edit]

Very Rare

Tolerance, dependence and withdrawal[edit]

Abrupt or rapid withdrawal from etizolam, as with benzodiazepines, may result in the appearance of the benzodiazepine withdrawal syndrome, including rebound insomnia.[9] Neuroleptic malignant syndrome, a rare event in benzodiazepine withdrawal, has been documented in a case of abrupt withdrawal from etizolam.[10] 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.[11]

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, a type of reverse tolerance.[12] Administering .5 mg etizolam twice daily did not induce cognitive deficits over 3 weeks when compared to placebo.[13]

When multiple doses of etizolam, or lorazepam, were administered to rat neurons, lorazepam caused downregulation of alpha-1 benzodiazepine binding sites (tolerance/dependence), while etizolam caused an increase in alpha-2 benzodiazepine binding sites (reverse tolerance to anti-anxiety effects).[14] Tolerance to the anticonvulsant effects of lorazepam was observed, but no significant tolerance to the anticonvulsant effects of etizolam was observed.[14] Etizolam therefore has a reduced liability to induce tolerance, and dependence, compared with classic benzodiazepines.[14]

Contraindications and special caution[edit]

Etizolam is metabolized by the liver and is contraindicated in those with severely impaired hepatic function. It may impair the ability to drive and operate machinery so caution should be applied. Elderly patients should start on a lower dose as they are more susceptible to the sedative effects of etizolam. It is not recommended to be taken during pregnancy or breastfeeding.[6]

Etizolam can increase the sedative and antidepressant actions of other medication such as neuroleptics, analgesics, anaesthetics, antiepileptics, sedatives and first-generation antihistamines. Co-administration with these medications should be avoided unless instructed by a medical professional. Alcohol should also be avoided.[6]

Drugs inhibiting the enzymes CYP2C19 and CYP3A4, such as fluvoxamine, should not be taken concurrently as etizolam can increase the plasma levels of these enzymes.[6]


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.[15] Etizolam possesses potent hypnotic properties,[16] and is comparable with other short-acting benzodiazepines.[15] Etizolam acts as a full agonist at the benzodiazepine receptor to produce its range of therapeutic and adverse effects.[17] Similar to other benzodiazepines (exceptions include quazepam) etizolam binds non-selectively to benzodiazepine receptor subtypes.[dubious ][18]

In addition, etizolam, unlike most benzodiazepines (some of which can increase levels of estradiol), has prolactogenic effects, leading to an increase in blood levels of prolactin.[19]

According to the Italian P.I. sheet[citation needed], 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.[1]

Legal status[edit]

United States[edit]

Etizolam is not authorized by the FDA for medical use in the U.S. However, it currently remains unscheduled and is legal for research purposes. As of March 2016, etizolam is a controlled substance in the following states: Alabama, Arkansas,[20] Florida,[21] Mississippi,[22] Virginia,[23] and Georgia.[24]

United Kingdom[edit]

Unlike other thienodiazepines such as brotizolam and clotiazepam, etizolam is not controlled under the Misuse of Drugs Act 1971 or licensed as a medicine in the United Kingdom.[25] Etizolam is, however, in scope of the Psychoactive Substances Act 2016, thus making its importation and sale illegal across the United Kingdom.[26]


Etizolam was controlled in Germany in July 2013.[27]


Etizolam also called Depas, is restricted as a benzodiazepine analogs in Japan on Oct, 2016.


Itraconazole and fluvoxamine slow down the rate of elimination of etizolam, leading to accumulation of etizolam, therefore increasing its pharmacological effects.[28][29] Carbamazepine speeds up the metabolism of etizolam, resulting in reduced pharmacological effects.[30]

Etizolam, similarly to other GABAergic agonists including benzodiazepines has a strong synergistic effect with ethanol and the consequences of co-ingestion of the two drugs can drastically compound the side effects of either drug.[medical citation needed] This can result in (among other effects) anterograde amnesia (blackouts) and severe respiratory depression which in extreme cases can lead to death.[medical citation needed]


Cases of intentional suicide by overdose using etizolam in combination with GABA agonists have been reported.[31] 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.[32]


Etizolam is a drug of potential abuse. Cases of etizolam dependence have been documented in the medical literature.[33] However, conflicting reports from the World Health Organization, made public in 1991, dispute the abuse claims.[34]

See also[edit]


  1. ^ a b c "Depas". Retrieved October 31, 2015. 
  2. ^ Niwa T, Shiraga T, Ishii I, Kagayama A, Takagi A (September 2005). "Contribution of human hepatic cytochrome p450 isoforms to the metabolism of psychotropic drugs" (PDF). Biol. Pharm. Bull. 28 (9): 1711–6. doi:10.1248/bpb.28.1711. PMID 16141545. 
  3. ^ Catabay, A.; Taniguchi, M.; Jinno, K.; Pesek, J. J.; Williamsen, E. (1 March 1998). "Separation of 1,4-Benzodiazepines and Analogues Using Cholesteryl-10-Undecenoate Bonded Phase in Microcolumn Liquid Chromatography". Journal of Chromatographic Science. 36 (3): 113. doi:10.1093/chromsci/36.3.111. 
  4. ^ Mandrioli R, Mercolini L, Raggi MA (October 2008). "Benzodiazepine metabolism: an analytical perspective". Curr. Drug Metab. 9 (8): 827–44. doi:10.2174/138920008786049258. PMID 18855614. 
  5. ^ Lopedota A, Cutrignelli A, Trapani A, et al. (May 2007). "Effects of different cyclodextrins on the morphology, loading and release properties of poly (DL-lactide-co-glycolide)-microparticles containing the hypnotic agent etizolam". J Microencapsul. 24 (3): 214–24. doi:10.1080/02652040601058152. PMID 17454433. 
  6. ^ a b c d Pharmaceuticals, Intas. "Etilaam - .25mg, .50mg,.1mg". Etilaam's prescribing info sheet for doctors in India. Intas Pharmaceuticals. 
  7. ^ Wakakura M, Tsubouchi T, Inouye J (March 2004). "Etizolam and benzodiazepine induced blepharospasm". J. Neurol. Neurosurg. Psychiatr. 75 (3): 506–7. doi:10.1136/jnnp.2003.019869. PMC 1738986free to read. PMID 14966178. 
  8. ^ Kuroda K, Yabunami H, Hisanaga Y (January 2002). "Etizolam-induced superficial erythema annulare centrifugum". Clin. Exp. Dermatol. 27 (1): 34–6. doi:10.1046/j.0307-6938.2001.00943.x. PMID 11952667. 
  9. ^ Hirase M, Ishida T, Kamei C (November 2008). "Rebound insomnia induced by abrupt withdrawal of hypnotics in sleep-disturbed rats". Eur. J. Pharmacol. 597 (1–3): 46–50. doi:10.1016/j.ejphar.2008.08.024. PMID 18789918. 
  10. ^ Kawajiri M, Ohyagi Y, Furuya H, et al. (February 2002). "[A patient with Parkinson's disease complicated by hypothyroidism who developed malignant syndrome after discontinuation of etizolam]". Rinsho Shinkeigaku (in Japanese). 42 (2): 136–9. PMID 12424963. 
  11. ^
  12. ^ Bertolino, A; Mastucci, E; Porro, V; Corfiati, L; Palermo, M; Ecari, U; Ceccarelli, G (1989). "Etizolam in the treatment of generalized anxiety disorder: A controlled clinical trial". The Journal of international medical research. 17 (5): 455–60. PMID 2572494. 
  13. ^ De Candia, MP; Di Sciascio, G; Durbano, F; Mencacci, C; Rubiera, M; Aguglia, E; Garavini, A; Bersani, G; Di Sotto, A; Placidi, G; Cesana, BM (2009). "Effects of treatment with etizolam 0.5 mg BID on cognitive performance: A 3-week, multicenter, randomized, double-blind, placebo-controlled, two-treatment, three-period, noninferiority crossover study in patients with anxiety disorder". Clinical therapeutics. 31 (12): 2851–9. doi:10.1016/j.clinthera.2009.12.010. PMID 20110024. 
  14. ^ a b c Sanna, E; Busonero, F; Talani, G; Mostallino, MC; Mura, ML; Pisu, MG; MacIocco, E; Serra, M; Biggio, G (2005). "Low tolerance and dependence liabilities of etizolam: Molecular, functional, and pharmacological correlates". European Journal of Pharmacology. 519 (1–2): 31–42. doi:10.1016/j.ejphar.2005.06.047. PMID 16107249. 
  15. ^ a b Fracasso C, Confalonieri S, Garattini S, Caccia S (1991). "Single and multiple dose pharmacokinetics of etizolam in healthy subjects". Eur. J. Clin. Pharmacol. 40 (2): 181–5. doi:10.1007/BF00280074. PMID 2065698. 
  16. ^ Nakamura J, Mukasa H (December 1992). "Effects of thienodiazepine derivatives, etizolam and clotiazepam on the appearance of Fm theta". Jpn. J. Psychiatry Neurol. 46 (4): 927–31. doi:10.1111/j.1440-1819.1992.tb02862.x. PMID 1363923. 
  17. ^ Yakushiji T, Fukuda T, Oyama Y, Akaike N (November 1989). "Effects of benzodiazepines and non-benzodiazepine compounds on the GABA-induced response in frog isolated sensory neurones". Br. J. Pharmacol. 98 (3): 735–40. doi:10.1111/j.1476-5381.1989.tb14600.x. PMC 1854765free to read. PMID 2574062. 
  18. ^ Ozawa M, Nakada Y, Sugimachi K, et al. (March 1994). "Pharmacological characterization of the novel anxiolytic beta-carboline abecarnil in rodents and primates". Jpn. J. Pharmacol. 64 (3): 179–87. doi:10.1254/jjp.64.179. PMID 7912751. 
  19. ^ Kaneda Y (2000). "Short Communication: Prolactogenic effects of etizolam". Neuro Endocrinol. Lett. 21 (6): 475–476. PMID 11335869. 
  20. ^
  21. ^
  22. ^
  23. ^ "18VAC110-20-322. Placement of Chemicals in Schedule I.". Commonwealth of Virginia. 2 December 2015. Retrieved 11 March 2016. 
  24. ^
  25. ^
  26. ^
  27. ^ and
  28. ^ Araki K, Yasui-Furukori N, Fukasawa T, et al. (August 2004). "Inhibition of the metabolism of etizolam by itraconazole in humans: evidence for the involvement of CYP3A4 in etizolam metabolism". Eur. J. Clin. Pharmacol. 60 (6): 427–30. doi:10.1007/s00228-004-0789-1. PMID 15232663. 
  29. ^ Suzuki Y, Kawashima Y, Shioiri T, Someya T (December 2004). "Effects of concomitant fluvoxamine on the plasma concentration of etizolam in Japanese psychiatric patients: wide interindividual variation in the drug interaction". Ther Drug Monit. 26 (6): 638–42. doi:10.1097/00007691-200412000-00009. PMID 15570188. 
  30. ^ Kondo S, Fukasawa T, Yasui-Furukori N, et al. (May 2005). "Induction of the metabolism of etizolam by carbamazepine in humans". Eur. J. Clin. Pharmacol. 61 (3): 185–8. doi:10.1007/s00228-005-0904-y. PMID 15776275. 
  31. ^ Nakamae T, Shinozuka T, Sasaki C, et al. (November 2008). "Case report: Etizolam and its major metabolites in two unnatural death cases". Forensic Sci. Int. 182 (1–3): e1–6. doi:10.1016/j.forsciint.2008.08.012. PMID 18976871. 
  32. ^ Woolverton WL, Nader MA, et al. (December 1995). "Case report: Effects of several benzodiazepines, alone and in combination with flumazenil, in rhesus monkeys trained to discriminate pentobarbital from saline.". Psychopharmacology (Berl). 122 (3): 230–236. doi:10.1007/BF02246544. PMID 8748392. 
  33. ^ Gupta S, Garg B (2014). "A case of etizolam dependence". Indian J Pharmacol. 46 (6): 655–656. doi:10.4103/0253-7613.144943. PMC 4264086free to read. PMID 25538342. 
  34. ^ WHO Expert Committee on Drug Dependence

External links[edit]