Triazolam
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| Pregnancy category |
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| Routes of administration | Oral |
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| Legal status |
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| Pharmacokinetic data | |
| Bioavailability | 44% (oral) 53% (sublingual) |
| Metabolism | Hepatic |
| Elimination half-life | 1.5-5.5 hours |
| Excretion | Renal |
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| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.044.811 |
| Chemical and physical data | |
| Formula | C17H12Cl2N4 |
| Molar mass | 343.2 g·mol−1 |
Triazolam (marketed under brand names Halcion®, Novodorm®, Songar®) is a benzodiazepine derivative drug. It possesses pharmacological properties similar to that of other benzodiazepines, but it is generally only used as a sedative.[2]
History
Triazolam was temporarily withdrawn from the market in several countries because of concerns about serious side effects (mostly psychological) associated with high dosages of the drug. Its use at lower doses has been deemed safe by the American Food and Drug Administration (FDA) and most other countries.[2]
However, Triazolam has remained banned in the UK since 1991, when the Committee on the Safety of Medicines (CSM) concluded that it caused a higher frequency of psychiatric side-effects than other hypnotics.
It has been alleged to cause strange behavior and in some instances violent reactions. However, these allegations are anecdotal in nature. While triazolam as the instigator of violence has been accepted in some trials (particularly criminal offenses of defendants without violent tendencies) the anecdotal evidence has not risen to the level that the FDA has determined it statistically verifiable.
Pharmacology
The pharmacological effects of triazolam are similar to those of most other benzodiazepines. Triazolam does not generate active metabolites.[2] Triazolam is a short acting benzodiazepine, is lipophilic and is metabolised hepatically via oxidative pathways. The main pharmacological effects of triazolam are the enhancement of the neurotransmitter, GABA at the GABAA receptor.[3]
Dependence
Triazolam has a very high risk of dependency with chronic users often taking exceedingly high daily doses.[4] Regular use of triazolam may cause a hypnotic drug dependence. Withdrawal symptoms typically appear when triazolam dosage is reduced or stopped altogether. Withdrawal symptoms including a worsening of insomnia compared to baseline typically occurs after discontinuation of triazolam even after short term single nightly dose therapy.[5]
Abrupt withdrawal after long term use from therapeutic doses of triazolam may result in a severe withdrawal syndrome. Reports in the medical literature report of psychotic states developing after abrupt withdrawal from triazolam. The withdrawal symptoms included auditory hallucinations and visual cognitive disorder. Gradual and careful reduction of the dosage was recommended to prevent severe withdrawal syndromes from developing.[6] See (benzodiazepine withdrawal syndrome).
Indications
Triazolam is usually used for short term treatment of acute insomnia including jet lag. It is an ideal benzodiazepine for this use, due to the fact that its fast onset of action and short half-life (approximately 3 hours) allows its user to avoid morning drowsiness. Triazolam is also sometimes used as an adjuvant in medical procedures requiring anesthesia[2] or to reduce anxiety during brief events like MRI scans.
Dosage
Dosages for triazolam are significantly lower than other benzodiazepines, and should be individualized depending on the needs of the patient. For insomnia, 0.125mg to 0.25mg are given at bedtime. Up to 0.5mg may be needed for resistant individuals. Dosages exceeding 0.5mg are generally unsafe.
Side effects
Triazolam causes transient anterograde amnesia (failure to remember new things, especially during the time the medication is in the user's system) at dosages higher than 1-3mg.[7] Triazolam although a short acting benzodiazepine may still cause residual impairment into the next day, especially the next morning. A meta-analysis demonstrated that residual 'hangover' effects after nighttime administration of triazolam such as sleepiness, impaired psychomotor and cognitive functions may persist into the next day which may impair the ability of users to drive safely and increase risks of falls and hip fractures.[8]
Fuzzy, clouded thoughts, as well as incomprehension of the passage of time, may occur in lower doses as well as higher ones. In some cases, violent and unpredictable mood swings can occur.
Interactions
Triazolam will have interactions similar to those seen with other benzodiazepine and other categories of anxiolytic/hypnotic.
As with most prescription medications, caution is advised when combining other drugs with Triazolam.
Contraindications
Pregnancy
Halcion belongs to the Pregnancy Category X of the FDA [1]. This means that it is known to have the potential to cause birth defects.
Overdose
Symptoms of overdose[2] include
- Somnolence (drowsiness)
- Impaired motor function
- Slurred speech
- Coma
- Hypoventilation (respiratory depression)
Legal status
Internationally, triazolam is a Schedule IV drug under the Convention on Psychotropic Substances.[9]
In Hong Kong, Triazolam is regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. It can only be used legally by health professionals and for university research purporses. The substance can be given by pharmacists under a prescription. Anyone who supplies the substance without prescription can be fined $10000 (HKD). The penalty for trafficking or manufacturing the substance is a $5,000,000 (HKD) fine and life imprisonment. Possession of the substance for consumption without license from the Department of Health is illegal with a $1,000,000 (HKD) fine and/or 7 years of jail time. More information can be found: [2]
External links
- Medlineplus.org - Triazolam
- Rx-List.com - Triazolam
- Inchem.org - Triazolam
- MentalHealth.com - Triazolam
- Halcion controversy - Newsweek August 19, 1991 - Sweet Dreams or Nightmare?
Footnotes
- ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
- ^ a b c d e Wishart, David (2006). "Triazolam". DrugBank. Retrieved 2006-03-23.
- ^ Oelschläger H. (1989-07-04). "Chemical and pharmacologic aspects of benzodiazepines". Schweiz Rundsch Med Prax. 78 (27–28): 766–72. PMID 2570451.
{{cite journal}}: Check date values in:|date=(help); Cite has empty unknown parameter:|coauthors=(help) - ^ Veje JO (1989-08-21). "Prescription of tranquilizers and hypnotics in the municipality of Holbaek". Ugeskr Laeger. 151 (34): 2134–6. PMID 2773144.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Kales A (1979-04-20). "Rebound insomnia. A potential hazard following withdrawal of certain benzodiazepines". JAMA : the Journal of the American Medical Association. 241 (16): 1692–5. PMID 430730.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Terao T (1988-09-01). "Two cases of psychotic state following normal-dose benzodiazepine withdrawal". J UOEH. 10 (3): 337–40. PMID 2902678.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ "Anterograde amnesia in triazolam overdose despite flumazenil treatment: a case report". Hum Exp Toxicol. 1992 Jul;11(4):289-90. Retrieved 2006-06-25.
- ^ Vermeeren A. (2004). "Residual effects of hypnotics: epidemiology and clinical implications". CNS Drugs. 18 (5): 297–328. PMID 15089115.
{{cite journal}}: Cite has empty unknown parameter:|coauthors=(help) - ^ "List of psychotropic substances under international control" (PDF). Green list. International Narcotics Control Board. YEAR. Retrieved 2006-03-23.
{{cite web}}: Check date values in:|year=(help)CS1 maint: year (link)