TRIAZOLAM

'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.^[1]

Contents

History

Pharmacology

Dependence

Indications

Dosage

Side effects

Interactions

Contraindications

Pregnancy

Overdose

Legal status

External links

Footnotes

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Triazolam was temporarily withdrawn from the market in several countries because of concerns about serious side effects (mostly psychological) associated with high dosages of the drug.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.¹
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.¹
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 GABA_A receptor.^[2]

Dependence

Triazolam has a very high risk of dependency with chronic users often taking exceedingly high daily doses.^[3] 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.^[4]
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.^[5]
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 anesthesia¹ 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.^[6]
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.^[7]
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 overdose¹ 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.^[8]
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 presciption 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

1. Triazolam Wishart, David
2. [Chemical and pharmacologic aspects of benzodiazepines], Oelschläger H., , , Schweiz Rundsch Med Prax., 1989
3. [Prescription of tranquilizers and hypnotics in the municipality of Holbaek], Veje JO, , , Ugeskr Laeger., 1989
4. Rebound insomnia. A potential hazard following withdrawal of certain benzodiazepines., Kales A, , , JAMA : the journal of the American Medical Association., 1979
5. [Two cases of psychotic state following normal-dose benzodiazepine withdrawal], Terao T, , , J UOEH., 1988
6.
Anterograde amnesia in triazolam overdose despite flumazenil treatment: a case report.
7. Residual effects of hypnotics: epidemiology and clinical implications., Vermeeren A., , , CNS Drugs., 2004
8. List of psychotropic substances under international control