Triazolam

Triazolam, sold under the brand name Halcion among others, is a central nervous system (CNS) depressant tranquilizer of the triazolobenzodiazepine (TBZD) class, which are benzodiazepine (BZD) derivatives.[4] It possesses pharmacological properties similar to those of other benzodiazepines, but it is generally only used as a sedative to treat severe insomnia.[5] In addition to the hypnotic properties, triazolam's amnesic, anxiolytic, sedative, anticonvulsant, and muscle relaxant properties are pronounced as well.[6]

Triazolam was initially patented in 1970 and went on sale in the United States in 1982.[7] In 2017, it was the 289th most commonly prescribed medication in the United States, with more than one million prescriptions.[8]

Medical uses

Triazolam is usually used for short-term treatment of acute insomnia and circadian rhythm sleep disorders, including jet lag. It is an ideal benzodiazepine for this use because of its fast onset of action and short half-life. It puts a person to sleep for about 1.5 hours, allowing its user to avoid morning drowsiness. Triazolam is also sometimes used as an adjuvant in medical procedures requiring anesthesia[9] or to reduce anxiety during brief events, such as MRI scans and nonsurgical dental procedures. Triazolam is ineffective in maintaining sleep due to its short half-life, with quazepam showing superiority.[10]

Triazolam is frequently prescribed as a sleep aid for passengers travelling on short- to medium-duration flights. If this use is contemplated, the user avoiding the consumption of alcohol is especially important, as is trying a ground-based "rehearsal" of the medication to ensure that the side effects and potency of this medication are understood by the user prior to using it in a relatively more public environment (as disinhibition can be a common side effect, with potentially severe consequences). Triazolam causes anterograde amnesia, which is why so many dentists administer it to patients undergoing even minor dental procedures. This practice is known as sedation dentistry.[11]

Side effects

Adverse drug reactions associated with the use of triazolam include:

Triazolam, although a short-acting benzodiazepine, may 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, psychomotor impairment, and diminished 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.[13] Confusion and amnesia have been reported.[14] Triazolam use can shift the circadian cycle.[15]

In September 2020, the US Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.[16]

• Relatively common (>1% of patients): somnolence, dizziness, lightheadedness, coordination problems
• Less common (0.9% to 0.5% of patients): euphoria, tachycardia, fatigue, delirium, memory impairment, cramps/pain, depression, visual disturbances
• Rare (<0.5% of patients): constipation, taste alteration, diarrhea, dry mouth, dermatitis/allergy, abnormal dreams or nightmares, insomnia (paradoxical), paresthesia, tinnitus, dysesthesia, weakness, nasal/sinus congestion[12]

Interactions

Ketoconazole and itraconazole have a profound effect on the pharmacokinetics of triazolam, leading to greatly enhanced effects.[24] Anxiety, tremor, and depression have been documented in a case report following administration of nitrazepam and triazolam. Co-administration of benzodiazepine drugs at therapeutic doses with erythromycin may cause serious psychotic symptoms, especially in those with other physical complications.[25] Caffeine reduces the effectiveness of triazolam.[26] Other important interactions include cimetidine, diltiazem, fluconazole, grapefruit juice, isoniazid, itraconazole, nefazodone, rifampicin, ritonavir, and troleandomycin.[27][28] Triazolam should not be administered to patients on efavirenz/emtricitabine/tenofovir (Atripla).[29]

Overdose

Symptoms of an overdose[9] include:

Death can occur from triazolam overdose, but is more likely to occur in combination with other depressant drugs such as opioids, alcohol, or tricyclic antidepressants.[30]

• Coma
• Hypoventilation (respiratory depression)
• Somnolence (drowsiness)
• Slurred speech
• Seizures[12]

Pharmacology

Like other benzodiazepines, triazolam enhances the inhibitory effects of the neurotransmitter GABA by binding to the allosteric benzodiazepine receptor on GABAA receptor complexes.[31]

Triazolam is short-acting, is lipophilic, and is metabolized hepatically via oxidative pathways. Triazolam produces one short-acting active metabolite, alpha-hydroxytriazolam, which is suspected to be of minor clinical significance.[32] The half-life of triazolam is only 2 hours making it a very short acting benzodiazepine drug.[33] It has anticonvulsant effects on brain function.[34]

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