Benzodiazepine

Benzodiazepines
Drug class
Structural formula of benzodiazepines.
Class identifiers
Use	Anxiety disorders, seizures, muscle spasms, panic disorder
ATC code	N05BA
Mode of action	GABAA receptor
Legal status
In Wikidata

Benzodiazepines (BZD, BDZ, BZs), colloquially called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, insomnia, and seizures. The first benzodiazepine, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955 and was made available in 1960 by Hoffmann–La Roche, who soon followed with diazepam (Valium) in 1963.^[1] By 1977, benzodiazepines were the most prescribed medications globally; the introduction of selective serotonin reuptake inhibitors (SSRIs), among other factors, decreased rates of prescription, but they remain frequently used worldwide.^[2][3]

Benzodiazepines are depressants that enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABA_A receptor, resulting in sedative, hypnotic (sleep-inducing), anxiolytic (anti-anxiety), anticonvulsant, and muscle relaxant properties. High doses of many shorter-acting benzodiazepines may also cause anterograde amnesia and dissociation.^[4] These properties make benzodiazepines useful in treating anxiety, panic disorder, insomnia, agitation, seizures, muscle spasms, alcohol withdrawal and as a premedication for medical or dental procedures.^[5] Benzodiazepines are categorized as short, intermediate, or long-acting. Short- and intermediate-acting benzodiazepines are preferred for the treatment of insomnia; longer-acting benzodiazepines are recommended for the treatment of anxiety.^[6]

Benzodiazepines are generally viewed as safe and effective for short-term use—about two to four weeks^[7]—although cognitive impairment and paradoxical effects such as aggression or behavioral disinhibition can occur.^[8] According to the Department of Health (Victoria), long-term use can cause “impaired thinking or memory loss. anxiety and depression. irritability, paranoia, aggression, etc.”^[9] A minority of people have paradoxical reactions after taking benzodiazepines such as worsened agitation or panic.^[8] Benzodiazepines are associated with an increased risk of suicide due to aggression, impulsivity, and negative withdrawal effects.^[10] Long-term use is controversial because of concerns about decreasing effectiveness, physical dependence, benzodiazepine withdrawal syndrome, and an increased risk of dementia and cancer.^{[11][12][13][14]} The elderly are at an increased risk of both short- and long-term adverse effects,^[15][16] and as a result, all benzodiazepines are listed in the Beers List of inappropriate medications for older adults.^[17] There is controversy concerning the safety of benzodiazepines in pregnancy. While they are not major teratogens, uncertainty remains as to whether they cause cleft palate in a small number of babies and whether neurobehavioural effects occur as a result of prenatal exposure;^[18] they are known to cause withdrawal symptoms in the newborn.

Taken in overdose, benzodiazepines can cause dangerous deep unconsciousness, but they are less toxic than their predecessors, the barbiturates, and death rarely results when a benzodiazepine is the only drug taken. Combined with other central nervous system (CNS) depressants such as alcohol and opioids, the potential for toxicity and fatal overdose increases significantly.^[19][20] Benzodiazepines are commonly used recreationally and also often taken in combination with other addictive substances, and are controlled in most countries.^[21][22][23]