Anxiolytics. Benzodiazepine derivatives
ATC code: N05BA01 (Diazepam)
Brand names
Valium, Diastat, Valtoco, Diazepam Intensol
Allosteric GABA-A receptor modulator: enhances inhibitory GABA action. Anxiolytic, anticonvulsant, muscle relaxant, sedative. black box warning on respiratory depression and death when combined with opioids.
First line
Long-acting benzodiazepines (diazepam, chlordiazepoxide) are first-line for alcohol withdrawal management, prevention of delirium and seizures. Symptom-triggered dosing by CIWA-Ar: if score >8, give 10–20 mg diazepam orally or intravenously, repeat every 1–2 hours until sedation and CIWA-Ar reduction.
In severe hepatic impairment, lorazepam or oxazepam without active metabolites are preferred.
First line
Intravenous (0.15–0.2 mg/kg, max 10 mg) or rectal diazepam is one of the first-line agents for status epilepticus in adults and children per 2016. Lorazepam and midazolam are comparable in efficacy. Used immediately after a prolonged seizure (>5 minutes). If seizures persist 5 minutes after the first dose, repeat or move to second-line agents (fosphenytoin, valproate, levetiracetam).
In children, rectal diazepam (Diastat) is preferred when intravenous access is unavailable in the prehospital setting.
Sources
Second line
Benzodiazepines are used for short-term relief of acute anxiety or panic attacks, limited to 2–4 weeks. CG113 and Russian clinical guidelines emphasize avoiding long-term use due to dependence and tolerance risk. First-line drugs for anxiety disorders are SSRIs and SNRIs combined with CBT.
Avoid in patients with a history of substance use disorder. In elderly contraindicated per Beers Criteria 2023: risk of falls, fractures, and confusion.
Adjunct
Diazepam is used as a muscle relaxant for central spasticity (MS, spinal cord injury) and painful muscle spasms. Efficacy demonstrated in small RCTs. Modern practice prefers baclofen and tizanidine due to less sedation and lower dependence risk.
Not recommended
Benzodiazepines are not standard therapy for chronic anxiety and insomnia. CG113, , and Russian guidelines limit benzodiazepine courses to 2–4 weeks. Long-term use causes tolerance, physical dependence, and cognitive impairment. Discontinuation produces withdrawal with anxiety, insomnia, and seizure risk.
Not recommended
In elderly patients with dementia, benzodiazepines are not used for behavioral disturbance. Beers Criteria 2023 lists benzodiazepines as potentially inappropriate in older adults: increased risk of falls, hip fractures, delirium, and paradoxical aggression. Preferred options are non-pharmacological strategies and, if necessary, low-dose atypical antipsychotics.
Additive CNS depression and respiratory depression. Alcohol increases fatal benzodiazepine overdose risk. Full alcohol abstinence required; if not feasible – switch to another anxiolytic class.
Source: FDA: Valium (diazepam) prescribing information (2021)
1 pair found. Sorted from critical to minor.
Mechanism
Аддитивная депрессия и дыхания. black box warning по сочетанию опиоидов с бензодиазепинами.
Management
Избегать. Если без сочетания нельзя – минимальные дозы, инструктировать пациента о признаках передозировки, рассмотреть налоксон в домашней аптечке.
Boxed warning
FDA boxed warning (2020): risk of respiratory depression, sedation, coma, and death when benzodiazepines are combined with opioids. Additional warning: risk of abuse, dependence, and withdrawal. Use the lowest effective dose for the shortest duration; taper gradually on discontinuation.
diazepam is evaluated for the following indications with varying evidence strength: Status epilepticus (evidence tier A), Alcohol withdrawal syndrome (evidence tier A), Muscle spasticity (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of diazepam (≥ 1 in 100): Sedation, drowsiness, fatigue, Ataxia, impaired coordination, Anterograde amnesia, Reduced attention, Muscle weakness. See the Safety section for uncommon and serious reactions.
FDA category D. FDA category D. First-trimester use is associated with increased risk of cleft palate; third-trimester use with floppy infant syndrome and neonatal withdrawal. Prescribed only when benefit clearly outweighs risk, after obstetric consultation.
Passes into breast milk. Long-term use is discouraged due to accumulation in the infant (sedation, poor feeding). Single doses are acceptable with infant monitoring.
diazepam is contraindicated in: Hypersensitivity to benzodiazepines; Acute angle-closure glaucoma; Myasthenia gravis; Severe respiratory insufficiency; Sleep apnea syndrome. Full list in the Safety section.
FDA category D. First-trimester use is associated with increased risk of cleft palate; third-trimester use with floppy infant syndrome and neonatal withdrawal. Prescribed only when benefit clearly outweighs risk, after obstetric consultation.
Passes into breast milk. Long-term use is discouraged due to accumulation in the infant (sedation, poor feeding). Single doses are acceptable with infant monitoring.
FDA boxed warning (2020): risk of respiratory depression, sedation, coma, and death when benzodiazepines are combined with opioids. Additional warning: risk of abuse, dependence, and withdrawal. Use the lowest effective dose for the shortest duration; taper gradually on discontinuation.
physical dependence develops after courses over 4 weeks. Abrupt discontinuation causes severe withdrawal, sometimes with seizures.
first-line therapy for chronic insomnia is CBT-I, not benzodiazepines. Long-term benzodiazepine use reduces sleep quality and causes daytime drowsiness.
reaction and concentration are impaired for 24–48 hours after a dose because active metabolites have a long half-life.