Diazepam (Valium)

Class

Benzodiazepine

Mechanism

Facilitates GABA-A receptor activity by increasing the frequency of chloride channel opening, enhancing inhibitory neurotransmission and producing anxiolytic, muscle relaxant, anticonvulsant, and sedative effects.

FDA-Approved Use

Anxiety disorders, alcohol withdrawal symptoms, muscle spasms, seizure disorders (including adjunctive therapy for status epilepticus)

Off-Label Use

Acute agitation, status epilepticus (IV/rectal), spasticity associated with neurological conditions such as multiple sclerosis (MS) or cerebral palsy

Formulation

Oral tablets, oral solution, rectal gel, injectable

Titration

Start at 2–5 mg orally twice daily; titrate gradually based on clinical response and tolerability

Dose Range

2–40 mg/day in divided doses

Kinetics

Rapid onset with a long elimination half-life (20–50 hours), extended further by active metabolites (e.g., desmethyldiazepam); highly lipophilic, leading to accumulation with chronic use

Common AEs

Sedation, fatigue, dizziness, impaired coordination, confusion, memory disturbances

Serious/Rare AEs

Tolerance, dependence, withdrawal seizures, respiratory depression (especially with opioids or other CNS depressants), cognitive impairment, falls

Monitoring

Monitor for sedation, cognitive and motor effects, fall risk (especially in elderly), hepatic function in liver disease, and signs of misuse or withdrawal

Black Box Warning

Concomitant use with opioids can result in profound sedation, respiratory depression, coma, and death. Risk of dependence, abuse, and withdrawal syndrome with prolonged use.

Considerations

Use with heightened caution in elderly adults and individuals with dementia due to increased risks of falls, delirium, and sedation-related complications. In hepatic impairment, prolonged half-life and metabolite accumulation may occur; dose adjustments and careful monitoring are recommended. Long-acting properties may be advantageous in alcohol withdrawal or seizure protocols but increase risks in cognitively or medically vulnerable patients.