Diazepam for Anxiety, Seizures, Muscle Spasm, and Alcohol Withdrawal

Diazepam is a benzodiazepine medication available in tablets, injectable solution, and rectal gel formulations. It is used to manage anxiety disorders, relieve muscle spasms, control seizures, and ease symptoms associated with acute alcohol withdrawal. Each formulation has specific approved uses and dosing considerations, with safety warnings regarding dependence, withdrawal, and interactions with other central nervous system depressants.

Diazepam is approved for:

• Management of anxiety disorders or short-term relief of anxiety symptoms in adults and pediatric patients over 6 months of age (for tablets).
• Symptomatic relief of acute agitation, tremor, delirium tremens, and hallucinosis related to acute alcohol withdrawal.
• Adjunctive treatment of skeletal muscle spasm linked to local pathology, upper motor neuron disorders (e.g., cerebral palsy, paraplegia), athetosis, stiff-man syndrome, and tetanus (especially with injectable diazepam).
• Adjunctive therapy in convulsive disorders, including status epilepticus (especially injectable and rectal gel forms).
• Preprocedural sedation, including prior to endoscopic and surgical procedures, and prior to cardioversion (injectable form).
• The rectal gel formulation is specifically indicated for acute treatment of intermittent, stereotypic seizure clusters in patients with epilepsy aged 2 years and older.

Diazepam

Diazepam enhances the effects of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the brain. By binding to GABA A receptors, it increases chloride ion influx into neurons, stabilizing them and reducing excessive excitability. This action produces anxiolytic, sedative, muscle-relaxant, anticonvulsant, and amnestic effects, helping to control anxiety, muscle spasms, seizures, and agitation.

Tablets (Oral)

• Adults: Anxiety - 2 mg to 10 mg, 2 to 4 times daily; acute alcohol withdrawal - 10 mg 3-4 times in first 24 hours, then 5 mg 3-4 times daily; muscle spasm and convulsive disorders - 2 mg to 10 mg, 2 to 4 times daily.
• Geriatrics or debilitated: Initially 2 mg to 2.5 mg once or twice daily, increase gradually as tolerated.
• Pediatrics (over 6 months): Initially 1 mg to 2.5 mg, 3 to 4 times daily, titrate as needed.
• Discontinuation: Use gradual taper to reduce dosage and avoid withdrawal.

Injection, Solution (Intramuscular or Intravenous)

• Dosing individualized; typically 2 mg to 20 mg depending on indication.
• Anxiety: 2-10 mg IM or IV, repeated every 3-4 hours as needed.
• Acute alcohol withdrawal: 10 mg initially IM or IV, then 5-10 mg every 3-4 hours as needed.
• Muscle spasm and tetanus: 5-10 mg IM/IV initially, possibly larger doses for tetanus.
• Status epilepticus: 5-10 mg IV initially; may repeat up to 30 mg total dose; in children 3 months - 17 years: 0.2 mg/kg up to 8 mg IV slow push, repeat as needed.
• Premedication for surgery and cardioversion with dosing adjusted accordingly.
• Use slow IV injection over at least 1 minute per 5 mg dose; avoid small veins and intra-arterial injection.
• Lower doses recommended in elderly and debilitated patients.

Rectal Gel

• For acute treatment of seizure clusters in epilepsy patients aged 2 years and older.
• Dosing based on age and weight with approximate doses of 0.5 mg/kg (2-5 years), 0.3 mg/kg (6-11 years), or 0.2 mg/kg (12 years and older), rounded to available unit doses.
• May repeat one additional dose 4 to 12 hours after first dose if needed.
• Limit use to no more than five episodes per month and no more than one episode every five days.
• Dosage adjustment in elderly and debilitated patients advised.

• Known hypersensitivity to diazepam.
• Acute narrow-angle glaucoma.
• Myasthenia gravis (tablets).
• Severe respiratory insufficiency (tablets).
• Severe hepatic insufficiency (tablets).
• Sleep apnea syndrome (tablets).
• Use is not established and not recommended in pediatric patients under 6 months (tablets and rectal gel).

Boxed Warnings and Serious Precautions

• Concomitant Use with Opioids: Combining diazepam with opioids can cause profound sedation, respiratory depression, coma, and death. Use together only when alternatives are inadequate, at lowest doses and shortest duration, with close monitoring.
• Abuse, Misuse, Addiction: Diazepam has risks of abuse and addiction that can lead to overdose or death, often worsened by concomitant use of alcohol, opioids, or illicit substances. Assess patients for risk and counsel accordingly.
• Dependence and Withdrawal: Prolonged use may cause physical dependence. Abrupt discontinuation or rapid dose reduction can cause life-threatening withdrawal symptoms including seizures. Taper dose gradually.
• Respiratory Depression and CNS Depression: Risk increased with co-use of other CNS depressants (including alcohol). Monitor for sedation and respiratory problems.
• Pediatric Use: Not recommended under 6 months of age (tablets and gel). Injection safety not established in neonates; risk of prolonged CNS depression.
• Pregnancy: Use late in pregnancy may cause neonatal sedation and withdrawal. Avoid use in first trimester due to possible risk of congenital malformations.
• Patients with Certain Conditions: Contraindicated in acute narrow-angle glaucoma, myasthenia gravis, severe respiratory or hepatic insufficiency, and sleep apnea syndrome.
• Use in Psychiatric Patients: Not recommended as a substitution for appropriate treatment in psychotic patients.
• Injection-specific: Avoid intra-arterial administration; use slow injection; caution in elderly and ill patients; have resuscitation equipment ready.

Common Side Effects

• Drowsiness, fatigue, muscle weakness, ataxia.
• Somnolence (up to 23% with rectal gel).
• Dizziness, headache, blurred vision, diplopia.
• Nausea, constipation, dry mouth, changes in salivation.

Less Common or Serious Side Effects

• Confusion, depression, dysarthria, slurred speech, tremor, vertigo.
• Psychiatric/paradoxical reactions: agitation, restlessness, aggression, hallucinations, insomnia, nightmares, rage. More common in children and elderly.
• Hypotension, bradycardia, cardiovascular collapse (injection).
• Phlebitis and venous thrombosis at injection site.
• Neutropenia and jaundice (rare; monitor labs in long-term use).
• Risk of falls and fractures, especially with concomitant sedatives or alcohol and in elderly.
• Withdrawal symptoms on abrupt discontinuation: seizures, irritability, tremors, hyperreflexia.

• Opioids: Increased risk of sedation and respiratory depression; use lowest effective doses and monitor closely.
• Other CNS Depressants: Including alcohol, barbiturates, antipsychotics, hypnotics, antihistamines, MAO inhibitors, and antidepressants; co-use may potentiate sedation and respiratory depression.
• Antacids: May reduce diazepam peak concentration and delay absorption but do not affect overall absorption.
• CYP3A and CYP2C19 Inhibitors: Such as cimetidine, ketoconazole, fluvoxamine, fluoxetine, and omeprazole can increase diazepam levels, prolonging sedation.
• Phenytoin: Diazepam may decrease phenytoin metabolism.
• Valproate: May potentiate CNS depressant effects of diazepam (gel formulation).
• Other Psychotropic Agents: Careful consideration if combined with narcotics, phenothiazines, barbiturates, and antidepressants due to additive CNS effects.

Pregnancy

Use during the first trimester is generally avoided due to a suggested increased risk of congenital malformations. Diazepam crosses the placenta, and use late in pregnancy can cause neonatal sedation, respiratory depression, hypotonia, and withdrawal symptoms including irritability and feeding difficulties. Monitor neonates exposed to diazepam during pregnancy.

Lactation

Diazepam and its metabolites pass into breast milk at concentrations approximately one tenth of maternal plasma levels. Breastfeeding is not recommended during treatment.