What are the anti-epileptic drugs (AEDs) used to manage acute seizures, including their doses and routes of administration?

From the Guidelines

For managing acute seizures, the most effective treatment approach is to use intravenous benzodiazepines as first-line agents, followed by second-line options such as fosphenytoin, levetiracetam, or valproate if seizures are refractory to benzodiazepines. The choice of anti-epileptic drug depends on various factors, including the severity of the seizure, patient's medical history, and potential side effects of the medication.

First-line Treatment Options

• Lorazepam (0.1 mg/kg IV at 2 mg/min, max 4 mg) is a preferred first-line treatment due to its longer duration of action 1.
• Alternatives include diazepam (0.15-0.2 mg/kg IV at 5 mg/min, max 10 mg) and midazolam (0.2 mg/kg IM/intranasal/buccal, max 10 mg).

Second-line Treatment Options

• If benzodiazepines fail, second-line options include fosphenytoin (20 mg PE/kg IV at 150 mg/min), valproate (40 mg/kg IV over 10 minutes), levetiracetam (60 mg/kg IV over 15 minutes, max 4500 mg), or phenobarbital (20 mg/kg IV at 50-100 mg/min) 1.
• Fosphenytoin, levetiracetam, or valproate may be used with similar efficacy as second-line agents 1.

Refractory Status Epilepticus

• For refractory status epilepticus, continuous infusions of midazolam (0.2 mg/kg bolus, then 0.1-2 mg/kg/hr), propofol (1-2 mg/kg bolus, then 2-10 mg/kg/hr), or pentobarbital (5-15 mg/kg bolus, then 0.5-5 mg/kg/hr) may be necessary.
• Monitoring vital signs, respiratory status, and having resuscitation equipment available is essential as these medications can cause respiratory depression and hypotension.

Maintenance Doses

• Maintenance doses of anticonvulsant drugs after resolution of status epilepticus are as follows:
  • Lorazepam 0.05 mg/kg (maximum 1 mg) i.v. every 8 hours for 3 doses 1.
  • Levetiracetam 15-30 mg/kg i.v. every 12 hours 1.
  • Phenobarbital 1–3 mg/kg i.v. every 12 hours 1.

From the FDA Drug Label

For intravenous infusion only (2.1) Do not dilute prior to its use (2.1) Administer dose-specific bag intravenously over 15-minutes (2.1) Initial Exposure to Levetiracetam Partial-Onset Seizures: Initial dose is 500 mg twice daily. Increase by 500 mg twice daily every 2 weeks to a maximum recommended dose of 1500 mg twice daily (2. 2).

For Status Epilepticus and Non-emergent Loading Dose: Adult loading dose is 10 to 15 mg/kg at a rate not exceeding 50 mg/min. ( 2 SECT 2.2) Pediatric loading dose is 15 to 20 mg/kg at a rate not exceeding 1 to 3 mg/kg/min or 50 mg/min, whichever is slower. ( 2 SECT 2. 8)

The anti-epileptic drugs used to manage acute seizures are Levetiracetam and Phenytoin.

• Levetiracetam: The dose is 500 mg twice daily, increased by 500 mg twice daily every 2 weeks to a maximum of 1500 mg twice daily, administered intravenously over 15 minutes 2.
• Phenytoin: The adult loading dose is 10 to 15 mg/kg at a rate not exceeding 50 mg/min, and the pediatric loading dose is 15 to 20 mg/kg at a rate not exceeding 1 to 3 mg/kg/min or 50 mg/min, whichever is slower, administered intravenously 3.

From the Research

Anti-Epileptic Drugs for Acute Seizures

The following anti-epileptic drugs are used to manage acute seizures:

• Benzodiazepines, which are the first-line treatment for status epilepticus worldwide due to their efficacy, tolerability, and rapid onset of action 4, 5
• Specific benzodiazepines used include:
  • Lorazepam
  • Midazolam
  • Diazepam
  • Clonazepam
  • Clobazam

Doses and Route of Administration

The doses and route of administration for these drugs are as follows:

• Lorazepam: typically administered intravenously, with a dose that is often lower than guideline recommendations 6
• Midazolam: can be administered intravenously, intramuscularly, or intranasally, with a dose that is often lower than guideline recommendations 6
• Diazepam: can be administered rectally, intravenously, or intramuscularly 5, 7
• Clonazepam and clobazam: can be used for seizure prophylaxis in patients with epilepsy refractory to multiple antiepileptic drugs, with clobazam preferred due to its affinity for the α2 subunit of the GABAA receptor 5
• The first-phase treatment for convulsive established status epilepticus is the immediate administration of full doses of benzodiazepines, while the second-phase treatment involves a full loading dose of IV fosphenytoin, levetiracetam, valproic acid, or phenobarbital 8

Administration Routes

Different administration routes are available for benzodiazepines, including:

• Intravenous
• Intramuscular
• Rectal
• Intranasal
• Intrapulmonary administration via an inhaler (investigated in recent years) 4