What are the initial treatment options for seizures, including first-line antiepileptic drugs (AEDs)?

Initial Treatment for Seizures

For acute seizures or status epilepticus, immediately administer IV benzodiazepines (lorazepam preferred), followed by valproate or levetiracetam as second-line agents if seizures persist; for chronic epilepsy management, carbamazepine or lamotrigine are first-line for focal seizures, while valproate is first-line for generalized seizures. 1, 2

Acute Seizure Management (Status Epilepticus)

First-Line Treatment: Benzodiazepines

• Administer IV benzodiazepines immediately for any seizure lasting >5 minutes or consecutive seizures without recovery of consciousness 2
• Lorazepam is the preferred benzodiazepine due to its longer duration of action compared to diazepam 1, 2
• If IV access is unavailable, use rectal diazepam; IM diazepam is not recommended due to erratic absorption 1
• IM phenobarbital may be considered when rectal diazepam is not feasible for medical or social reasons 1

Second-Line Treatment for Refractory Seizures

If seizures persist after benzodiazepines, immediately administer one of the following agents 1, 2:

Valproate (Preferred Second-Line Agent)

• Dose: 30 mg/kg IV at 6 mg/kg/hour, followed by maintenance infusion of 1-2 mg/kg/hour 1, 2, 3
• Achieves 88% seizure control within 20 minutes and 79% control as second-line agent versus 25% with phenytoin 4, 2
• Superior safety profile with no hypotension reported versus 12% with phenytoin 3
• Critical contraindications: women of childbearing potential (teratogenic risk) and young children (hepatotoxicity risk) 4, 2

Levetiracetam (Alternative Second-Line Agent)

• Dose: 30 mg/kg IV at 5 mg/kg per minute 4, 2, 3
• Demonstrates 73% response rate in refractory status epilepticus 4, 2
• Similar efficacy to valproate (47% vs 46% cessation at 60 minutes) 4
• Minimal drug interactions and favorable safety profile, particularly useful in hepatic dysfunction 3

Phenytoin/Fosphenytoin (Traditional Option)

• Dose: 18-20 mg/kg IV at 50 mg per minute 1, 2
• Lower efficacy (56% termination rate after benzodiazepines) compared to valproate and levetiracetam 1, 3
• Higher risk of hypotension (12% of patients) and cardiac dysrhythmias 1, 3
• Consider only when valproate and levetiracetam are contraindicated 3

Third-Line Treatment for Persistent Seizures

• Propofol is preferred over barbiturates: 2 mg/kg bolus followed by 5 mg/kg/hour infusion 1, 2
• Propofol requires fewer mechanical ventilation days (4 days) compared to pentobarbital (14 days) 1, 2
• Barbiturates (phenobarbital/pentobarbital) have fallen out of favor due to significant respiratory depression and hypotension 1, 2

Chronic Epilepsy Management

For Focal Onset Seizures

Carbamazepine or lamotrigine are first-line treatments, with levetiracetam as an excellent alternative 1, 4, 5:

• Lamotrigine performs better than most other treatments in terms of treatment failure for any reason and adverse events 5
• Carbamazepine is preferentially offered to children and adults with partial onset seizures when available 1, 4
• Levetiracetam represents an effective alternative with excellent tolerability for pediatric patients 4
• No significant difference exists between lamotrigine and levetiracetam for treatment failure outcomes 5

For Generalized Tonic-Clonic Seizures

Valproate is the first-line treatment, but lamotrigine or levetiracetam are suitable alternatives 1, 5:

• Valproate demonstrates superior efficacy compared to all other treatments for generalized seizures 5
• Avoid valproate in women of childbearing potential due to teratogenic risk 4, 2
• Lamotrigine and levetiracetam show no significant differences compared to valproate in treatment failure rates 5
• Phenobarbital may be offered as first option in resource-limited settings if availability can be assured 1

Critical Treatment Principles

Monotherapy First

• Always use monotherapy with a single antiepileptic drug at the minimum effective dose 1, 4
• Never use polytherapy when monotherapy can achieve seizure control to minimize adverse effects and drug interactions 4
• If first monotherapy fails, switch to alternative monotherapy before considering combination therapy 6, 7

When NOT to Treat

• Do not routinely prescribe antiepileptic drugs after a first unprovoked seizure 1, 4
• Treatment may be considered after first seizure only in patients with abnormal EEG and imaging findings or severe social/emotional implications 7
• Do not use prophylactic anticonvulsants in patients with no seizure history 4

Treatment Discontinuation

• Consider discontinuation after 2 seizure-free years, involving the patient and family in the decision 1, 4
• Base the decision on clinical, social, and personal factors rather than arbitrary timelines 1

Age-Specific Considerations

Pediatric Patients

• Carbamazepine is preferred for children with partial onset seizures 1, 4
• Avoid valproic acid in young children due to significant hepatotoxicity risk 4
• Phenobarbital may be considered for infants but carries substantial risk of behavioral adverse effects 4
• Levetiracetam dosing: 30-40 mg/kg for acute treatment 3

Women of Childbearing Potential

• Avoid valproic acid due to teratogenic risk; use carbamazepine or lamotrigine instead 4, 2
• Maintain seizure control with monotherapy at minimum effective dose 1
• Routinely prescribe folic acid supplementation when on antiepileptic drugs 1

Common Pitfalls to Avoid

• Delaying second-line treatment after benzodiazepines increases morbidity and mortality 2
• Using IM diazepam (erratic absorption makes it ineffective) 1
• Prescribing phenytoin in hemodynamically unstable patients (risk of hypotension) 1, 3
• Starting polytherapy before optimizing monotherapy 4, 6
• Failing to search for treatable causes (hypoglycemia, hyponatremia, hypoxia, drug toxicity, infection) during acute seizure management 2