What is the treatment for epilepsy and seizures?

Epilepsy vs Seizure: Treatment Approach

A single unprovoked seizure does not require antiepileptic drug (AED) treatment, but epilepsy—defined as two or more unprovoked seizures—requires chronic AED therapy, with treatment selection based on seizure type and epilepsy syndrome. 1, 2

Key Distinction Between Seizure and Epilepsy

• A seizure is a single event—a symptom that can occur from acute provoked causes (hypoglycemia, drug toxicity, alcohol withdrawal, electrolyte imbalance) or as an unprovoked event 3, 4
• Epilepsy is a chronic disorder characterized by recurrent unprovoked seizures, affecting 1-3% of the population and requiring ongoing treatment 3
• Provoked seizures are treated by correcting the underlying cause (e.g., correcting hypoglycemia, treating infection, managing drug toxicity) without initiating AEDs 1, 4

When to Start Treatment After a First Seizure

Do NOT start AEDs after a first unprovoked seizure unless high-risk factors are present, as delaying therapy until a second seizure does not affect long-term remission rates 1, 2

High-Risk Factors That Warrant Treatment After First Seizure:

• Two unprovoked seizures occurring more than 24 hours apart 2
• Epileptiform abnormalities on EEG 1, 2
• Abnormal brain imaging showing structural lesion 1, 3
• History of prior brain insult 3
• Nocturnal seizures 2
• Identified epileptic syndrome 2

In children specifically, additional risk factors include severe head trauma and cerebral palsy 2

Treatment for Established Epilepsy (≥2 Unprovoked Seizures)

First-Line Monotherapy Selection by Seizure Type:

For Partial Onset Seizures:

• Carbamazepine should be preferentially offered to children and adults with partial onset seizures, particularly in resource-limited settings 1
• Levetiracetam is effective as adjunctive therapy for partial onset seizures in adults and children ≥4 years, starting at 20 mg/kg/day in children or 1000 mg/day in adults 5
• Phenobarbital is acceptable if cost is a constraint and availability can be assured 1

For Generalized Tonic-Clonic Seizures:

• Valproic acid is the preferred agent for generalized seizures, along with lamotrigine and topiramate 3
• Levetiracetam is indicated for primary generalized tonic-clonic seizures in adults and children ≥6 years at 60 mg/kg/day (maximum 3000 mg/day) 5
• Topiramate is indicated as monotherapy for primary generalized tonic-clonic seizures in patients ≥10 years 6

For Myoclonic Seizures:

• Levetiracetam is indicated for juvenile myoclonic epilepsy in patients ≥12 years at 3000 mg/day 5

Critical Treatment Principles:

• Start with monotherapy—using one AED at a time is the standard approach 1, 3
• Avoid valproic acid in women of childbearing potential due to significant teratogenic risk 7
• Avoid enzyme-inducing anticonvulsants (phenytoin, carbamazepine, phenobarbital) when possible due to drug interactions and side-effect profiles 7
• Do NOT routinely monitor drug levels—this is not correlated with improved outcomes or reduced adverse effects 2

When to Consider Discontinuation

After 2 seizure-free years, discontinuation of AEDs should be considered with involvement of the patient and family, weighing clinical, social, and personal factors 1

After 2-5 seizure-free years, discontinuation may be appropriate in selected patients 2

Refractory Epilepsy Management

If trials of more than two AEDs fail to control seizures, refer to an epilepsy center for surgical evaluation, as epilepsy surgery renders 60-70% of temporal lobe epilepsy patients seizure-free 3

Status Epilepticus: Acute Seizure Emergency

For actively seizing patients, immediate treatment differs completely from chronic epilepsy management:

• First-line: IV lorazepam 4 mg at 2 mg/min (65% efficacy) 8
• Second-line options if seizures continue:
  • Valproate 20-30 mg/kg IV (88% efficacy, 0% hypotension risk) 8, 9
  • Levetiracetam 30 mg/kg IV (68-73% efficacy, minimal cardiovascular effects) 8, 9
  • Fosphenytoin 20 mg PE/kg IV (84% efficacy, but 12% hypotension risk requiring cardiac monitoring) 8, 9
• For refractory status epilepticus: Midazolam infusion (80% efficacy), propofol, or pentobarbital (92% efficacy) 8, 9

Critical Pitfall to Avoid:

Phenytoin is ineffective for seizures secondary to alcohol withdrawal, theophylline toxicity, or isoniazid toxicity—benzodiazepines remain first-line, and pyridoxine should be given if isoniazid poisoning is possible 10, 4

Common Pitfalls in Management

• Do NOT prescribe AEDs routinely after a first unprovoked seizure unless high-risk factors are present 1
• Do NOT use phenytoin for drug-induced seizures—it is ineffective in this context 10
• Do NOT continue AED therapy indefinitely without reassessing—most patients with provoked seizures do not have epilepsy and should not be labeled as such 4
• Do NOT use valproate in women who may become pregnant without careful counseling about teratogenic risks 7