What is the management of epilepsy?

Management of Epilepsy

The first-line treatment for active seizures is benzodiazepines, followed by levetiracetam, valproate, or phenytoin as equally effective second-line options if seizures persist, with the choice depending on patient-specific factors such as comorbidities and potential side effects. 1

Definition and Classification

Epilepsy is a common neurological disorder affecting 1-3% of the population, characterized by recurrent unprovoked seizures 2. Status epilepticus is defined as seizures lasting more than 5 minutes or multiple seizures without return to baseline, requiring emergency intervention 1.

Initial Management of Active Seizures

First-Line Treatment

• Benzodiazepines are the first-line treatment for active seizures 1
• For status epilepticus, IV lorazepam is preferred over diazepam if available 1

Second-Line Treatment (if seizures persist)

• Valproate: 20-40 mg/kg IV (maximum rate 6 mg/kg/min)

  • Particularly effective with less hypotension than phenytoin 1
  • In studies comparing valproate to phenytoin, valproate showed better seizure control (79% vs 25%) 3
  • No association with hypotension, unlike phenytoin (12% hypotension rate) 3

• Levetiracetam: 30 mg/kg IV

  • Similar efficacy to valproate 1
  • Preferred in patients with hepatic dysfunction 1

• Phenytoin/Fosphenytoin: 18 mg/kg

  • Traditional second-line agent 3
  • Less effective than valproate in some studies (56% success rate) 3
  • Associated with higher risk of hypotension 3

Treatment Selection Algorithm

1. For focal seizures:

   • First choice: Lamotrigine or levetiracetam 4
   • Alternative: Carbamazepine or oxcarbazepine 4
   • Avoid levetiracetam in patients with psychiatric disorders 5

2. For generalized seizures:

   • First choice: Sodium valproate (unless contraindicated) 4
   • Alternatives: Lamotrigine or levetiracetam (especially for women of childbearing potential) 4
   • Avoid valproate in women of childbearing potential due to teratogenic effects 6

3. For status epilepticus:

   • First: Benzodiazepines (IV lorazepam preferred) 1
   • Second: Valproate, levetiracetam, or phenytoin 3, 1
   • For refractory cases: Consider ICU transfer with continuous EEG monitoring and anesthetic agents 1

Medication-Specific Considerations

Valproate

• Efficacy: Effective for both focal and generalized seizures 4
• Caution: Hepatotoxicity risk, especially in first 6 months of treatment 6
• Monitoring: Liver function tests before therapy and at frequent intervals 6
• Contraindications: Pregnancy (teratogenic effects), hepatic disease 6

Phenytoin

• Pharmacokinetics: Plasma half-life averages 22 hours (range 7-42 hours) 7
• Therapeutic levels: 10-20 mcg/mL 7
• Caution: Highly protein-bound; levels may be altered in patients with different protein binding characteristics 7
• Monitoring: Serum levels should be obtained at least 5-7 half-lives after treatment initiation 7

Levetiracetam

• Advantages: Less variable kinetics, lower interaction potential 8
• Primary use: Effective in partial seizures 8
• Caution: May exacerbate psychiatric symptoms 5

Carbamazepine

• Cautions:
  • May increase isoniazid-induced hepatotoxicity 9
  • Can render hormonal contraceptives less effective 9
  • May cause resistance to neuromuscular blocking agents 9
  • Decreases effectiveness of direct oral anticoagulants 9

Diagnostic Workup for New-Onset Seizures

Essential Laboratory Tests

• Serum glucose and sodium for all patients
• Pregnancy test for women of childbearing age
• Complete metabolic panel for altered mental status
• Toxicology screen if substance use suspected
• CBC, blood cultures, lumbar puncture if fever present
• Antiepileptic drug levels for patients on seizure medications 1

Imaging

• MRI is preferred over CT for detecting brain abnormalities 1
• EEG should be performed within 24-48 hours of first-time seizures 1

Discharge Criteria and Follow-up

Patients can be discharged if they:

• Have returned to baseline mental status
• Had a single self-limited seizure with no recurrence
• Have normal or non-acute findings on neuroimaging
• Have reliable follow-up available
• Have a responsible adult to observe them 1

Common Pitfalls and Caveats

1. Medication selection: Avoid valproate in women of childbearing potential due to teratogenic effects 6

2. Monitoring: Don't rely solely on serum biochemistry for hepatotoxicity monitoring with valproate; clinical symptoms may precede abnormal tests 6

3. Drug interactions: Be aware that enzyme-inducing AEDs (carbamazepine, phenytoin) can affect metabolism of other medications and worsen comorbid conditions 5

4. Treatment failure: If trials of more than two AEDs fail to control seizures, refer to an epilepsy center for consideration of surgical options 2

5. Status epilepticus management: Don't delay treatment; mortality increases significantly in cases refractory to first-line therapies 1

6. Phenytoin dosing: Small incremental doses may disproportionately increase serum levels when these are in the upper range, potentially causing toxicity 7