What is the recommended treatment approach for a patient with epilepsy, considering factors such as age, medical history, and potential pregnancy?

Epilepsy Treatment Approach

For most adults with newly diagnosed epilepsy, initiate monotherapy with levetiracetam 500 mg twice daily, titrating by 1000 mg/day every 2 weeks to a target of 3000 mg/day (1500 mg twice daily), as this provides optimal seizure control with minimal drug interactions and is safe across all patient populations including women of childbearing potential. 1, 2

Initial Monotherapy Selection

Levetiracetam is the preferred first-line agent for most patients with epilepsy due to its superior safety profile and lack of significant drug interactions. 1, 2, 3

• Start with 500 mg twice daily (1000 mg/day total) and increase by 1000 mg/day increments every 2 weeks until reaching the target dose of 3000 mg/day. 2
• The 3000 mg/day dose demonstrates optimal efficacy, with 68-73% seizure control rates in clinical trials. 1
• Levetiracetam can be taken with or without food, simplifying adherence. 2

Key Advantages of Levetiracetam

• No hepatic enzyme induction, eliminating concerns about drug interactions with oral contraceptives, warfarin, or other medications. 3
• Minimal protein binding and renal excretion, making dosing straightforward. 3
• Safe in pregnancy compared to valproate, which causes significant fetal malformations and neurodevelopmental delays. 1
• Available in IV formulation for acute situations or patients unable to take oral medications. 3

Age-Specific Dosing Considerations

Pediatric Patients (Ages 4-16 Years)

• Start with 20 mg/kg/day divided twice daily (10 mg/kg BID). 2
• Increase by 20 mg/kg increments every 2 weeks to the target dose of 60 mg/kg/day (30 mg/kg BID). 2
• Children ≤20 kg must use oral solution; those >20 kg can use tablets or solution. 2
• The mean effective dose in clinical trials was 52 mg/kg/day. 2

Older Adults

• Begin at standard adult dosing (500 mg BID) but monitor closely for somnolence and dizziness, which are more common in this population. 3
• Consider slower titration if tolerability issues emerge. 4

Women of Childbearing Potential and Pregnancy

Absolutely avoid valproate in women who could become pregnant, as it causes significantly increased risks of fetal malformations and neurodevelopmental delay. 1

• Levetiracetam is the safest antiepileptic option for women of childbearing age. 1
• Continue levetiracetam throughout pregnancy at the same dose that controls seizures, as uncontrolled seizures pose greater risk to mother and fetus than the medication. 1
• Maintain the effective dose rather than reducing it due to pregnancy concerns. 1

When Initial Monotherapy Fails

Optimizing the First Drug

Before adding a second medication, ensure the patient has reached maximum tolerated levetiracetam dose (3000 mg/day for adults, 60 mg/kg/day for children). 1, 2

• Check serum levetiracetam levels to assess compliance before assuming treatment failure. 1
• Investigate precipitating factors: sleep deprivation, alcohol use, medication non-compliance, and intercurrent illness can trigger breakthrough seizures even with adequate drug levels. 1
• Consider EEG monitoring to distinguish true epileptic seizures from psychogenic events or to detect subclinical seizure activity. 1, 5

Adding a Second Agent

If seizures persist despite optimized levetiracetam monotherapy, add valproate 20-30 mg/kg/day (avoiding in women of childbearing potential). 1

• Valproate and levetiracetam can be safely combined without significant pharmacokinetic interactions. 1
• This combination provides complementary mechanisms of action. 1
• Monitor liver function tests due to valproate's hepatotoxicity risk. 1

Alternative second agents include:

• Lamotrigine for patients requiring a safer profile in pregnancy. 1
• Lacosamide as another adjunctive option. 1

Critical Pitfall to Avoid

Never use phenytoin, carbamazepine, or phenobarbital as first-line agents due to significant drug interactions, side effects, and enzyme induction that complicates management of other medications. 1

Refractory Epilepsy (Failure of Two Adequate Medication Trials)

If two appropriately selected and dosed antiepileptic drugs fail to control seizures, refer immediately to an epilepsy center for surgical evaluation. 5

• Additional medications beyond two trials are unlikely to achieve seizure freedom. 5
• Epilepsy surgery renders 60-70% of patients with temporal lobe epilepsy free of disabling seizures, far exceeding medication success rates in refractory cases. 5
• Surgical options include resective surgery, corpus callosotomy, vagus nerve stimulation, and dietary interventions. 6

Acute Seizure Management

When to Activate Emergency Services

Call EMS immediately for: 7

• First-time seizure
• Seizure lasting >5 minutes
• Multiple seizures without return to baseline between episodes
• Seizures in water, with traumatic injury, difficulty breathing, or choking
• Seizure in infant <6 months or pregnant individual
• No return to baseline within 5-10 minutes after seizure stops

First Aid During Seizure

Protect the patient from injury: 7

• Help the person to the ground
• Place on their side in recovery position
• Clear the area around them
• Stay with the person continuously

Critical safety measures (Class 3 Harm recommendations): 7, 8

• Never restrain the seizing patient
• Never put anything in the patient's mouth
• Never give oral medications, food, or liquids during or immediately after seizure

Status Epilepticus (Seizures >5 Minutes)

Administer IV lorazepam 4 mg at 2 mg/min immediately (or 0.1 mg/kg in pediatrics, max 2 mg per dose). 1, 9

If seizures continue after two doses of lorazepam, immediately give one of the following second-line agents: 1, 9

• Levetiracetam 30 mg/kg IV over 5 minutes (68-73% efficacy, minimal cardiovascular effects)
• Valproate 20-30 mg/kg IV over 5-20 minutes (88% efficacy, 0% hypotension risk)
• Fosphenytoin 20 mg PE/kg IV at max 50 mg/min (84% efficacy, but 12% hypotension risk requiring cardiac monitoring)

Special Considerations for Febrile Seizures in Children

Do not administer antipyretics (acetaminophen, ibuprofen) to stop or prevent febrile seizures, as they are ineffective for this purpose. 7

• Febrile seizures affect 2-4% of children, most commonly between 6 months and 2 years of age. 7
• These are typically benign and self-limited. 7
• Focus on supportive care and positioning rather than fever reduction. 7

Monitoring and Follow-Up

Question the patient about seizure occurrences at every follow-up visit to assess treatment efficacy. 1

• Goal of therapy: complete seizure freedom on a single drug taken once or twice daily without adverse effects. 4
• If control is difficult, explore maximum tolerated dose while balancing adverse effects against seizure control. 4
• Up to 70% of patients can expect seizure freedom with optimized antiepileptic drug therapy. 4