How to stop nighttime seizures on Lamictal (lamotrigine) and Depakote (valproate)?

Managing Nighttime Seizures with Lamotrigine and Valproate

For patients experiencing nighttime seizures while on lamotrigine (Lamictal) and valproate (Depakote), adding levetiracetam as a third agent is recommended due to its favorable efficacy and side effect profile for refractory seizures. 1

Evaluation of Current Therapy

Before adding a third medication, consider the following:

• Dosage optimization: Ensure current medications are at therapeutic levels

  • Lamotrigine (250mg): Therapeutic range is typically 3-14 μg/mL
  • Valproate (1000mg): Therapeutic range is typically 50-100 μg/mL

• Timing adjustment: Consider shifting more of the valproate dose to evening to improve nighttime seizure control

• Adherence assessment: Confirm consistent medication intake, as missed doses can trigger breakthrough seizures

Adding a Third Agent

If seizures persist despite optimized doses of lamotrigine and valproate, adding a third agent is appropriate:

Preferred Option: Levetiracetam

• Starting dose: 500mg at bedtime
• Titration: Increase by 500mg every 1-2 weeks as needed
• Target dose: 1000-2000mg daily (with higher proportion in evening)
• Advantages:
  • Minimal drug interactions with current regimen 1
  • Favorable side effect profile
  • No hepatic metabolism (important when combined with valproate) 1
  • 44-73% efficacy rate in refractory seizures 1

Alternative Options:

1. Zonisamide:

   • Consider if levetiracetam is not tolerated
   • However, research shows lamotrigine is superior to zonisamide for seizure control 2

2. Ethosuximide:

   • May be beneficial as an add-on specifically if absence seizures are present 3
   • Particularly effective when combined with valproate 4

Lifestyle Modifications

In addition to medication adjustments:

• Sleep hygiene: Establish consistent sleep schedule
• Avoid triggers: Minimize alcohol, caffeine, and sleep deprivation
• Safety measures: Consider using bed alarms or monitoring devices for nighttime seizures
• Positioning: Sleep in recovery position (on side) to prevent airway complications during seizures

Monitoring Plan

• EEG monitoring: Consider overnight EEG to characterize seizures, especially if mental status changes occur 5
• Laboratory monitoring:
  • Baseline CBC, LFTs, valproate level, renal function, electrolytes
  • Regular monitoring of drug levels every 3 months
  • More frequent monitoring during medication adjustments 1

Important Considerations

• Avoid prophylactic anticonvulsants without clear evidence of seizures 5
• Women of childbearing potential: Note that valproate carries significant teratogenicity risks; levetiracetam is preferred in this population 1
• Medication interactions: Monitor closely as you're on multiple antiepileptic drugs
• Adverse effects to watch for:
  • Lamotrigine: Rash (potentially serious), dizziness, headache
  • Valproate: Gastrointestinal disturbances, tremor, weight gain, hair loss
  • Levetiracetam: Irritability, mood changes, somnolence 1

If seizures remain uncontrolled despite these interventions, referral to a comprehensive epilepsy center for video-EEG monitoring and consideration of surgical options may be warranted.