What is the best course of action for a patient with a history of seizures after head trauma, now experiencing exacerbation due to non-compliance with antiepileptic medication (AED) therapy?

Management of Post-Traumatic Seizures with Medication Non-Compliance

Restart the patient's antiepileptic medication immediately at appropriate loading and maintenance doses, as medication non-compliance is the primary cause of breakthrough seizures in patients with established post-traumatic epilepsy. 1

Immediate Assessment and Intervention

Confirm the Clinical Scenario

• This patient has established post-traumatic epilepsy (remote symptomatic seizures from prior head trauma), not acute traumatic brain injury requiring prophylaxis 1
• The current seizure exacerbation is provoked by medication non-compliance, making this a treatable and reversible cause 1, 2
• Non-compliance affects one-third to one-half of epilepsy patients and is the single most important factor in breakthrough seizures 3

Acute Seizure Management (If Actively Seizing)

• Administer IV lorazepam 4 mg at 2 mg/min as first-line treatment if the patient is actively seizing, with 65% efficacy in terminating seizures 4
• For refractory seizures after benzodiazepines, use levetiracetam 30 mg/kg IV over 5 minutes (68-73% efficacy with minimal cardiovascular effects) or valproate 20-30 mg/kg IV over 5-20 minutes (88% efficacy) 4, 5
• Avoid phenytoin/fosphenytoin as second-line unless other agents are unavailable, given only 56% efficacy and 12% hypotension risk 4, 5

Restarting Maintenance Antiepileptic Therapy

Medication Selection Priority

Choose based on the patient's previous medication regimen if it was effective before non-compliance: 1, 5

• Levetiracetam: Load with 1,500 mg orally or up to 60 mg/kg IV, then maintain at 500-1,500 mg twice daily; offers the best safety profile with minimal drug interactions and only 0.7% risk of life-threatening hypotension 1, 4, 5

• Valproate: Load with 20-30 mg/kg IV (up to 30 mg/kg), then maintain at 10-15 mg/kg/day initially, increasing by 5-10 mg/kg/week to achieve 50-100 μg/mL therapeutic levels; contraindicated in liver disease and women of childbearing potential 6, 5

• Phenytoin: Load with 20 mg/kg divided in maximum 400 mg doses every 2 hours orally (takes >5 hours to reach therapeutic levels) or 18 mg/kg IV at maximum 50 mg/min; requires cardiac monitoring and filter/infusion pump for IV administration 1

• Carbamazepine: Start at 200 mg twice daily, increase weekly by 200 mg/day to usual maintenance of 800-1,200 mg daily; requires gradual titration and has significant drug interactions 7, 8

Loading Strategy

For patients with known epilepsy and breakthrough seizures from non-compliance, immediate loading is appropriate: 1, 5

• Oral loading is acceptable if the patient is not actively seizing and can tolerate oral intake 1
• IV loading is preferred if the patient has altered mental status, is actively seizing, or cannot take oral medications 1, 4
• There is no significant difference in seizure recurrence between oral and IV loading in patients who have returned to baseline 1

Addressing Non-Compliance

Identify Barriers to Compliance

Non-compliance is multidimensional and requires individualized assessment: 3

• Measure antiepileptic drug levels to confirm non-compliance (coefficient of variation for serial levels may be more descriptive) 3
• Use both pill-count and structured questionnaires (e.g., Morisky scale), as single tools miss up to 20% of non-compliant patients 2
• Interview the patient to identify specific barriers: cost, side effects, dosing complexity, forgetfulness, or intentional discontinuation 3

Strategies to Improve Compliance

Simplify the medication regimen: 8, 3

• Prescribe once or twice daily dosing whenever possible to improve adherence 8
• Use monotherapy rather than combination therapy to reduce adverse effects, drug interactions, and complexity 8
• Provide education about the consequences of non-compliance, including breakthrough seizures, emergency visits, injuries, and increased mortality 2
• Consider dosing devices or pill organizers to address forgetfulness 3

Disposition and Follow-Up

Emergency Department Discharge Criteria

Patients who have returned to clinical baseline after a breakthrough seizure from non-compliance do not require admission: 1

• Ensure the patient has resumed therapeutic antiepileptic medication before discharge 1
• Provide clear instructions for continued medication adherence 1
• Arrange close outpatient neurology follow-up within 1-2 weeks 1

Admission Indications

Admit patients who: 1

• Have not returned to baseline mental status after seizure 1
• Continue to have seizures despite appropriate treatment 1
• Have concerning findings on neuroimaging suggesting new pathology 1
• Lack reliable social support to ensure medication compliance 1

Critical Pitfalls to Avoid

• Do not assume the seizure is from new pathology without first confirming medication non-compliance through drug levels and patient interview 1, 3
• Do not use antiepileptic drugs for primary prevention in acute traumatic brain injury, as this patient has established epilepsy, not acute TBI requiring prophylaxis 1
• Do not abruptly discontinue antiepileptic drugs once restarted, as this precipitates status epilepticus with attendant hypoxia and life-threatening complications 6, 7
• Do not prescribe complex multi-drug regimens without first optimizing monotherapy, as this worsens compliance 8
• Do not discharge without ensuring the patient has medication in hand and understands the dosing schedule 3