Levetiracetam (Keppra) for Seizure Prophylaxis in Brain Injury
Levetiracetam is recommended for seizure prophylaxis only during the first 7 days after traumatic brain injury, with a typical dose of 1000-1500 mg per day. 1, 2
Indications and Efficacy
- Prophylactic antiepileptic drugs are recommended only during the first seven days after traumatic brain injury according to the Brain Trauma Foundation and American Academy of Neurology guidelines 2
- Levetiracetam has demonstrated comparable efficacy to phenytoin for early post-traumatic seizure prophylaxis and may be a reasonable alternative with fewer adverse effects and monitoring considerations 2
- Routine seizure prophylaxis beyond 7 days post-injury is not recommended due to lack of evidence supporting its benefit 1, 2
Dosing Recommendations
- For seizure prophylaxis in traumatic brain injury, levetiracetam can be administered at 1000-1500 mg per day 3
- For active seizure treatment, a loading dose of 1500 mg orally or intravenously is recommended 1
- For patients with status epilepticus, higher doses of up to 30 mg/kg IV at a rate of 5 mg/kg per minute may be considered 4
- Lower doses (≤1000 mg/day) have shown similar or potentially better efficacy compared to higher doses in some studies, though differences were not statistically significant 3
Duration of Treatment
- Prophylactic treatment should be limited to 7 days post-injury 1, 2
- Continuing levetiracetam beyond 7 days in patients without seizures is not supported by evidence and is considered inappropriate use 5
- Studies have shown that 23.3% of patients with non-severe TBI inappropriately receive levetiracetam for more than seven days 5
Special Considerations
- Patients with CAR T-cell therapy who have CNS disease or history of seizures should receive levetiracetam prophylaxis (10 mg/kg, maximum 500 mg per dose) every 12 hours for 30 days following infusion 1
- For post-cardiac arrest seizures, levetiracetam is considered a first-line treatment option along with valproate, as these drugs have fewer adverse effects compared to fosphenytoin 1
- Routine seizure prophylaxis is not recommended in post-cardiac arrest patients due to lack of evidence showing benefit 1
Monitoring and Adverse Effects
- Unlike phenytoin, levetiracetam does not require therapeutic drug monitoring or have significant pharmacokinetic interactions 6, 2
- Common adverse effects include fatigue, dizziness, and rarely pain at infusion site 1
- Some studies have reported an increased seizure tendency on EEG with levetiracetam compared to phenytoin, despite similar clinical seizure rates 6
- Dose adjustments may be necessary in patients with renal dysfunction 1
Efficacy Comparison with Other Agents
- Levetiracetam has shown comparable efficacy to phenytoin in preventing early post-traumatic seizures 2
- In status epilepticus, levetiracetam has demonstrated a response rate of 67-73% 4
- In elderly patients with documented status epilepticus, levetiracetam 1,500 mg has shown 89% reduction in seizures and 78% complete cessation 4
- For treatment of post-cardiac arrest seizures, levetiracetam and valproate are preferred over fosphenytoin due to lower rates of hypotension and need for intubation 1
Controversies and Limitations
- One propensity score-matched cohort analysis found levetiracetam prophylaxis ineffective in preventing seizures in TBI patients 7
- The overall incidence of post-traumatic seizures in severe TBI patients was only 2.0% in some studies, raising questions about the benefit of routine prophylactic therapy 7
- Inappropriate use of levetiracetam is common in patients with non-severe TBI (GCS > 8), with many patients continuing treatment post-discharge without clear indication 5
Remember that seizure treatment is distinct from seizure prophylaxis, with treatment being indicated for active seizures regardless of the timeframe, while prophylaxis is generally only recommended for the first 7 days after brain injury.