Seizure Prophylaxis in Traumatic Brain Injury
Primary Recommendation
Routine prophylactic antiepileptic drugs (AEDs) are not recommended for all TBI patients, but when indicated for high-risk cases, use levetiracetam 500-1000mg twice daily for 7 days maximum, as it offers better tolerability than phenytoin without proven superiority in seizure prevention. 1, 2
When to Consider Prophylaxis (Not Routinely Recommended)
The evidence does not support routine seizure prophylaxis in TBI. 1, 2 Analysis of 11 clinical trials involving over 2,700 patients showed no significant effect of AEDs in preventing early or delayed post-traumatic seizures, and some studies demonstrated worsening neurological outcomes with prophylaxis. 2
However, prophylaxis may be considered in specific high-risk scenarios:
- Chronic subdural hematoma 1
- Past history of epilepsy 1
- Acute subdural hematoma (though this alone does not justify routine prophylaxis) 2
- Initial loss of consciousness or amnesia >24 hours 2
Drug Selection: Levetiracetam Over Phenytoin
If prophylaxis is deemed necessary, levetiracetam should be preferred over phenytoin due to superior tolerability. 1, 3
Advantages of Levetiracetam:
- Better tolerability profile with fewer adverse effects 3, 4
- No therapeutic drug monitoring required 4
- No significant drug-drug interactions 4
- Does not induce fever or alter drug metabolism like phenytoin 5
Critical Caveat About Levetiracetam:
- Levetiracetam is associated with increased seizure tendency on EEG analysis despite preventing clinical seizures as effectively as phenytoin 4, 5
- One propensity-matched study found levetiracetam prophylaxis ineffective, showing no difference in seizure rates (1.9% vs 3.4%, p=0.50) compared to no prophylaxis 6
- However, a military cohort study showed low seizure incidence (2.8%) with levetiracetam prophylaxis 7
Duration of Prophylaxis: 7 Days Maximum
Prophylactic AEDs should not be continued beyond 7 days after injury. 3, 2, 4
- Seven-day prophylaxis is as effective as 21-day prophylaxis for preventing seizures (8.9% vs 11.1%, p=0.725), with longer duration associated with more adverse effects 8
- The American Heart Association recommends against long-term continuation unless specific risk factors for delayed seizures are present 3
- Do not continue prophylactic antiepileptics long-term unless actual seizures occur 2
Phenytoin Should Be Avoided When Possible
Phenytoin is associated with excess morbidity and mortality in subdural hematoma patients and should be avoided. 3
- Phenytoin alters drug metabolism, induces fever, and requires therapeutic monitoring 5
- Valproate demonstrates similar efficacy to phenytoin but is associated with increased mortality 4
- Phenobarbital and carbamazepine offer no advantage over phenytoin and have worse adverse-effect profiles 4
Monitoring Considerations
Continuous EEG monitoring should be considered in patients with depressed mental status disproportionate to their brain injury to detect subtle seizure activity. 3, 9
- Early post-traumatic seizures occur in approximately 2.2% of all TBI cases but up to 38% in acute subdural hematoma 3
- Serial neurological examinations are essential for post-surgical management 3
Key Clinical Pitfalls
- Avoid polypharmacy when monotherapy would suffice 2
- Prophylactic AEDs may worsen cognitive outcomes in subdural hematoma patients, emphasizing the need to weigh risks versus benefits 3
- The overall incidence of post-traumatic seizures in severe TBI is only 2.0%, questioning the benefit of routine prophylaxis 6
- If seizures occur despite levetiracetam therapy, consider alternative second-line agents like fosphenytoin for breakthrough seizures 2