What is the role of anti-epileptics (AEDs) in a patient with hypertensive intracerebral hemorrhage (ICH)?

Antiepileptic Drugs in Intracerebral Hemorrhage

Prophylactic antiepileptic drugs should NOT be routinely administered to patients with intracerebral hemorrhage, as they do not prevent seizures and are associated with worse functional outcomes including increased death and disability. 1, 2

When to Withhold Antiepileptic Drugs

Do not use prophylactic antiepileptic drugs in ICH patients without documented seizures. The evidence is clear on this point:

• Meta-analyses demonstrate that seizure prophylaxis does not prevent early or late seizures in ICH patients 2, 3
• Prophylactic AED use is independently associated with increased odds of death or severe disability at 90 days (OR 6.8; 95% CI: 2.2-21.2), even after adjusting for ICH volume, age, GCS, and other outcome predictors 4
• Phenytoin specifically is associated with significantly worse outcomes and should be avoided entirely 1, 2
• Clinical seizures have not been associated with worsened neurologic outcome or mortality in prospective studies 1

When to Treat with Antiepileptic Drugs

Initiate antiepileptic drugs ONLY when:

• Clinical seizures are documented 1, 2
• Electrographic seizures are detected on EEG AND contribute to impaired consciousness or altered mental status 1, 2

This is a critical distinction—treat documented seizures, not the theoretical risk of seizures.

EEG Monitoring Indications

Obtain continuous EEG monitoring for at least 24-48 hours when:

• Depressed mental status is out of proportion to the degree of brain injury 1, 2
• Fluctuating level of consciousness cannot be explained by metabolic abnormalities 2
• Clinical seizures are suspected 2

The rationale: 28-31% of select ICH cohorts have electrographic seizures on continuous EEG, with 28% detected after 24 hours and 94% by 48 hours 1, 2, 5

Medication Selection When Treatment is Required

If seizures are documented and require treatment, use levetiracetam as first-line therapy:

• Levetiracetam is preferred over phenytoin/fosphenytoin due to better tolerability and fewer adverse effects 2, 5
• Avoid phenytoin and fosphenytoin entirely—they are associated with increased death and disability in ICH patients 1, 2
• Phenytoin may also dampen neural plasticity mechanisms that contribute to behavioral recovery after stroke 1

Duration of Treatment

Do not continue prophylactic antiepileptic medications beyond the acute treatment period unless recurrent seizures occur:

• Risk scores should not be used to justify continuation of prophylactic AEDs beyond 7 days, as there is no evidence they prevent late seizures 2
• Treat documented seizures only—discontinue AEDs once the acute seizure activity is controlled if no recurrent seizures occur 2

Common Pitfalls to Avoid

Critical errors to prevent:

• Do not prescribe AEDs "just in case" for lobar ICH or cortical involvement—while cortical involvement increases seizure risk, prophylaxis still does not improve outcomes and may worsen them 1, 2, 5
• Do not assume early seizures worsen outcomes—prospective studies show early seizures are not independently associated with worse neurological outcomes or mortality 1, 2
• Do not use phenytoin under any circumstances in ICH patients—the evidence for harm is robust 1, 2, 4
• Do not continue AEDs started in the emergency department or ICU without documented seizures—reassess and discontinue if no seizures occurred 2, 4

Addressing Contradictory Evidence

One retrospective study suggested levetiracetam prophylaxis reduced seizure events (adjusted OR 0.28) 6, but this contradicts multiple guidelines and meta-analyses showing no benefit 2, 3. The guideline-level evidence from the American Heart Association/American Stroke Association is more robust and should take precedence, particularly given the consistent finding across multiple studies that prophylactic AED use is associated with worse functional outcomes 1, 2, 4.