Is there evidence for using antiseizure medications, such as levetiracetam (Keppra) or phenytoin (Dilantin), in patients with traumatic brain injury (TBI) and no history of seizures?

From the Guidelines

There is no evidence to support the routine use of antiseizure medications in patients with traumatic brain injury and no history of seizures, as prevention of post-traumatic seizures with antiepileptic drugs cannot be recommended 1. The current evidence suggests that the use of antiepileptic drugs for primary prevention to reduce the incidence of post-traumatic seizures is not recommended, with a strong agreement and a grade of 2- 1.

Key Points to Consider

• The incidence of early clinical seizures within 7 days after the brain injury is relatively low, at 2.2%, and the incidence of delayed seizures after 7 days is also 2.1% 1.
• Risk factors for delayed clinical seizures include brain contusion, acute subdural hematoma, skull fracture, initial loss of consciousness or amnesia for more than 24 hours, and age over 65 years 1.
• Eleven clinical trials have studied primary prevention of post-traumatic seizures, but all had a low level of evidence, and no significant effect of antiepileptic drugs was found to prevent the occurrence of early or delayed post-traumatic seizures 1.
• The use of antiepileptic drugs may be considered in cases with risk factors, such as chronic subdural hematoma, or past history of epilepsy, and levetiracetam should be preferred to phenytoin due to its higher degree of tolerance 1.

Clinical Implications

• The routine use of antiseizure medications in patients with traumatic brain injury and no history of seizures is not supported by the current evidence.
• Clinicians should carefully assess the individual patient's risk factors and consider the potential benefits and harms of antiepileptic drug use on a case-by-case basis.
• If antiepileptic drugs are used, levetiracetam may be preferred over phenytoin due to its more favorable side effect profile and lack of need for serum level monitoring 1.

From the Research

Evidence for Antiseizure Medications in Traumatic Brain Injury

• There is evidence to suggest that antiseizure medications, such as levetiracetam and phenytoin, may be used for seizure prophylaxis in patients with traumatic brain injury (TBI) and no history of seizures 2, 3, 4, 5, 6.
• A study published in 2019 found that phenytoin reaches therapeutic levels in cerebrospinal fluid (CSF) quickly, but levetiracetam does not reach therapeutic levels in CSF when loaded at standard dosing regimens in the acute setting 2.
• A clinical practice guideline published in 2024 suggests that antiseizure medications may be used in patients with moderate-severe TBI and no history of clinical or electrographic seizures, but the quality of evidence is low 3.
• Another study published in 2016 found that a lower dose of levetiracetam (500 mg every 12 hours) may be effective for early seizure prevention after TBI 4.
• A retrospective cohort study published in 2023 found that levetiracetam appears to be a safe and effective medication for post-traumatic seizure prophylaxis in combat casualties 5.
• A randomized controlled trial published in 2018 found that the incidence of abnormal EEGs and seizure activity in patients with TBI is the same for both levetiracetam and phenytoin for the initial 7 days post-TBI, but the incidence of seizures is lower for patients who used levetiracetam on subsequent follow-up 6.

Comparison of Levetiracetam and Phenytoin

• Some studies suggest that levetiracetam may be preferred over phenytoin due to its better side effect profile and lower incidence of seizures on follow-up 3, 6.
• However, other studies found that phenytoin reaches therapeutic levels in CSF quickly and may be effective for seizure prophylaxis in the acute setting 2.
• The choice between levetiracetam and phenytoin may depend on individual patient factors and the specific clinical scenario 3.

Duration of Antiseizure Medication Use

• The optimal duration of antiseizure medication use for seizure prophylaxis in TBI is not well established 3.
• Some studies suggest that a short duration of antiseizure medication use (≤ 7 days) may be sufficient for seizure prophylaxis in TBI 3, 4.
• However, other studies found that longer durations of antiseizure medication use may be necessary to prevent late seizures 6.