From the Guidelines
Prophylactic anti-epileptic drugs (AEDs) are not recommended for primary prevention of post-traumatic seizures in Traumatic Brain Injury (TBI) patients.
Rationale
- The incidence of early clinical seizures is relatively low, at 2.2% 208, and the use of AEDs has not been shown to significantly reduce the occurrence of early or delayed post-traumatic seizures 1.
- Eleven clinical trials, including two meta-analyses, found no significant effect of AEDs in preventing post-traumatic seizures, with some studies even showing increased side effects or worsening neurological outcomes 1.
- The use of phenytoin, a commonly used AED, has been associated with increased side effects and a lower degree of tolerance compared to levetiracetam 1.
Exceptions
- AEDs may be considered in patients with specific risk factors, such as chronic subdural hematoma or a past history of epilepsy 1.
- In such cases, levetiracetam is preferred over phenytoin due to its higher degree of tolerance 1.
From the Research
Role of Prophylactic Anti-Epileptic Drugs in Traumatic Brain Injury
The use of prophylactic anti-epileptic drugs (AEDs) in traumatic brain injury (TBI) is a topic of ongoing debate. Several studies have investigated the effectiveness of AEDs in preventing post-traumatic seizures (PTS) in patients with TBI.
Efficacy of AEDs in Preventing PTS
- A systematic review and meta-analysis published in 2019 found that the use of AEDs, particularly phenytoin, levetiracetam, and valproate, was associated with a trend towards a protective effect against early PTS, although the evidence was modest 2.
- A study published in 2003 found that phenytoin prophylaxis was effective in decreasing the risk of early post-traumatic seizures, but not late post-traumatic seizures 3.
- A retrospective observational study published in 2013 found that levetiracetam was increasingly being used as an alternative to phenytoin for seizure prophylaxis in TBI patients, although no published data validated its comparable efficacy 4.
Duration of AED Prophylaxis
- The American Academy of Neurology recommends that AED prophylaxis should be started for patients with severe TBI and discontinued after 1 week 3.
- A study published in 2016 found that the use of AED prophylaxis varied widely and was generally inconsistent with evidence-based guidance, with many patients receiving prophylaxis for longer than the recommended 1 week 5.
Impact of AED Prophylaxis on Outcome
- A study published in 2021 found that the use of anti-seizure medication (ASM) was associated with a worse rehabilitation outcome, independently of the onset of epilepsy during treatment 6.
- The same study found that late post-traumatic seizures (LPTS) were associated with a significantly higher risk of worse neurological and rehabilitation outcomes, whereas early post-traumatic seizures (EPTS) did not influence outcome 6.