Routine prophylactic use of levetiracetam after mild traumatic brain injury (TBI) may offer no protection against epilepsy while exposing patients to potentially significant side effects, new research suggests.
The analysis of more than 50,000 patients found that levetiracetam only reduced the risk of early post-traumatic epilepsy in patients with severe TBI, and did not lower the risk of epilepsy over the following year regardless of severity.
However, use of the drug was associated with an increased risk of metabolic, cognitive and psychiatric adverse events.
“To our knowledge, this is the largest analysis of prophylactic levetiracetam to date, and it upholds that the benefits of prophylaxis may be restricted to the most severe injuries, whereas routine use in mild TBI offers no measurable protection and exposes patients to potential harm,” wrote the authors, led by Isaac Thorman of New York Medical College.
“By delineating this severity-specific risk–benefit profile, our results reaffirm that prophylaxis should be reserved for patients with severe TBI or other high-risk features, and they underscore the need to re-evaluate existing seizure prevention guidelines,” they added.
The study, published in the Annals of Neurology [link here], analysed data on US patients (n=51,263) within the TriNetX Research Network who experienced a first TBI and had a Glasgow Coma Scale (GCS) score recorded, excluding those with pre-existing epilepsy, seizures on the day of injury, or prior levetiracetam exposure.
Across the whole cohort, 14,630 patients (30%) received prophylactic levetiracetam and 6.7% developed epilepsy.
After adjusting for age, sex and type of injury, patients treated with levetiracetam had a similar risk of developing epilepsy within seven days post-injury as those who did not receive any antiseizure medications (ASMs, p=0.300).
Across the whole cohort, patients treated with levetiracetam did not have a higher risk of epilepsy in the year after injury than those who were not given ASMs (p=0.600).
In patients with severe TBI (GCS 3–8; n = 10,805), levetiracetam reduced the risk of early epilepsy (HR 0.55, p=0.04) but not late epilepsy (HR 0.90, p=0.45), compared to no ASMs.
In patients with mild TBI (GCS 13–15; n = 33,625), levetiracetam prophylaxis did not reduce the risk of early epilepsy (HR 0.85, p=0.61) or late epilepsy (HR 1.00, p=0.997), compared to no ASMs.
Across all patient groups, older age, cerebral oedema and subdural haemorrhage increased the risk of epilepsy.
Abnormal movements and gait disturbances were significant risk factors for late post-traumatic epilepsy in patients with mild TBI, but not those with severe TBI.
Over five years of follow-up, patients who were prescribed levetiracetam on the day of their injury had a higher unadjusted risk of mortality than those who were not (20.4% vs 18.2%, p<0.001).
Those prescribed levetiracetam also had a higher risk of memory and awareness impairment, metabolic disorders, migraines and headaches, anxiety and depression, sleep disorders, fever, and visual disturbances (all p<0.001).
“Future prospective studies should further define which subgroups derive the greatest net benefit and whether tailored dosing or duration strategies might optimise outcomes,” the authors wrote.
“Until such evidence emerges, clinicians should weigh the limited, short-term protection against the real potential for adverse effects when considering levetiracetam for seizure prophylaxis after TBI,” they concluded.