Levetiracetam may be effective to prevent seizures in spontaneous intracerebral hemorrhage

Levetiracetam was safe and may be effective in preventing acute seizures in patients with spontaneous intracerebral hemorrhage, according to clinical trial results in The Lancet Neurology.

“Randomized controlled trials supporting the use of antiseizure medication as primary prevention among patients with intracerebral hemorrhage are scarce,” Laure Peter-Derex, MD, of the Center for Sleep Medicine and Respiratory Diseases at Croix-Rousse Hospital in France, and colleagues wrote. “Accordingly, clinical guidelines do not recommend the use of prophylactic antiseizure medication in patients with acute intracerebral hemorrhage.”

Seeking to determine whether prophylactic levetiracetam could reduce the risk for acute seizures in these patients, Peter-Derex and colleagues conducted a randomized, placebo-controlled phase 3 trial at three stroke units in France. They included 50 participants, aged 18 years or older, no more than 24 hours after onset of mild to moderate, nontraumatic intracerebral hemorrhage.

Participants were randomly assigned on a 1:1 basis to receive 500 mg of IV levetiracetam every 12 hours (n =24) or placebo (n = 26) for 6 weeks. Continuous electroencephalogram (EEG) was started within 24 hours and recorded over 48 hours. The primary outcome was at least one clinical seizure within 72 hours of inclusion or at least one electrographic seizure recorded on continuous EEG.

Results showed that during the first 72 hours, a clinical or electrographic seizure was reported in three of 19 patients in the levetiracetam group compared with 10 of 23 patients in the placebo group (OR, 0.16; 95% CI, 0.03-0.94). Within the first 72 hours, all seizures were only electrographic seizures.

Researchers reported no significant difference in depression or anxiety between the groups at 1 month or 3 months, with depression reported in three levetiracetam patients and four placebo patients, and anxiety in two and one, respectively.

Compared with the placebo group, the most common treatment-emergent adverse events in the levetiracetam group were headache (24% placebo vs. 39% drug), pain (40% vs. 13%) and falls (16% vs. 30%).

Serious adverse events were limited to neurological deterioration because of intracerebral hemorrhage, as well as severe pneumonia. No treatment-related deaths were reported in either group.

Although Peter-Derex and colleagues determined that levetiracetam “might be effective” in preventing acute seizures in patients with spontaneous intracerebral hemorrhage, they acknowledged that given the trial’s small sample size and limitations on continuous EEG data, “an adequately powered randomized controlled trial is needed to answer whether primary seizure prophylaxis improves functional outcome in this setting.”