Valproic Acid for Seizure Prophylaxis and Reduction of Headache Burden Following Subarachnoid Hemorrhage
Michael Wagner, Kristin Lanier, Jenna Sorgenfrei
Background: Aneurysmal subarachnoid hemorrhage (aSAH) management includes possible surgical intervention, blood pressure control, management of hydrocephalus, vasospasm prevention, and seizure prophylaxis. Guidelines do not currently recommend a specific seizure prophylaxis agent for aSAH. Levetiracetam is commonly selected in favor of the benign side effect profile and overall patient tolerability, yet it does not address any additional symptoms of aSAH. Valproic acid not only provides seizure prophylaxis but has demonstrated benefits in both migraine prophylaxis and headache treatment. The objective of this study is to determine if switching from levetiracetam to valproic acid reduces headache burden in patients based on utilization of pain medication for breakthrough symptoms
Methods: A single-center, retrospective, cohort study identified adult patients admitted to the neurological intensive care unit of Prisma Health-Upstate between September 1, 2023 to September 1, 2025 with a diagnosis of aneurysmal subarachnoid hemorrhage. Seizure prophylaxis with levetiracetam was compared to valproic acid to determine the difference in overall headache burden based on breakthrough pain medication administration. Secondary outcomes include seizure incidence, intensive care unit length of stay, transcranial doppler changes, and incidence of adverse effects
Results: A total of 115 patients were included with 66 in the levetiracetam group and 49 in the valproic acid group. Patients were prescribed similar pain regimens including scheduled gabapentin, lidocaine patches, and acetaminophen as needed in both the valproic acid group and levetiracetam (39.4% vs. 67.3%). For the primary outcome of daily headache incidence, there was a statically significant difference in favor of the levetiracetam group (3.0 vs. 2.4, P = 0.02). Additionally, patients in the valproic acid group demonstrated more frequent use of both as needed and breakthrough pain medication utilization. No differences were found in adverse effects.
Conclusions:Seizure prophylaxis with valproic acid did not reduce headache incidence or pain medication utilization following nontraumatic subarachnoid hemorrhage. These findings support the use of either valproic acid or levetiracetam as seizure prophylaxis, with no added benefit seen in the valproic acid group.
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