Rowe AS, et al. *Neurocritical Care*. 2026;45(1):34–57. DOI: [10.1007/s12028-026-02522-2](https://doi.org/10.1007/s12028-026-02522-2)
Antiseizure prophylaxis after supratentorial surgery remains highly variable, particularly in patients who have never experienced a seizure. This Neurocritical Care Society guideline examines whether prophylaxis is justified, which drug should be chosen and how long treatment should continue. The evidence does not establish a universal benefit for routine medication. When prophylaxis is selected, levetiracetam appears preferable to phenytoin and treatment should generally remain brief. The recommendations emphasize individualized decisions and acknowledge the low certainty of the available evidence.
Objective
To determine whether adults without a previous clinical or electrographic seizure should receive prophylactic antiseizure medication after supratentorial neurosurgery and, when prophylaxis is selected, which agent and duration should be preferred.
Methods
The Neurocritical Care Society performed a systematic review and meta-analysis using GRADE methodology. Three clinical questions were evaluated: antiseizure medication versus no prophylaxis; levetiracetam versus phenytoin or fosphenytoin; and short-duration treatment (7 days or less) versus longer treatment. The principal outcomes were early seizures, late seizures, adverse events, mortality and functional or cognitive outcomes. Of 1,988 records identified, 16 studies informed the recommendations and 15 were included in meta-analyses.
Main results
Randomized trials suggested a reduction in early seizures with prophylactic medication, but the effect was no longer significant when all study designs were pooled. Prophylaxis did not reduce late seizures or mortality and showed a nonsignificant trend toward more adverse events.
When medication was used, levetiracetam was associated with fewer early seizures than phenytoin, with trends toward fewer late seizures and adverse events. Only three studies compared treatment duration, and none demonstrated a significant seizure benefit from continuing prophylaxis beyond 7 days.
The panel therefore issued conditional recommendations allowing either prophylaxis or no prophylaxis, favoring levetiracetam when an agent is chosen and favoring a course of 7 days or less rather than prolonged treatment.
Interpretation
Routine prophylaxis cannot be considered mandatory for every seizure-naive patient undergoing supratentorial surgery. The decision should reflect individual seizure risk, pathology, cortical involvement, operative factors and the consequences of a postoperative seizure. If prophylaxis is considered appropriate, levetiracetam for a short perioperative course is the most defensible default strategy.
Limitations
The certainty of evidence was low for medication versus no medication and very low for drug selection and duration. Studies varied substantially in pathology, surgical procedure, dosing and seizure definitions. Evidence about cognition, function and patient-reported outcomes was particularly limited.
Clinical takeaway
Do not extend antiseizure prophylaxis automatically after supratentorial surgery in a patient with no previous seizure. Individualize the indication; if medication is used, levetiracetam and a course no longer than 7 days are generally preferable, unless the postoperative clinical course creates a new indication for treatment.