Home›Emergency Medicine› Levetiracetam lowers early seizure risk versus phenytoin after neurosurgery, but evidence is weak
Levetiracetam lowers early seizure risk versus phenytoin after neurosurgery, but evidence is weakLevetiracetam Shows Potential for Preventing Early Post-Surgery Seizures
Neurocritical carePublished August 3, 2026Study authors: Rowe A Shaun, Ullman Jamie, Johnson Emily L, Gilmore Emily J, Olson DaiWai, Rayi Appaji, Tesoro Elji…PubMed ↗DOI ↗Editorial oversight: Dr. Lars van Dijk, PhD · Surgical, Procedural & Diagnostic
AI-generated summary of the cited source, checked by automated accuracy review.
How we work
Share
Key Takeaway
Consider LEV for short-term seizure prophylaxis after neurosurgery, but weigh weak evidence and adverse event trends.
This meta-analysis evaluated the efficacy and safety of antiseizure medication (ASM) prophylaxis in adults hospitalized following supratentorial neurosurgery with no prior seizure history. The analysis compared ASM versus no ASM, levetiracetam (LEV) versus phenytoin/fosphenytoin (PHT), and long (> 7 days) versus short (≤ 7 days) prophylaxis duration. The primary outcome was early seizure (≤ 14 days); secondary outcomes included late seizures (> 14 days), adverse events, mortality, functional outcomes, and cognitive outcomes.
For early seizure prevention, the meta-analysis of RCTs showed a significant benefit with ASM prophylaxis, but meta-analyses including all study designs showed a nonsignificant effect. No differences were found for late seizures or mortality. There was a trend toward higher adverse event rates with ASM prophylaxis overall.
When LEV was compared directly with PHT, LEV was associated with significantly lower early seizure rates. Trends also favored LEV for fewer late seizures and fewer adverse events. However, the quality of evidence for these comparisons was rated very low. For short versus long duration of prophylaxis, no significant difference in seizure events was observed, but the evidence quality was also very low.
The authors issued conditional recommendations: either ASM or no ASM may be used; if ASM is chosen, LEV is preferred over PHT; and if ASM is used, a short duration is preferred. These recommendations are based on low or very low quality of evidence, and the authors caution against overstating the benefits. The analysis did not report sample sizes, follow-up duration, or pooled effect sizes, limiting quantitative interpretation.
How this fits prior evidence
This meta-analysis extends prior coverage by focusing on adults after supratentorial neurosurgery, a population distinct from pediatric epilepsy and stroke. It confirms the benefit of levetiracetam for early seizure prevention, aligning with prior findings of LEV efficacy, but it also notes no consistent advantage over active comparators, similar to the pediatric review. The trend toward adverse events with ASM echoes the psychobehavioral adverse effects noted in epilepsy. The lower early seizure rate with LEV versus PHT adds specificity, though the very low evidence quality tempers conclusions.
Researchers looked at how different medications help patients avoid seizures after undergoing supratentorial neurosurgery. The study specifically compared the use of levetiracetam against phenytoin or fosphenytoin, as well as the impact of using these medicines for a short period versus a longer period.
The analysis found that levetiracetam was associated with lower rates of early seizures occurring within 14 days of surgery. While there were no significant differences in late seizures or mortality rates between the groups, there was a trend toward fewer adverse events when patients took levetiracetam instead of phenytoin. The length of time the medication was given did not show a significant difference in outcomes.
It is important to note that the evidence for these specific findings is of very low quality. Because the data is limited and based on a meta-analysis of various study designs, these results should be viewed as preliminary. Patients and doctors should discuss these options carefully to determine the best treatment plan based on individual needs.
What this means for you:
Levetiracetam may reduce early post-surgery seizures, but evidence for this finding is currently very low quality.
Common questions
Is levetiracetam more effective than phenytoin for preventing seizures?
The analysis showed that levetiracetam was associated with significantly lower rates of early seizures (within 14 days) compared to phenytoin. However, the evidence supporting this specific finding is considered very low quality by researchers.
Are there side effects when taking these medications?
There was a general trend toward higher rates of adverse events for those taking any anti-seizure medication (ASM). However, there was a specific trend toward fewer adverse events when levetiracetam was used instead of phenytoin.
Does the length of treatment affect seizure prevention?
The study found no significant difference in seizure events when comparing a short duration (7 days or less) to a long duration of medication. Because the evidence for this finding is very low quality, it is not yet clear how timing affects outcomes.
BACKGROUND: There is significant heterogeneity related to the use of prophylactic antiseizure medications (ASM) following supratentorial craniotomy.
METHODS: We conducted a systematic review and meta-analysis assessing ASM primary prophylaxis in adults hospitalized following supratentorial neurosurgery with no prior seizure history. The following population, intervention, comparator, and outcome (PICO) questions were assessed: (1) Should ASM versus no ASM be used as seizure prophylaxis in adult patients undergoing supratentorial neurosurgery? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT) be preferentially used? and (3) Should a long (> 7 days) versus short (≤ 7 days) duration of prophylaxis be used? The main outcomes were early seizure (≤ 14 days), late seizures (> 14 days), adverse events, mortality, and functional and cognitive outcomes. We utilized Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to generate recommendations.
RESULTS: The initial literature search yielded 1988 articles, and 16 formed the basis of the recommendations. PICO 1: while meta-analysis of randomized controlled trials (RCTs) demonstrated a significant benefit for early seizure prevention, meta-analyses including all study designs was nonsignificant. Further, there were no differences in late seizure or mortality rates, and there was a trend toward higher adverse event rates with ASM. PICO 2: LEV was associated with significantly lower early seizure rates than PHT, and there were trends toward fewer late seizures and adverse events with LEV. PICO 3: only three studies examined the duration of ASM treatment, and there was no significant difference in seizure events between subjects treated for a short versus long duration.
CONCLUSIONS: We suggest that either prophylactic ASM or no ASM be used for seizure prophylaxis in patients undergoing supratentorial neurosurgery (conditional recommendation, low quality of evidence). If an ASM is used, we suggest LEV over PHT (conditional recommendation, very low quality of evidence) for a short duration (conditional recommendation, very low quality of evidence).
