LEV-BRV Safety Meta-Analysis
(2026)Objective
To compare the adverse event profiles of levetiracetam and brivaracetam versus placebo using systematic review and meta-analysis of randomized controlled trials.
Study Summary
• Levetiracetam was additionally associated with irritability (OR 2.55) and asthenia (OR 1.71)
• Brivaracetam carried higher risk of dizziness (OR 1.75) and fatigue (OR 2.14)
• Indirect comparisons found no statistically significant differences between the two agents overall
Intervention
Levetiracetam vs. brivaracetam vs. placebo — systematic review and meta-analysis of 96 RCTs
Inclusion Criteria
Randomized controlled trials of levetiracetam or brivaracetam reporting adverse events
Study Design
Arms: Levetiracetam (n=7,145) vs. Brivaracetam (n=2,549) vs. Placebo (not separately reported)
Patients per Arm: LEV: 7,145; BRV: 2,549
Outcome
• LEV uniquely associated with irritability (OR 2.55) and asthenia (OR 1.71)
• BRV uniquely associated with dizziness (OR 1.75) and fatigue (OR 2.14)
• No statistically significant head-to-head differences on indirect comparison
Bottom Line
Both SV2A agents increase somnolence; clinicians should counsel patients that levetiracetam carries specific risks of irritability and asthenia, while brivaracetam is more associated with dizziness and fatigue, though no statistically significant head-to-head differences were confirmed on indirect comparison.
Major Points
- 96 RCTs were included, with 7,145 levetiracetam-exposed and 2,549 brivaracetam-exposed patients
- Both LEV (OR 1.80) and BRV (OR 1.86) significantly increased somnolence risk versus placebo
- Levetiracetam was associated with irritability (OR 2.55) and asthenia (OR 1.71) — risks not shared by brivaracetam
- Brivaracetam was associated with dizziness (OR 1.75) and fatigue (OR 2.14) — risks not highlighted for levetiracetam
- Indirect comparisons between LEV and BRV found no statistically significant overall differences in adverse event profiles
- The distinct side-effect signatures may inform individualized drug selection based on patient comorbidities and tolerability concerns
Study Design
- Study Type
- Systematic review and meta-analysis of randomized controlled trials
- Randomization
- Yes
- Sample Size
- 9694
Primary Outcome
Definition: Adverse event profiles of levetiracetam and brivaracetam versus placebo, and indirect comparison between the two agents
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Placebo | Levetiracetam and Brivaracetam | - |
Limitations & Criticisms
- Indirect comparisons are methodologically weaker than head-to-head RCTs and cannot confirm equivalence
- Pooling across 96 RCTs introduces heterogeneity in patient populations, doses, and epilepsy subtypes
- Abstract-level data limits assessment of dose-response relationships and severity grading of adverse events
Citation
Journal of Neurology, March 2026. DOI: 10.1007/s00415-026-13746-9