Reassessing the adverse event profiles of levetiracetam and brivaracetam: a systematic review and meta-analysis.

Emma Fröling, Mariel Morales Sahm, Marcel Schmude, Charlotte P Assies, Michael Wittenberg, Felix Rosenow, Felix Bermpohl, Thomas G Riemer

Journal: Journal of neurology 2026;273(3):

PMID: 41824075

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Abstract

OBJECTIVE

To synthesize adverse event (AE) data from randomized controlled trials (RCTs) of levetiracetam (LEV) and brivaracetam (BRV), compare their safety profiles, and identify moderators of AE risk.

METHODS

We conducted a systematic review and meta-analysis of RCTs of LEV or BRV, searching PubMed, Web of Science, and ClinicalTrials.gov to August 2025. AE frequencies were summarized qualitatively, and random-effects meta-analyses compared LEV and BRV with placebo. Additional analyses compared LEV and BRV and assessed moderators.

PROSPERO

CRD42023491050, CRD420251003207.

RESULTS

Ninety-six RCTs including 7145 patients exposed to LEV and 2549 to BRV were analyzed. Qualitative synthesis identified headache, somnolence, dizziness, and fatigue as the most common AEs, with higher frequencies of some psychiatric AEs (e.g., irritability, aggression) reported for LEV. Meta-analyses showed increased somnolence with both LEV (OR 1.80, 95% CI [1.41-2.30]) and BRV (OR 1.86, 95% CI [1.33-2.61]). LEV was additionally associated with irritability (OR 2.55, 95% CI [1.41-4.63]) and asthenia (OR 1.71, 95% CI [1.15-2.54]), whereas BRV was associated with dizziness (OR 1.75, 95% CI [1.24-2.46]) and fatigue (OR 2.14, 95% CI [1.43-3.20]). Few moderators of AE risk were identified, and no significant differences emerged between LEV and BRV in indirect comparisons.

CONCLUSION

LEV and BRV show favorable safety profiles that appear comparable based on meta-analytic findings, despite higher rates of some psychiatric AEs with LEV on a descriptive level. Both remain safe treatment options, though larger head-to-head trials are needed to provide definitive comparative evidence.

Address: Department of Psychiatry and Psychotherapy, Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10115, Berlin, Germany.; Institute of Clinical Pharmacology and Toxicology, Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10117, Berlin, Germany.; Institute of Psychology, Heidelberg University, 69117, Heidelberg, Germany.; Department Marburg, Faculty of Medicine, Coordinating Center of Clinical Trials, Marburg University, 35043, Marburg, Germany.; Department of Neurology, Epilepsy Center Frankfurt Rhine-Main, Universitätsmedizin Frankfurt, Goethe-Universität Frankfurt, 60590, Frankfurt, Germany.; Department of Psychiatry and Psychotherapy, Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10115, Berlin, Germany. [email protected].; Institute of Clinical Pharmacology and Toxicology, Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10117, Berlin, Germany. [email protected].

DOI: 10.1007/s00415-026-13746-9

MeSH Terms: Humans, Levetiracetam, Anticonvulsants, Randomized Controlled Trials as Topic, Pyrrolidinones, Dizziness