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

Kanner AM, Bicchi MM (2022) Antiseizure medications for adults with epilepsy: a review. JAMA 327:1269–1281. https://doi.org/10.1001/jama.2022.3880

Article  CAS  PubMed  Google Scholar 

Collaborators GBDE (2025) Global, regional, and national burden of epilepsy, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Public Health 10:e203–e227. https://doi.org/10.1016/S2468-2667(24)00302-5

Article  Google Scholar 

Welton JM, Walker C, Riney K, Ng A, Todd L, D’Souza WJ (2020) Quality of life and its association with comorbidities and adverse events from antiepileptic medications: online survey of patients with epilepsy in Australia. Epilepsy Behav 104:106856. https://doi.org/10.1016/j.yebeh.2019.106856

Article  PubMed  Google Scholar 

Perucca P, Gilliam FG (2012) Adverse effects of antiepileptic drugs. Lancet Neurol 11:792–802. https://doi.org/10.1016/S1474-4422(12)70153-9

Article  CAS  PubMed  Google Scholar 

Mao J, Takahashi K, Cheng M, Xu C, Boca A, Song Y, Dandurand A (2024) Real-world anti-seizure treatment and adverse events among individuals living with drug-resistant focal epilepsy in the United States. Epilepsia Open 9:1311–1320. https://doi.org/10.1002/epi4.12967

Article  PubMed  PubMed Central  Google Scholar 

Giussani G, Bianchi E, Canelli V, Erba G, Franchi C, Nobili A, Sander JW, Beghi E (2017) Antiepileptic drug discontinuation by people with epilepsy in the general population. Epilepsia 58:1524–1532. https://doi.org/10.1111/epi.13853

Article  CAS  PubMed  Google Scholar 

Compagno Strandberg M, Soderberg-Lofdal K, Kimland E, Dahlin M, Kallen K (2020) Evidence-based anti-seizure monotherapy in newly diagnosed epilepsy: a new approach. Acta Neurol Scand 142:323–332. https://doi.org/10.1111/ane.13312

Article  PubMed  Google Scholar 

Wright C, Downing J, Mungall D, Khan O, Williams A, Fonkem E, Garrett D, Aceves J, Kirmani B (2013) Clinical pharmacology and pharmacokinetics of levetiracetam. Front Neurol 4:192. https://doi.org/10.3389/fneur.2013.00192

Article  PubMed  PubMed Central  Google Scholar 

Barnard SN, Chen Z, Kanner AM, Holmes MG, Klein P, Abou-Khalil BW, Gidal BE, French J, Perucca P (2024) The adverse effects of commonly prescribed antiseizure medications in adults with newly diagnosed focal epilepsy. Neurology 103:e209821. https://doi.org/10.1212/wnl.0000000000209821

Article  PubMed  Google Scholar 

Zhang JF, Piryani R, Swayampakula AK, Farooq O (2022) Levetiracetam-induced aggression and acute behavioral changes: a case report and literature review. Clin Case Rep 10:e05586. https://doi.org/10.1002/ccr3.5586

Article  PubMed  PubMed Central  Google Scholar 

Verrotti A, Prezioso G, Di Sabatino F, Franco V, Chiarelli F, Zaccara G (2015) The adverse event profile of levetiracetam: a meta-analysis on children and adults. Seizure 31:49–55. https://doi.org/10.1016/j.seizure.2015.07.004

Article  PubMed  Google Scholar 

Gillard M, Fuks B, Leclercq K, Matagne A (2011) Binding characteristics of brivaracetam, a selective, high affinity SV2A ligand in rat, mouse and human brain: relationship to anti-convulsant properties. Eur J Pharmacol 664:36–44. https://doi.org/10.1016/j.ejphar.2011.04.064

Article  CAS  PubMed  Google Scholar 

Hwang H, Kim WJ (2025) Brivaracetam: pharmacology, clinical efficacy, and safety in epilepsy. J Epilepsy Res 15:42–55. https://doi.org/10.14581/jer.25005

Article  PubMed  PubMed Central  Google Scholar 

NICE (2025) Epilepsies in children, young people and adults. https://www.nice.org.uk/guidance/ng217/resources/epilepsies-in-children-young-people-and-adults-pdf-66143780239813. Accessed 16 Aug 2025

Zhu LN, Chen D, Chen T, Xu D, Chen SH, Liu L (2017) The adverse event profile of brivaracetam: a meta-analysis of randomized controlled trials. Seizure 45:7–16. https://doi.org/10.1016/j.seizure.2016.11.008

Article  CAS  PubMed  Google Scholar 

Fonseca E, Guzman L, Quintana M, Abraira L, Santamarina E, Salas-Puig X, Toledo M (2020) Efficacy, retention, and safety of brivaracetam in adult patients with genetic generalized epilepsy. Epilepsy Behav 102:106657. https://doi.org/10.1016/j.yebeh.2019.106657

Article  PubMed  Google Scholar 

Zhang L, Li S, Li H, Zou X (2016) Levetiracetam vs. brivaracetam for adults with refractory focal seizures: a meta-analysis and indirect comparison. Seizure 39:28–33. https://doi.org/10.1016/j.seizure.2016.05.004

Article  PubMed  Google Scholar 

Nicolas JM, Hannestad J, Holden D, Kervyn S, Nabulsi N, Tytgat D, Huang Y, Chanteux H, Staelens L, Matagne A, Mathy FX, Mercier J, Stockis A, Carson RE, Klitgaard H (2016) Brivaracetam, a selective high-affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action. Epilepsia 57:201–209. https://doi.org/10.1111/epi.13267

Article  CAS  PubMed  Google Scholar 

Wood MD, Gillard M (2017) Evidence for a differential interaction of brivaracetam and levetiracetam with the synaptic vesicle 2A protein. Epilepsia 58:255–262. https://doi.org/10.1111/epi.13638

Article  CAS  PubMed  Google Scholar 

Wu PP, Cao BR, Tian FY, Gao ZB (2024) Development of SV2A ligands for epilepsy treatment: a review of levetiracetam, brivaracetam, and padsevonil. Neurosci Bull 40:594–608. https://doi.org/10.1007/s12264-023-01138-2

Article  PubMed  Google Scholar 

Steinhoff BJ, Klein P, Klitgaard H, Laloyaux C, Moseley BD, Ricchetti-Masterson K, Rosenow F, Sirven JI, Smith B, Stern JM, Toledo M, Zipfel PA, Villanueva V (2021) Behavioral adverse events with brivaracetam, levetiracetam, perampanel, and topiramate: a systematic review. Epilepsy Behav 118:107939. https://doi.org/10.1016/j.yebeh.2021.107939

Article  PubMed  Google Scholar 

Song T, Feng L, Xia Y, Pang M, Geng J, Zhang X, Wang Y (2023) Safety and efficacy of brivaracetam in children epilepsy: a systematic review and meta-analysis. Front Neurol 14:1170780. https://doi.org/10.3389/fneur.2023.1170780

Article  PubMed  PubMed Central  Google Scholar 

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hrobjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71. https://doi.org/10.1136/bmj.n71

Article  PubMed  PubMed Central  Google Scholar 

(MSSO) MMaSSO (2024) Introductory guide to MedDRA version 27.0. https://admin.meddra.org/sites/default/files/guidance/file/intguide_27_0.pdf. Accessed 16 Aug 2025

Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng HY, Corbett MS, Eldridge SM, Emberson JR, Hernan MA, Hopewell S, Hrobjartsson A, Junqueira DR, Juni P, Kirkham JJ, Lasserson T, Li T, McAleenan M, Reeves BC, Shepperd S, Shrier I, Stewart LA, Tilling K, White IR, Whiting PF, Higgins JPT (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 366:l4898. https://doi.org/10.1136/bmj.l4898

Article  PubMed  Google Scholar 

Riemer TG, Villagomez Fuentes LE, Algharably EAE, Schafer MS, Mangelsen E, Furtig MA, Bittner N, Bar A, Zaidi Touis L, Wachtell K, Majic T, Dinges MJ, Kreutz R (2021) Do beta-blockers cause depression?: Systematic review and meta-analysis of psychiatric adverse events during beta-blocker therapy. Hypertension 77:1539–1548. https://doi.org/10.1161/HYPERTENSIONAHA.120.16590

Article  CAS  PubMed  Google Scholar 

Jackson D, Turner R (2017) Power analysis for random-effects meta-analysis. Res Synth Methods 8:290–302. https://doi.org/10.1002/jrsm.1240

Article  PubMed  PubMed Central  Google Scholar 

Collaboration TC (2025) Review manager (RevMan) [Computer program]. Version 9.5.2. In: The Cochrane Collaboration

Doi SA, Furuya-Kanamori L, Xu C, Lin L, Chivese T, Thalib L (2022) Controversy and debate: questionable utility of the relative risk in clinical research: Paper 1: a call for change to practice. J Clin Epidemiol 142:271–279. https://doi.org/10.1016/j.jclinepi.2020.08.019

Article  PubMed  Google Scholar 

Deeks JJ, Higgins JPT, Altman DG, McKenzie JE, Veroniki AA. (2024) Chapter 10: analysing data and undertaking meta-analyses [last updated november 2024]. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (ed) Cochrane handbook for systematic reviews of interventions, version 6.5. Cochrane

Team RC (2025) R: a language and environment for statistical computing. In: R Foundation for Statistical Computing, Vienna, Austria

Viechtbauer W (2025) metafor: Meta-analysis package for R, Version: 4.8–0. In: CRAN

Pandya R, Sundaram PK, Baghel SS (2024) Comparison of effectiveness of brivaracetam and levetiracetam for prophylaxis of early post-traumatic seizures: a prospective comparative interventional study. Asian J Neurosurg 19:728–734. https://doi.org/10.1055/s-0044-1790516

Article  PubMed  PubMed Central 

Comments (0)

No login
gif