Levetiracetam monotherapy for new-onset epilepsy in middle-aged and elderly patients: a meta-analysis_Journal of Epilepsy

Authors：

 SHEN Yijian , SHI Qingxiao

Department of Neurology, Jinjiang Municipal Hospital (Shanghai Sixth People's Hospital Fujian), Jinjiang 362200, China;

Corresponding?author：

SHEN Yijian, Email: 348059904@qq.com

Keywords：

Levetiracetam; Middle-aged and elderly; New-onset epilepsy; Monotherapy; Antiseizure medications; Meta-analysis

DOI：

10.7507/2096-0247.202605007

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Objective To evaluate the efficacy and safety of levetiracetam (LEV) monotherapy for new-onset epilepsy in middle-aged and elderly patients (aged ≥40 years). Methods PubMed, Embase, Cochrane Library, CNKI, and Wanfang were searched through December 31, 2025 for RCTs comparing LEV versus other antiseizure medcations (ASMs) monotherapy in patients aged ≥40 years. Cochrane RoB 2.0 and random-effects models (DerSimonian-Laird) were used to assess bias and pool risk ratios (RR). Results A total of 9 randomized controlled trials (RCTs) were enrolled, involving 1 152 participants (575 in the LEV group and 577 in the control group). The participants were aged 40–95 years with a follow-up duration of 6–58 months. The control medications included oxcarbazepine (OXC, 4 trials), carbamazepine (CBZ, 3 trials), and controlled-release carbamazepine (CR-CBZ, 2 trials). Pooled overall response rate analysis across all 9 trials demonstrated superior efficacy in the LEV group compared with the control group [relative risk (RR) = 1.192, 95% confidence interval (CI) (1.131, 1.257), Z=6.57, P<0.001, I²=0.0%]. Subgroup analyses yielded consistent results: LEV vs. OXC (4 trials, RR=1.185, 95%CI (1.093, 1.285), I²=0.0%) and LEV vs. CBZ/CR-CBZ (5 trials, RR=1.209, 95%CI (1.111, 1.316), I²=27.9%). The 12-month seizure-free rate was assessed in 5 trials with 845 subjects, showing a significantly higher rate in the LEV group [RR=1.130, 95%CI (1.023, 1.248), P=0.016, I²=2.5%]. The adverse event rate, analyzed based on 5 trials enrolling 803 patients, was markedly lower in the LEV group [RR=0.586, 95%CI (0.388, 0.887), P=0.011, I²=45.4%]. Sensitivity analyses by sequential exclusion of individual studies confirmed stable pooled outcomes. Conclusion LEV monotherapy shows better efficacy and fewer adverse events than traditional ASMs in middle-aged and elderly patients with new-onset epilepsy. Confirmatory international multicenter RCTs are needed.

Citation： SHEN Yijian, SHI Qingxiao. Levetiracetam monotherapy for new-onset epilepsy in middle-aged and elderly patients: a meta-analysis. Journal of Epilepsy, 2026, 12(5): 400-408. doi: 10.7507/2096-0247.202605007 Copy

1.	Fiest KM, Sauro KM, Wiebe S, et al. Prevalence and incidence of epilepsy: a systematic review and meta-analysis of international studies[J]. Neurology, 2017, 88(3): 296-303.
2.	Xue J, Li X, Zhao Y, et al. Global, regional, and national burden of idiopathic epilepsy in older adults, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021[J]. BMC Medicine, 2025, 23(1): 443.
3.	Pugh MJ, Knoefel JE, Mortensen EM, et al. New-onset epilepsy risk factors in older veterans[J]. Journal of the American Geriatrics Society, 2009, 57(2): 237-242.
4.	Ramsay RE, Rowan AJ, Pryor FM. Special considerations in treating the elderly patient with epilepsy [J]. Neurology, 2004, 62(5 Suppl 2): S24-S29.
5.	Chai X, Xiao Z, Zhao Q, et al. Cognitive impairment as a comorbidity of epilepsy in older adults: Analysis of global and domain-specific cognition[J]. Epileptic Disord, 2023, 25(1): 65-73.
6.	Hakami T. Neuropharmacology of antiseizure drugs[J]. Neuropsychopharmacol Rep, 2021, 41(3): 336-351.
7.	Fisher RS, Cross JH, French JA, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology[J]. Epilepsia, 2017, 58(4): 522-530.
8.	Piccenna L, Lopes Ferreira Pontes M, Alves Nogueira Fabris M, et al. Management of epilepsy in older adults: a critical review by the ILAE Task Force on Epilepsy in the elderly[J]. Epilepsia, 2023, 64(3): 567-585.
9.	Consoli D, Bosco D, Postorino P, et al. Levetiracetam versus carbamazepine in patients with late poststroke seizures: a multicenter prospective randomized open-label study (EpIC Project)[J]. Cerebrovascular Diseases, 2012, 34(4): 282-289.
10.	Werhahn KJ, Trinka E, Dobesberger J, et al. A randomized, double-blind comparison of antiepileptic drug treatment in the elderly with new-onset focal epilepsy[J]. Epilepsia, 2015, 56(3): 450-459.
11.	Pohlmann-Eden B, Marson AG, Noack-Rink M, et al. Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: subgroup analysis of the KOMET study[J]. BMC Neurology, 2016, 16(1): 149.
12.	Sterne JAC, Savovi? J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials[J]. BMJ, 2019, 366: l4898.
13.	Page MJ, Mckenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews[J]. BMJ, 2021, 372: n71.
14.	鄧宇春, 劉素萍, 李簡書, 等. 左乙拉西坦對中老年癲癇全面強直陣攣發作患者的療效及安全性分析[J]. 中國衛生標準管理, 2016, 7(36): 92-94.Deng YC, Liu SP, Li JS, et al. Efficacy and safety analysis of levetiracetam in middle-aged and elderly epilepsy patients with generalized tonic-clonic seizures[J]. China Health Standard Management, 2016, 7(36): 92-94.
15.	程乾. 左乙拉西坦治療中老年癲癇全面強直痙攣發作的臨床研究[J]. 現代診斷與治療, 2018, 29(20): 3283-3284.Cheng Q. Clinical study of levetiracetam in the treatment of generalized tonic-clonic seizures in middle-aged and elderly patients with epilepsy[J]. Modern Diagnosis & Treatment, 2018, 29(20): 3283-3284.
16.	劉風. 左乙拉西坦治療中老年癲癇全面強直陣攣發作患者的臨床效果 [J]. 中國民康醫學, 2020, 32(5): 12+5.Liu F. Clinical efficacy of levetiracetam for middle-aged and elderly epilepsy patients with generalized tonic-clonic seizures[J]. Medical Journal of Chinese People's Health, 2020, 32(5): 12+5.
17.	羅輝, 潘鑫, 張鵬, 等. 左乙拉西坦對中老年部分性發作癲癇的療效分析[J]. 中國繼續醫學教育, 2021, 13(30): 152-156.Luo H, Pan X, Zhang P, et al. Efficacy analysis of levetiracetam in middle-aged and elderly patients with partial-onset epilepsy[J]. China Continuing Medical Education, 2021, 13(30): 152-156.
18.	陳文東. 左乙拉西坦治療中老年癲癇全面強直陣攣發作的臨床療效及其對骨密度、骨代謝的影響[J]. 臨床醫藥文獻電子雜志, 2018, 5(87): 89-90.Chen WD. Clinical efficacy of levetiracetam in treating generalized tonic-clonic seizures among middle-aged and elderly epilepsy patients and its effects on bone mineral density and bone metabolism[J]. Electronic Journal of Clinical Medical Literature, 2018, 5(87): 89-90.
19.	孫慧靜, 陳凌, 陳克龍, 等. 左乙拉西坦在中老年癲癇患者中的治療效果以及對骨代謝的影響 [J]. 中國高等醫學教育, 2017(12): 133+142.Sun HJ, Chen L, Chen KL, et al. Therapeutic effect of levetiracetam and its influence on bone metabolism in middle-aged and elderly patients with epilepsy[J]. China Higher Medical Education, 2017(12): 133+142.
20.	Marson A, Burnside G, Appleton R, et al. The SANAD II study of the effectiveness and cost-effectiveness of levetiracetam, zonisamide, or lamotrigine for newly diagnosed focal epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial[J]. Lancet, 2021, 397(10282): 1363-1374.
21.	Anthony Marson, Girvan Burnside, et al. The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial[J]. Lancet, 2021, 397(10282): 1375-1386.
22.	Husein N, Langlois-Thérien T, Rioux B, et al. Medical and surgical treatment of epilepsy in older adults: a national survey[J]. Epilepsia, 2023, 64(4): 900-909.
23.	Abou-Khalil BW. Update on Antiseizure Medications 2022[J]. Continuum (Minneap Minn), 2022, 28(2): 500-535.
24.	Abou-Khalil BW. Update on Antiseizure Medications 2025[J]. Continuum (Minneap Minn), 2025, 31(1): 125-164.
25.	Chen Z, Brodie MJ, Kwan P. What has been the impact of new drug treatments on epilepsy?[J]. Current Opinion in Neurology, 2020, 33(2): 185-190.
26.	Zhang H, Ou Z, Zhang E, et al. Efficacy and safety of add-on antiseizure medications for focal epilepsy: a network meta-analysis[J]. Epilepsia Open, 2024, 9(4): 1550-1564.
27.	Peter-Derex L, Philippeau F, Garnier P, et al. Safety and efficacy of prophylactic levetiracetam for prevention of epileptic seizures in the acute phase of intracerebral haemorrhage (PEACH): a randomised, double-blind, placebo-controlled, phase 3 trial[J]. The Lancet Neurology, 2022, 21(9): 781-791.
28.	Sadeghi M, Eshraghi M, Akers KG, et al. Outcomes of status epilepticus and their predictors in the elderly—A systematic review[J]. Seizure, 2020, 81: 210-221.
29.	Wolcott ZC, Freund BE, Tatum WO, et al. Antiseizure medications for primary and secondary seizure prevention after stroke[J]. Frontiers in Neurology, 2025, 16: 1648064.
30.	Kawamura Y, Trinka E, Quinn TJ, et al. Pharmacological strategies for preventing post-stroke seizures and epilepsy[J]. Frontiers in Neurology, 2026, 16: 1709077.

1. Fiest KM, Sauro KM, Wiebe S, et al. Prevalence and incidence of epilepsy: a systematic review and meta-analysis of international studies[J]. Neurology, 2017, 88(3): 296-303.
2. Xue J, Li X, Zhao Y, et al. Global, regional, and national burden of idiopathic epilepsy in older adults, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021[J]. BMC Medicine, 2025, 23(1): 443.
3. Pugh MJ, Knoefel JE, Mortensen EM, et al. New-onset epilepsy risk factors in older veterans[J]. Journal of the American Geriatrics Society, 2009, 57(2): 237-242.
4. Ramsay RE, Rowan AJ, Pryor FM. Special considerations in treating the elderly patient with epilepsy [J]. Neurology, 2004, 62(5 Suppl 2): S24-S29.
5. Chai X, Xiao Z, Zhao Q, et al. Cognitive impairment as a comorbidity of epilepsy in older adults: Analysis of global and domain-specific cognition[J]. Epileptic Disord, 2023, 25(1): 65-73.
6. Hakami T. Neuropharmacology of antiseizure drugs[J]. Neuropsychopharmacol Rep, 2021, 41(3): 336-351.
7. Fisher RS, Cross JH, French JA, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology[J]. Epilepsia, 2017, 58(4): 522-530.
8. Piccenna L, Lopes Ferreira Pontes M, Alves Nogueira Fabris M, et al. Management of epilepsy in older adults: a critical review by the ILAE Task Force on Epilepsy in the elderly[J]. Epilepsia, 2023, 64(3): 567-585.
9. Consoli D, Bosco D, Postorino P, et al. Levetiracetam versus carbamazepine in patients with late poststroke seizures: a multicenter prospective randomized open-label study (EpIC Project)[J]. Cerebrovascular Diseases, 2012, 34(4): 282-289.
10. Werhahn KJ, Trinka E, Dobesberger J, et al. A randomized, double-blind comparison of antiepileptic drug treatment in the elderly with new-onset focal epilepsy[J]. Epilepsia, 2015, 56(3): 450-459.
11. Pohlmann-Eden B, Marson AG, Noack-Rink M, et al. Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: subgroup analysis of the KOMET study[J]. BMC Neurology, 2016, 16(1): 149.
12. Sterne JAC, Savovi? J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials[J]. BMJ, 2019, 366: l4898.
13. Page MJ, Mckenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews[J]. BMJ, 2021, 372: n71.
14. 鄧宇春, 劉素萍, 李簡書, 等. 左乙拉西坦對中老年癲癇全面強直陣攣發作患者的療效及安全性分析[J]. 中國衛生標準管理, 2016, 7(36): 92-94.Deng YC, Liu SP, Li JS, et al. Efficacy and safety analysis of levetiracetam in middle-aged and elderly epilepsy patients with generalized tonic-clonic seizures[J]. China Health Standard Management, 2016, 7(36): 92-94.
15. 程乾. 左乙拉西坦治療中老年癲癇全面強直痙攣發作的臨床研究[J]. 現代診斷與治療, 2018, 29(20): 3283-3284.Cheng Q. Clinical study of levetiracetam in the treatment of generalized tonic-clonic seizures in middle-aged and elderly patients with epilepsy[J]. Modern Diagnosis & Treatment, 2018, 29(20): 3283-3284.
16. 劉風. 左乙拉西坦治療中老年癲癇全面強直陣攣發作患者的臨床效果 [J]. 中國民康醫學, 2020, 32(5): 12+5.Liu F. Clinical efficacy of levetiracetam for middle-aged and elderly epilepsy patients with generalized tonic-clonic seizures[J]. Medical Journal of Chinese People's Health, 2020, 32(5): 12+5.
17. 羅輝, 潘鑫, 張鵬, 等. 左乙拉西坦對中老年部分性發作癲癇的療效分析[J]. 中國繼續醫學教育, 2021, 13(30): 152-156.Luo H, Pan X, Zhang P, et al. Efficacy analysis of levetiracetam in middle-aged and elderly patients with partial-onset epilepsy[J]. China Continuing Medical Education, 2021, 13(30): 152-156.
18. 陳文東. 左乙拉西坦治療中老年癲癇全面強直陣攣發作的臨床療效及其對骨密度、骨代謝的影響[J]. 臨床醫藥文獻電子雜志, 2018, 5(87): 89-90.Chen WD. Clinical efficacy of levetiracetam in treating generalized tonic-clonic seizures among middle-aged and elderly epilepsy patients and its effects on bone mineral density and bone metabolism[J]. Electronic Journal of Clinical Medical Literature, 2018, 5(87): 89-90.
19. 孫慧靜, 陳凌, 陳克龍, 等. 左乙拉西坦在中老年癲癇患者中的治療效果以及對骨代謝的影響 [J]. 中國高等醫學教育, 2017(12): 133+142.Sun HJ, Chen L, Chen KL, et al. Therapeutic effect of levetiracetam and its influence on bone metabolism in middle-aged and elderly patients with epilepsy[J]. China Higher Medical Education, 2017(12): 133+142.
20. Marson A, Burnside G, Appleton R, et al. The SANAD II study of the effectiveness and cost-effectiveness of levetiracetam, zonisamide, or lamotrigine for newly diagnosed focal epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial[J]. Lancet, 2021, 397(10282): 1363-1374.
21. Anthony Marson, Girvan Burnside, et al. The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial[J]. Lancet, 2021, 397(10282): 1375-1386.
22. Husein N, Langlois-Thérien T, Rioux B, et al. Medical and surgical treatment of epilepsy in older adults: a national survey[J]. Epilepsia, 2023, 64(4): 900-909.
23. Abou-Khalil BW. Update on Antiseizure Medications 2022[J]. Continuum (Minneap Minn), 2022, 28(2): 500-535.
24. Abou-Khalil BW. Update on Antiseizure Medications 2025[J]. Continuum (Minneap Minn), 2025, 31(1): 125-164.
25. Chen Z, Brodie MJ, Kwan P. What has been the impact of new drug treatments on epilepsy?[J]. Current Opinion in Neurology, 2020, 33(2): 185-190.
26. Zhang H, Ou Z, Zhang E, et al. Efficacy and safety of add-on antiseizure medications for focal epilepsy: a network meta-analysis[J]. Epilepsia Open, 2024, 9(4): 1550-1564.
27. Peter-Derex L, Philippeau F, Garnier P, et al. Safety and efficacy of prophylactic levetiracetam for prevention of epileptic seizures in the acute phase of intracerebral haemorrhage (PEACH): a randomised, double-blind, placebo-controlled, phase 3 trial[J]. The Lancet Neurology, 2022, 21(9): 781-791.
28. Sadeghi M, Eshraghi M, Akers KG, et al. Outcomes of status epilepticus and their predictors in the elderly—A systematic review[J]. Seizure, 2020, 81: 210-221.
29. Wolcott ZC, Freund BE, Tatum WO, et al. Antiseizure medications for primary and secondary seizure prevention after stroke[J]. Frontiers in Neurology, 2025, 16: 1648064.
30. Kawamura Y, Trinka E, Quinn TJ, et al. Pharmacological strategies for preventing post-stroke seizures and epilepsy[J]. Frontiers in Neurology, 2026, 16: 1709077.

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