Comprehensive Efficacy and Safety Analysis of Levetiracetam versus Phenytoin in Brain Injury: An Umbrella Review - European Medical Journal

Comprehensive Efficacy and Safety Analysis of Levetiracetam versus Phenytoin in Brain Injury: An Umbrella Review

1 Mins
Neurology
Authors:
Areeba Maryam , 1 Muhammad Hassan Waseem , 2 Muhammad Ahmad Sohail , 3 * Zain ul Abideen , 4 Brandon Lucke-Wold , 5 Syeda Nimra Qadri , 6 Esha Chaudhary , 7 Azka Shahab , 8 Sassi Abbasi , 9 FNU Deepak , 10 Aimen Zulfikar , 6 Zunaira Saeed , 6  Sania Aimen 11
  • 1. Rawalpindi Medical University, Pakistan
  • 2. Allama Iqbal Medical College, Lahore, Pakistan
  • 3. Shifa College of Medicine, Islamabad, Pakistan
  • 4. King Edward Medical University, Lahore, Pakistan
  • 5. University of Florida, USA
  • 6. Dow University of Health Sciences, Karachi, Pakistan
  • 7. Islamic International Medical College, Rawalpindi, Pakistan
  • 8. Bahria University Medical and Dental College, Karachi, Pakistan
  • 9. Sindh Institute of Urology and Transplantation, Pakistan
  • 10. Shaheed Mohtarma Benazir Bhutto Medical College, Karachi, Pakistan
  • 11. Quetta Institute of Medical Sciences, Pakistan
*Correspondence to [email protected]
Disclosure:

The authors have declared no conflicts of interest.

Citation:
Neurol AMJ. ;2[1]:37-38. https://doi.org/10.33590/neurolamj/VFNB9163.
Keywords:
Brain injury, levetiracetam, phenytoin, seizure prophylaxis, traumatic brain injury.

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.

AIMS AND OBJECTIVES

New research presented at the American Academy of Neurology (AAN) Annual Meeting 20251 reveals critical insights into the comparative efficacy and safety of levetiracetam and phenytoin for seizure prophylaxis in patients with brain injury. Traumatic brain injury is a major cause of disability worldwide, with seizures affecting a significant number of individuals. This umbrella review, synthesizing data from six systematic reviews and meta-analyses, aims to address ongoing uncertainties regarding the effectiveness of these two common anti-epileptic drugs.

METHODS AND RESULTS

A total of 14 randomized controlled trials (RCT) and 43 observational studies were included, with a focus on key outcomes, including seizure prevention, early and late seizure response, mortality, and adverse effects. The findings suggest that while levetiracetam showed a favorable safety profile, with fewer adverse effects (p=0.0003) such as nausea and hypotension, it did not significantly reduce the incidence of seizures (Figure 1) compared to phenytoin. Notably, levetiracetam was associated with a significantly higher mortality rate (p=0.04), which warrants attention in clinical practice.

Figure 1: Forest plot demonstrating the response rate of overall seizures.

Interestingly, both drugs showed similar outcomes in terms of seizure control, length of ICU and hospital stays, and early or late seizure responses. These findings highlight the need for further research to assess the precise role of levetiracetam in managing  patients with brain injury, especially given the higher mortality rate observed with its use.

CONCLUSION

The study highlights the importance of ongoing monitoring and research in refining treatment protocols and enhancing patient outcomes. It also points to the critical need for clinicians to carefully evaluate the risk-benefit profile of anti-epileptic drugs in brain injury care, considering both efficacy.

References
Maryam A et al. Comparing efficacy and safety of levetiracetam versus phenytoin in brain injury: an umbrella review. Abstract 4956. AAN Annual Meeting, 5–9 April, 2025. Xu JC et al. The safety and efficacy of levetiracetam versus phenytoin for seizure prophylaxis after traumatic brain injury: a systematic review and meta-analysis. Brain Inj. 2016;30(9):1054-61. Yang Y et al. Levetiracetam versus phenytoin for seizure prophylaxis following traumatic brain injury: a systematic review and meta-analysis. CNS Drugs. 2016;30(8):677-88. Chaari A et al. Levetiracetam versus phenytoin for seizure prophylaxis in brain injured patients: a systematic review and meta-analysis. Int J Clin Pharm. 2017;39(5):998-1003. Zhao L et al. Efficacy of levetiracetam compared with phenytoin in prevention of seizures in brain injured patients: a meta-analysis. Medicine (Baltimore). 2018;97(48):e13247.

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