Levetiracetam Versus Phenytoin for Seizure Prophylaxis Following Traumatic Brain Injury: A Systematic Review and Meta-Analysis
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Seizure following traumatic brain injury (TBI) constitutes a common complication that requires effective prevention to improve the outcome of TBI. Phenytoin has been the only recommended antiepileptic drug (AED) for seizure prophylaxis; however, several shortcomings have affected its use. Intravenous levetiracetam has been available since 2006 and has been increasingly accepted as a seizure prophylaxis for brain injury, mainly due to its favorable pharmacokinetic features and minimal adverse events profile. However, the efficacy and safety of levetiracetam versus phenytoin for seizure prophylaxis following TBI are not well clarified.
The aim of this study was to assess the efficacy and safety of levetiracetam versus phenytoin for seizure prophylaxis following TBI.
We conducted a search of the MEDLINE, EMBASE, and Cochrane library databases to March 2016, and screened original research that included patients with TBI who received levetiracetam. We included randomized controlled trials (RCTs) or controlled observational cohort studies that compared levetiracetam and phenytoin, as well as uncontrolled case series regarding prophylactic levetiracetam following TBI. The outcomes included early or late seizure prophylaxis and safety. The estimates of seizure prophylaxis were pooled using a meta-analysis, and the estimates for the case series were pooled using descriptive statistics.
A total of 1614 patients from 11 studies were included in this review, of whom 1285 patients from eight controlled studies (one RCT and seven cohort studies) were included in the meta-analysis. Levetiracetam was not superior to phenytoin with regard to early seizure prophylaxis (risk ratio [RR] 1.10, 95 % confidence interval [CI] 0.64–1.88); the estimate of early seizure incidence was 0.05 (95 % CI 0.02–0.08). Three studies that assessed late seizure did not indicate the superiority of levetiracetam to phenytoin. There were no differences in mortality during hospitalization or after 6 months, or in the number of patients with adverse reactions between levetiracetam and phenytoin.
Levetiracetam does not appear to be superior to phenytoin in efficacy or safety with regard to early or late seizure prophylaxis following TBI; however, no class I evidence was identified. Additional evidence from high-quality studies is required.
KeywordsTraumatic Brain Injury Glasgow Coma Scale Levetiracetam Severe Traumatic Brain Injury Ottawa Scale
Compliance with Ethical Standards
This study was supported by the National Natural Science Foundation of China (Grant Numbers 81271445 and 81501122) and the National Clinical Key Specialty Construction Foundation of China.
Conflicts of interest
Yong Yang, Fangshuo Zheng, Xin Xu and Xuefeng Wang declare that they have no conflicts of interest.
- 1.Faul M, Xu L, Wald MM, Coronado VG. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths. Atlanta: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2010.Google Scholar
- 8.Wyllie E. Wyllie’s treatment of epilepsy. 5th ed. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins; 2010.Google Scholar
- 12.Bhullar IS, Johnson D, Paul JP, Kerwin AJ, Tepas JJ 3rd, Frykberg ER. More harm than good: antiseizure prophylaxis after traumatic brain injury does not decrease seizure rates but may inhibit functional recovery. J Trauma Acute Care Surg. 2014;76(1):54–60 (discussion 60–51).CrossRefPubMedGoogle Scholar
- 13.Virant-Young D, Alexander R, Umstead G, Savoy-Moore R, Himes D, Nikolavsky M, et al. Retrospective analysis of phenytoin and levetiracetam for seizure prophylaxis after traumatic brain injury. Crit Care Med. 2009;37(12):A443.Google Scholar
- 18.Wells G, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2013. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed Nov 2013.
- 21.Carter D, Askari R, Frawley B, Rogers S. Evaluation of the use of phenytoin and levetiracetam for seizure prophylaxis in patients with traumatic brain injury. Crit Care Med. 2009;37(12):A77.Google Scholar
- 36.Young KD, Okada PJ, Sokolove PE, Palchak MJ, Panacek EA, Baren JM, et al. A randomized, double-blinded, placebo-controlled trial of phenytoin for the prevention of early posttraumatic seizures in children with moderate to severe blunt head injury. Ann Emerg Med. 2004;43(4):435–46.CrossRefPubMedGoogle Scholar
- 38.Winter ME. Phenytoin and fosphenytoin. In: Murphy JE, editor. Clinical pharmacokinetics. Bethesda: American Society of Health-System Pharmacists; 2008. p. 247–64.Google Scholar