Phenytoin versus Leviteracetam for Seizure Prophylaxis after brain injury – a meta analysis

Department of Surgery, Aga Khan University, Karachi, Pakistan.
BMC Neurology (Impact Factor: 2.49). 05/2012; 12:30. DOI: 10.1186/1471-2377-12-30
Source: PubMed

ABSTRACT Current standard therapy for seizure prophylaxis in Neuro-surgical patients involves the use of Phenytoin (PHY). However, a new drug Levetiracetam (LEV) is emerging as an alternate treatment choice. We aimed to conduct a meta-analysis to compare these two drugs in patients with brain injury.
An electronic search was performed in using Pubmed, Embase, and CENTRAL. We included studies that compared the use of LEV vs. PHY for seizure prophylaxis for brain injured patients (Traumatic brain injury, intracranial hemorrhage, intracranial neoplasms, and craniotomy). Data of all eligible studies was extracted on to a standardized abstraction sheet. Data about baseline population characteristics, type of intervention, study design and outcome was extracted. Our primary outcome was seizures.
The literature search identified 2489 unduplicated papers. Of these 2456 papers were excluded by reading the abstracts and titles. Another 25 papers were excluded after reading their complete text. We selected 8 papers which comprised of 2 RCTs and 6 observational studies. The pooled estimate's Odds Ratio 1.12 (95% CI = 0.34, 3.64) demonstrated no superiority of either drug at preventing the occurrence of early seizures. In a subset analysis of studies in which follow up for seizures lasted either 3 or 7 days, the effect estimate remained insignificant with an odds ratio of 0.96 (95% CI = 0.34, 2.76). Similarly, 2 trials reporting seizure incidence at 6 months also had insignificant pooled results while comparing drug efficacy. The pooled odds ratio was 0.96 (95% CI = 0.24, 3.79).
Levetiracetam and Phenytoin demonstrate equal efficacy in seizure prevention after brain injury. However, very few randomized controlled trials (RCTs) on the subject were found. Further evidence through a high quality RCT is highly recommended.

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    ABSTRACT: Background: Much debate exists on the optimal medication for posttraumatic seizure prophylaxis after traumatic brain injury (TBI). There is some evidence that levetiracetam (LEV) could be neuroprotective and provide long-term benefits in this patient population. Objective: The primary objective was to compare the Glasgow Outcome Scale Extended (GOS-E) 6 months or more after severe TBI. Secondary end points were presence of early seizures (0 to 7 days post-TBI) or late seizures (8 days post-TBI to phone interview), use of anticonvulsant medication when interviewed, medication-related hospital complications, and a summary of phenytoin (PHT) and LEV dosing regimens. Methods: This was an IRB-approved, single-center, prospective cohort analysis. Patients were identified by cross-referencing a list of patients receiving LEV or PHT, with a list of patients with ICD-9 code consistent with TBI. After study inclusion, patients were contacted by telephone, and the GOS-E was administered. Data for secondary end points were gathered by retrospective chart review. Results: In all, 19 patients were included in the final analysis. There was no difference in the GOS-E score assessed >= 6 months after injury (5.07 +/- 1.69 vs 5.60 +/- 2.07, P = 0.58). There was no difference in the secondary end points of early seizures (P = 0.53) or late seizures (P = 0.53). However, the PHT group experienced a higher rate of hospital days with recorded fever (0.20 +/- 0.22 vs 0 0; P = 0.014). Conclusions: Long-term functional outcome in patients who experienced a TBI was not affected by treatment with PHT or LEV; however, patients treated with PHT had a higher incidence of fever during hospitalization.
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    ABSTRACT: Although both levetiracetam and phenytoin are used for seizure prophylaxis in subdural hematomas (SDHs), there is little data on their comparative efficacies. We compared the efficacy and risk of using levetiracetam versus phenytoin for seizure prophylaxis following acute or subacute SDH diagnosis. In this retrospective cohort study, the clinical data registry at a tertiary care hospital was searched for all cases of acute or subacute SDHs that were admitted to hospital in 2002, 2003, or 2011. Risk of clinical and/or electrographic seizures, and risk of adverse drug events were compared between the two exposure arms. 124 subjects in the phenytoin arm and 164 subjects in the levetiracetam arm were included. There was no significant difference in clinical and/or electrographic seizure risk, though there was a decreased risk of adverse events in the levetiracetam arm (p < 0.001). In subjects with midline shift >0 mm, levetiracetam was associated with an increased risk of electrographic seizures during hospitalization (p = 0.028) and a decreased risk of adverse drug effects (p = 0.001), compared with phenytoin use. Levetiracetam generally appears to have a similar efficacy to phenytoin in preventing clinical and/or electrographic seizures following acute/subacute SDH diagnosis, though patients with midline shift >0 mm may have associated with a higher risk of electrographic seizures on levetiracetam compared with patients on phenytoin. Levetiracetam is associated with a lower risk of adverse drug effects. A prospective, randomized study would more definitively determine any difference in efficacy and risk between phenytoin and levetiracetam.
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