| Author, Year
Country
Study Design
Sample Size |
Methods |
Outcome |
| Younus et al.
(2018)
Pakistan
RCT
PEDro= 6
N = 140 |
Population: Phenytoin Group (N=69): Mean GCS=11.23. Levetiracetam group (N=73): Mean GCS=11.17. Overall: 117 males, 23 females; Mean Age=29.48±16.24y
Treatment: TBI patients admitted to the hospital were randomized into the phenytoin or levetiracetam groups. The first dose of medication was given within 24h of injury. Both groups received medication for 7 days. No statistical differences between groups at baseline
Outcomes: Abnormal EEG (EEGs were completed the 1st day post trauma and on day 7 of treatment), Seizure activity (7-10 days), Glasgow Coma Scale (GCS). |
1. The number of abnormal EEGs was found to be significantly different between the two groups (p=0.002); the levetiracetam group had fewer individuals with abnormal EEG.
2. The amount of seizure activity at follow-up was significantly different between groups (p=0.014); the levetiracetam group had fewer instances of seizures.
3. There was no significant difference between GCS scores at follow-up between the two groups. |
| Szaflarski et al. (2010)
USA
RCT
PEDro=8
N=52
Steinbaugh et al. (2012)
USA
Addition to Szaflarski et al. 2010 RCT |
Population: TBI=46; SAH=6; Phenytoin group (PHT; n=18): Mean Age=35yr; Gender: Male=13, Female=5; Mean GCS=4. Levetiracetam group (LEV; n=34): Mean Age=44yr; Gender: Male=26, Female=8; Mean GCS=5.
Treatment: Patients were randomized within 24h of injury. Patients received either a loading dose of intravenous PHT 20mg/kg, then 5mg/kg/d or intravenous LEV at 20mg/kg, and then 1000mg every 12hr for 7d.
Outcome Measure: Occurrence of early seizures, Glasgow Outcome Scale (GOS), GOS-Extended (GOSE), Disability Rating Scale (DRS), Resource Utilization Questionnaire.
Addition: Patients received continuous video EEG (cEEG) for up to 72h which was compared to the outcomes collected. |
1. There were no significant differences in the occurrence of early seizures between the PHT and LEV groups (3 versus 5, p=1.0)
2. There were no significant between-group differences in GOS at discharge (p=0.33) and 6mo post-discharge (p=0.89).
3. There were no significant differences in the occurrence of fever, increased intracranial pressure, stroke, hypotension, arrhythmia, renal/ liver abnormalities or death between the two groups (p>0.15 for all).
4. Compared to the LEV group, those in the PHT group experienced a significant worsening of their neurological status more often (p=0.024), and experienced anemia less often (p=0.076).
5. Compared to PHT group, the LEV group showed significantly lower DRS at 3 and 6mo (p=0.006 and p=0.037), and higher GOSE at 6mo (p=0.016) in patients who survived.
6. The presence of focal slowing, epileptiform discharges, and seizures were not predictive of outcome (GOS-E, DRS). More severe slowing was positively associated with DRS and negatively associated with GOS-E at discharge, 3 and 6 mo. |
| Khan et al. (2016)
Pakistan
Cohort
N=154 |
Population: TBI; Mean Age=24.15yr; Gender: Males=115, Females=29; Mean GCS: 59.1% (8-13), 40.9% (3-7).
Treatment: Group A received phenytoin (5 mg/kg/day), group B received levetiracetam (10-20 mg/kg/day).
Outcome Measure: Incidence of post-traumatic seizures, efficacy of drug on moderate vs severe TBIs. |
1. There were no significant differences between treatment groups in terms of the incidence of post-traumatic seizures.
2. There was no significant difference in how each drug impacted moderate vs severe TBI and seizure rates. |
| Javed et al. (2016)
Pakistan
Cohort
N=100 |
Population: TBI; Group 1 (n=50): Mean Age=31.16yr. Group 2 (n=50): Mean Age=34.96.
Treatment: Group 1: given IV phenytoin load then switched to enteral levetiracetam (35 mg/kg/dose three times daily) by 72h. Group 2: given IV phenytoin load then kept on phenytoin during the same time period.
Outcome Measure: Incidence of post-traumatic seizures as measured by EEG (patients with clinical seizure, mental state change or deep coma underwent EEG). |
1. There was no significant difference between the two treatment groups in terms of the number patients who had post-traumatic seizures. |
| Radic et al. (2014)
USA
Case Control
N=288 |
Population: Subdural Hematoma; Levetiracetam group (LEV; n=164): Mean Age=65.96yr; Gender: Male=98, Female=66; Mean GCS=13.5. Phenytoin group (PHT; n=124): Mean Age=62yr; Gender: Male=85, Female=39; Mean GCS=12.7.
Treatment: Patients were retrospectively analyzed. Those who received LEV were compared to those who received PHT for seizure prophylaxis.
Outcome Measure: Seizure rate and adverse drug events. |
1. There was no significant difference between LEV and PHT in clinical or electrographic seizure risk for patients without a midline shift.
2. In subjects with midline shift >0 mm, LEV 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 PHT use. |
| Gabriel & Rowe (2014)
USA
Cohort
N=19 |
Population: TBI; Phenytoin Group (PHT, n=14): Mean Age=46.8yr; Gender: Male=10, Female=4; Mean GCS=3. Levetiracetam Group (LEV, n=5): Mean Age=48.8yr; Gender: Male=3, Female=2; Mean GCS=14.
Treatment: Participants were divided based on prophylactic treatment: PHT or LEV. Follow-up interview conducted.
Outcome Measure: Glasgow Outcome Scale- Extended (GOS-E) >/= 6mos post-injury administered by telephone, occurrence of early and late seizures, medication-related complications. |
1. The LEV group had a statistically higher median GCS at presentation (p=0.016) and ICU discharge (p=0.044), compared to the PHT group. The PHT group, compared to the LEV group, had a longer period of time between injury and GOS-E assessment (808.8 versus 484.4d, p=0.001).
2. There was no significant difference in the mean GOS-E scores at follow-up (PHT 5.07 versus LEV 5.60, p=0.58).
3. There was no significant difference between groups for occurrence of early or late seizures (both p=0.53).
4. Compared to the PHT group, the LEV group was significantly less likely to experience medication-related complications (p=0.038); the PHT group had a significantly higher rate of days with fever (p=0.014). |
| Inaba et al. (2013)
USA
Prospective Controlled Trial
N=813 |
Population: TBI; Levetiracetam Group (LEV, n=406): Mean Age=51.7yr; Gender: Male=300, Female=106; Mean GCS=12.1. Phenytoin Group (PHT, n=407): Mean Age=53.6yr; Gender: Male=280, Female=127; Mean GCS=12.6.
Treatment: Participants were administered either LEV at 1000mg every 12h or PHT. In the PHT group the loading dose was 20mg/kg then 5mg/kg/d every 8h. Treatment lasted 7d.
Outcome Measure: Seizure occurrence. |
1. There was no significant difference in seizure rates between groups (1.5% versus 1.5%, p=0.997).
2. There were no significant differences between groups (LEV vs. PHT) in terms of adverse drug reactions (7.9% versus 10.3%, p=0.227), complications (28.3% versus 27.0%, p=0.679) or mortality rates (5.4% versus 3.7%, p=0.236). |
| Kruer et al. (2013)
USA
Retrospective Cohort
N=109 |
Population: TBI; Median GCS=5. Phenytoin Group (PHT, n=89): Median Age=43.1yr; Gender: Male=76, Female=13. Levetiracetam Group (LEV, n=20): Median Age=34.1yr; Gender: Male=19, Female=1.
Treatment: Retrospective review of patients administered PHT or LEV.
Outcome Measure: Occurrence of early seizures. |
1. One patient from each group seized in the first 7d (p=0.335).
2. Hospital length of stay did not differ significantly between groups (median days, LEV 26.5 versus PHT 11, p=0.134). |
| Jones et al. (2008)
USA
Cohort
N=27 |
Population: Severe TBI; Gender: Male=20, Female=7.
Treatment: Patients received levetiracetam (n=15; 500mg IV every 12h for 7d) administered within 24hr of injury and were compared to a retrospective cohort of patients who received phenytoin (n=12).
Outcome Measure: Occurrence of early seizures. |
1. There was a significant difference in the occurrence of abnormal EEG findings (seizure or seizure tendency with epileptiform activity) between groups (p= 0.003), with the levetiracetam group having more abnormal findings.
2. There was no significant difference between groups for actual seizures (p=0.556). |
