Country/Study design/PEDro Score/N
|Javed et al. (2016)
||Population: Group 1 (n=50): Mean Age=31.16yr. Group 2 (n=50): Mean Age=34.96.
Intervention: Group 1: received IV phenytoin and Levetiracetam (35 mg/kg three times daily). Group 2: EEG monitoring.
Outcome Measure: Incidence of post-traumatic seizures.
- There were no significant differences between the number patients in each group which had post-traumatic seizures.
|Khan et al. (2016)
||Population: Mean Age=24.15yr; Gender: Males=115, Females=29; Mean GCS: 59.1% (8-13), 40.9% (3-7).
Intervention: 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.
- There were no significant differences between groups in terms of the drug efficacy of Phenytoin vs Levetiracetam.
- There was no significant difference in how each drug impacted moderate vs severe TBI and seizure rates.
|Radic et al. (2014)
||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.
- There was no significant difference between LEV and PHT in clinical or electrographic seizure risk for patients without a midline shift.
- 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)
||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), occurrence of seizures, medication-related complications.
- Groups were not similar at baseline in terms of median GCS at presentation (p=0.016) and ICU discharge (p=0.044). The PHT group, compared to the LEV group, also had a longer period of time between injury and GOS-E assessment (808.8 versus 484.4d, p=0.001).
- There was no significant difference in the mean GOS-E scores at follow-up (PHT 5.07 versus LEV 5.60, p=0.58).
- There was no significant difference between groups for occurrence of early or late seizures (both p=0.53).
- Compared to the PHT group, the LEV group was significantly less likely to experience mediation-related complications (p=0.038); the PHT group had a significantly higher rate of days with fever (p=0.014).
|Inaba et al. (2013)
Prospective Controlled Trial
||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.
- There was no significant difference in seizure rates between groups (1.5% versus 1.5%, p=0.997).
- There was no significant differences between groups (LEV versus. 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)
||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.
- One patient from each group seized in the first 7d (p=0.335).
- Hospital length of stay did not differ significantly between groups (median days, LEV 26.5 versus PHT 11, p=0.134).
|Szaflarski et al. (2010)
Steinbaugh et al. (2012)
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/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.
- There were no significant differences in the occurrence of early seizures between the PHT and LEV groups (3 versus 5, p=1.0)
- There were no significant between-group differences in GOS at discharge (p=0.33) and 6mo post discharge (p=0.89).
- 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).
- 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).
- 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.
- 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 at discharge, 3 and 6mo (p=0.084) and negatively associated with GCS at discharge.
|Jones et al. (2008)
||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.
- 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.
- There was no significant difference between groups for actual seizures (p=0.556).
Dikmen et al. (2000)
||Population: TBI; Gender: Male=228, Female=51. Group 1 (n=94): Mean Age=37.14yr; Mean GCS=11.3. Group 2 (n=91): Mean Age=36.58yr; Mean GCS=11.23. Group 3 (n=94): Mean Age=35.85yr; Mean GCS=12.11.
Treatment: Patients were randomized into three groups within 24h of injury: 1) valproic acid (VPA) for 1mo then 5mo of placebo; 2) VPA for 6mo; and 3) phenytoin (PHT) for 1wk then placebo until 6mo post injury.
Outcome Measure: A battery of neuropsychological measures.
- There was a trend towards a higher mortality rate in the VPA groups compared to the PHT group (p=0.07).
- There were no significant differences at 1, 6 or 12mo on the composite measures based on all the neuropsychological measures, or on only the cognitive measures (0.551<p<0.812).
- No individual measure showed a significant difference among the treatment groups at 1, 6 or 12 months post injury.
|Temkin et al. (1999)
||Population: TBI; Gender: Male=310, Female=69. Phenytoin Group (n=132): Mean Age=36yr; Mean GCS=11.7. Valproate (1mo, n=120): Mean Age=40yr; Mean GCS=11.6. Valproate (6mo, n=127): Mean Age=36yr; Mean GCS=11.1.
Treatment: Patients were divided into three groups within 24h of injury: (1) phenytoin for 1wk (20mg/kg then 5mg/kg/d), placebo until 6mo post injury; (2) Valproate (20mg/kg, then 15mg/kg/d) for 1mo, placebo for 5mo; or (3) valproate for 6mo. Follow-up continued for 2yr.
Outcome Measure: Incidence of early and late (>7d post injury) seizures, mortality rates.
- There was no significant difference in the number of early seizures between the combined valproate (4.5%) and phenytoin (1.5%, p=0.14) groups.
- There was no significant difference between groups (p=0.19) in the occurrence of late seizures.
- Late seizures occurred in 11, 17, and 15 participants in the 1mo and 6mo valproate groups and the phenytoin group, respectively.
- There were no significant differences in mortality rates between groups (7.2% phenytoin versus 13.4% in the combined valproate group, p=0.07).
- In the phenytoin group, a participant had a rash requiring medication at 1wk and in the valproate (6mo) group a participant had low neutrophil count at 2-4wk, both thought to be treatment related.