|Dikmen et al. (1991)
||Population: Head Injury; Phenytoin Group (n=104): Mean Age=30.9yr; Gender: Male=82, Female=22; Median GCS=11. Placebo Group (n=101): Mean Age=32.9yr; Gender: Male=70, Female=31; Median GCS=9.
Treatment: Patients were randomized to receive phenytoin (prophylactic medication) or a placebo for 1yr. Patients were then observed for another 1yr while unmedicated.
Outcome Measure: Halstead–Reitan Neuropsychological Test Battery, Katz Adjustment Scale, Sickness Impact Profile.
- From 1 to 12mo, more participants in the treatment group stopped receiving their assigned drug (p<0.01) due to idiosyncratic reactions and requests.
- Those severely injured (GCS≤8) and receiving phenytoin did more poorly on most neuropsychological measures than controls determined by the overall rank-sum type test at 1mo (p<0.05). No significant differences were found at 1yr.
- No significant differences in neuropsychological performance were found between groups for patients with moderate injuries (GCS≥9) at 1mo or 1yr.
- Changes in neuropsychological measures from 12 to 24mo showed that phenytoin had a small but negative widespread cognitive effect as evidenced by the overall rank-sum type test (p<0.05).
|Temkin et al. (1990)
||Population: TBI; Phenytoin Group (n=208): Mean Age=34yr; Gender: Male=162, Female=46; GCS ≤10=125. Placebo Group (n=196): Mean Age=34yr; Gender: Male=147, Female=49; GCS ≤10=131.
Treatment: Participants were randomized to either the phenytoin (n=208) or placebo group (n=196). Phenytoin group received an initial dose of 20 mg/kg intravenously, then serum levels were maintained at 3–6 µmol/l. Treatment started within 24hr of injury and continued for 1yr. Follow up at 2yr.
Outcome Measure: Occurrence of early (<1wk) and late (>8d) seizures.
- Cumulative early seizure rates were 3.6% in the phenytoin group and 14.2% in the control group (p<0.001); phenytoin was associated with a decrease of 73% in the risk of early seizures.
- Late seizure occurrence (day 8 to 2yr) did not differ significantly between the treatment and control groups (27.5% vs 21.2%, p>0.2).
- More participants in the phenytoin group stopped taking the drug between day 8 and 1yr, mainly due to idiosyncratic reactions or requests (103 vs 67).
|Young et al. (1983)
||Population: TBI; Phenytoin Group (n=136): Mean Age=24.4yr; Gender: Male=110, Female=26. Placebo Group (n=108): Mean Age=25.8yr; Gender: Male=91, Female=71.
Treatment: Patients were administered phenytoin (serum concentration10-20µg/ml) or placebo, starting within 24hr of injury.
Outcome Measure: Occurrence of early seizures (≤1wk of injury).
- Five in the phenytoin group and 4 in the control group had early seizures (p=0.75).
- Mean time from injury to early seizure in the treatment and control group was 3.2 and 4.5d, respectively (p=0.41).
|Young et al. (1983)
||Population: TBI; Phenytoin Group (n=105): Mean Age=24.1yr; Gender: Male=84, Female=21. Placebo Group (n=74): Mean Age=26.3yr; Gender: Male=61, Female=13.
Treatment: Participants treated with phenytoin (serum concentration 10-20µg/ml) or placebo starting within 24hr of injury. Treated duration 18mo. Patients were switched to phenobarbital if there was a hypersensitivity to phenytoin (n=20).
Outcome Measure: Occurrence of late (>7d post injury) seizures.
- Late seizures occurred in 11 (12.9%) of the phenytoin group, 2 (10%) of the phenobarbital group, and 8 (10.8%) of controls.
- There were no significant differences between groups in the percentage of late seizures (p=0.75).
|McQueen et al. (1983)
||Population: TBI; Phenytoin Group (n=84): Gender: Male=67, Female=17; Age Range: 5-15yr=29, 16-65yr=55. Placebo Group (n=80): Gender: Male=63, Female=17; Age Range: 5-15yr=14, 16-65yr=66.
Treatment: Patients received either phenytoin or placebo for 1yr. Phenytoin administration for adults was 300mg and for children 5mg/kg. Follow-up continued for 2yr.
Outcome Measure: Occurrence of seizures.
- Only 48% of the treatment group had plasma levels greater than 40µmol/l.
- Nine percent of participants developed post-traumatic epilepsy within the first 2yr.
- At 1yr, 6 participants in the treatment group and 5 in the control group developed post-traumatic epilepsy.
- Eight participants in the treatment group and 7 in the control group developed seizures by 2yr.
|Bhullar et al. (2014)
||Population: TBI, GCS=3-8; No Prophylaxis Group (n=43): Gender: Male=28, Female=15. Phenytoin Prophylaxis Group (n=50): Gender: Male=42, Female=8.Treatment: Medical records were reviewed and patients were divided into two groups: no prophylaxis and phenytoin prophylaxis.
Outcome Measure: Occurrence of early (<7d post injury) seizures, length of stay (LOS), Glasgow Outcome Scale (GOS), modified Rankin Scale (mRS).
- There was no significant difference in the occurrence of early seizures between the no prophylaxis and phenytoin groups (2.3% versus 4.0%, p=1.0).
- The phenytoin group, compared to no prophylaxis, had longer hospital stays (36± 31 vs 25± 16d, p=0.03), and worse functional outcome at discharge (GOS, 2.9± 1.0 versus 3.4±1.1, p=0.01; mRS, 3.1± 1.5 versus 2.3±1.7, p=0.02).
|Servit & Musil (1981)
||Population: TBI; Mean Age=30.6yr; Gender: Male=128, Female=39.
Treatment: Participants in the treatment group (n=143) were administered phenytoin (160-240mg/d) and phenobarbital (20-60mg/d). The control group (n=24) was treated with conventional methods for 2yr.
Outcome Measure: Occurrence of late seizures.
- Post-traumatic epilepsy occurred in 25% of the control and 2.1% of the treatment group (p<0.001).