| Author, Year
Country
Study Design
Sample Size |
Methods |
Outcome |
| Dikmen et al. (1991)
USA
RCT
PEDro=6
NInitial=244, NFinal=124
|
Population: TBI; 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 or a placebo for 1yr post-injury. Patients were then observed for another 1yr while unmedicated.
Outcome Measure: Halstead–Reitan Neuropsychological Test Battery, Katz Adjustment Scale, Sickness Impact Profile. |
1. From 1 to 12mo, more participants in the treatment group stopped receiving their assigned drug (p<0.01) due to idiosyncratic reactions and requests.
2. 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.
3. No significant differences in neuropsychological performance were found between groups for patients with moderate injuries (GCS≥9) at 1mo or 1yr.
4. 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)
USA
RCT
|
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). The 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. |
1. 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.
2. 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).
3. 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)
USA
RCT
PEDro=6
N=244
|
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 concentration 10-20µg/ml) or placebo, starting within 24hr of injury.
Outcome Measure: Occurrence of early seizures (≤1wk of injury). |
1. 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)
USA
RCT
PEDro=6
NInitial=214, NFinal=179
|
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 were treated with phenytoin (serum concentration 10-20µg/ml) or placebo starting within 24hr of injury. Treatment duration was 18mo. Participants were switched to phenobarbital if there was a hypersensitivity to phenytoin (n=20).
Outcome Measure: Occurrence of late (>7d post-injury) seizures. |
1. 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 terms of the percentage of participants with late seizures (p=0.75). |
| McQueen et al. (1983)
United Kingdom
RCT
PEDro=7
N=164
|
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. |
1. Only 48% of the treatment group had plasma levels greater than 40µmol/l (concentrations of 40-80 µmol/l were considered therapeutic).
2. Nine percent of participants developed post-traumatic epilepsy within the first 2yr.
3. At 1yr, 6 participants in the treatment group and 5 in the control group developed post-traumatic epilepsy.
4. Eight participants in the treatment group and 7 in the control group developed seizures by 2yr. |
| Gul et al., (2019b)
Pakistan
Cohort
NInitial=163, NFinal=163 |
Population: TBI=163; IV phenytoin started within 12hr of injury, n=91; IV phenytoin started after 12hr, n=72; Mean Age= 24.69±10.186yr; Gender: Male=122, Female=41; Time Post-Injury=acute; Severity: Severe=83, Moderate=80.
Treatment: Participants with moderate to severe TBI were started on IV phenytoin at admission for seizure prophylaxis. Seizure incidence in participants given phenytoin within 12hr or after 12hr of TBI were compared. Outcomes were monitored over the first 7d of recovery.
Outcome Measure: Early seizure incidence. |
1. Patients given prophylactic IV phenytoin within 12hr of moderate to severe TBI had significantly lower incidence of seizure (p=.018) during the first 7 days compared with patients given IV phenytoin after 12hr of TBI. |
| Bhullar et al. (2014)
USA
Case Control
N=93 |
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). |
1. 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).
2. 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). |
