Summary of trials of prophylactic antiepileptic drugs in head injury that met the inclusion criteria
| Trials | Participants | Number randomised | Intervention | Reported outcomes | Loss to follow up | Quality score |
|---|---|---|---|---|---|---|
| Glotzner et al 16 |
Head injured; had one or more listed complications; patients over 15 years of age | 151 | Carbamazepine; loading dose 100 mg ×3 per day on day 1 and 2, 200 mg ×3 per day on day 3. Maintenance dose adjusted according to serum concentrations. Loading started immediately and given for 18 months to 2 years. If oral carbamazepine could not be taken, 750 mg intravenous phenytoin on day 1 and 250-500 mg on day 2, switched to carbamazepine when oral medication was tolerated. | Early seizures, late seizures, overall mortality, persistent vegetative state | Loss to follow up over 2 years was 20% in E and 1% in C; includes drug-related withdrawal | 2[-] |
| McQueen et al 17 | Head injured; no patients with early seizures; 5 to 65 years of age | 164 | Phenytoin; loading dose 300 mg for adults; for children (< 15years), dose was calculated at 5 mg per kg body weight; dose modified according to plasma concentrations, given for 1 year. 2 year follow up. | Late seizures, overall mortality, skin rashes | Loss to follow up over 24 months was 5% | 5 |
| Young et al 19-21 |
Head injured; included all penetrating injuries and for blunt injuries, had one or more listed complications | 244 | Phenytoin; loading dose 11 mg per kg given within 24 hours. Maintenance dose modified according to plasma concentrations. Given for 18 months after injury. If hypersensitivity developed, patients were switched to phenobarbitone (n=20). 2 year follow up. | Early seizures, late seizures, overall mortality | Loss to follow up over 24 months was 26% | 3[-] |
| Temkin et al 23-25 |
Head injured; 16 years of age and older | 586 | Phenytoin; loading dose 20 mg/kg of body weight given within 24 hours; dose adjusted according to serum concentrations. Given for 1 year. 2 year follow up. | Early seizures, late seizures, overall mortality, skin rashes, neurobehavioural effects, Glasgow coma outcome score [+] | Loss to follow up over 24 months was 50% in C and 55% in E, including predrug loading withdrawals | 5 |
| Pechardre et al 26 | Head injured patients; 5 to 60 years of age | 91 | Phenytoin; loading dose 11 mg/kg given within 24 hours. Maintenance dose modified according to plasma concentrations. Given for 3 months or 1 year. 2 year follow up. | Early seizures, late seizures, overall mortality [+] | Authors report no loss to follow up | 1 |
| Manaka27 28 | Head injured patients with one or more listed complications; no age restrictions | 169 | Phenobarbitone; loading dose adjusted between 10 and 25 μg/ml started 4 weeks after head injury Full dosage for 2 years and gradually reduced over 3rd year to zero. 5 year follow up. | Late seizures to end of year 1 | Loss to follow up at 5 years was 25% | 2[-] |
| Brackett1 1-150 | Head injured adults | 125 | Phenobarbitone (60 mg) and phenytoin (200 mg) started within 12 hours following admission. Given for 18 months. 36 month follow up. | Adjusted overall seizure rates28 | Loss to follow up at 36 months was 39% | 1[-] |
| Brackett2 1-150 | Head injured adults | 49 | Phenobarbitone and phenytoin given for 6 months. Study terminated early because of low accession rates | Adjusted overall seizure rates28 | Loss to follow up at 18 months was 52% | 1[-] |
| Marshall1-150 | Head injured adults | 154 | Phenobarbitone and phenytoin. Study terminated early because drug levels unable to be kept in therapeutic range. | Adjusted overall seizure rates28 | 23% of cases lost to follow up within 48 hours | 1[-] |
| Locke1-150 | Head injured adults | 303 | Phenobarbitone or phenytoin or a combination regimen. Given for 6 months. 18 month follow up | Adjusted overall seizure rates28 | 79% of the cases died or were lost to follow up | 1[-] |
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↵1-150 = Unpublished trial; [+] = mixture of published and unpublished outcomes; [-] = quality assessment incomplete; E = experimental; C = controls.
