Neurobehavioral effects of phenytoin prophylaxis of posttraumatic seizures

Seizures develop after head trauma in as many as 30,000 patients each year, while others develop cognitive or emotional impairments after such severe injuries. Because of the deleterious effects of posttraumatic seizures on patients' lives, prevention of this complication is often attempted with anticonvulsant drugs, particularly phenytoin (Dilantin). These agents, however, can themselves induce neurological impairment. Since the neurobehavioral consequences of phenytoin use by patients with head injury have not been systematically evaluated, a large, randomized study was carried out. Patients with moderate or severe head injuries who met certain criteria were randomly assigned to receive either phenytoin (208 subjects) or a placebo (inactive) drug (196 patients) for 12 months (the number of subjects per group had dropped to about 100 by one month). Subjects underwent neurobehavioral testing 1, 12, and 24 months post-injury, and received no drugs between months 12 and 24. The tests evaluated patients' cognitive abilities, psychosocial functioning, and subjective complaints. The study hypotheses held that the phenytoin group would perform more poorly at 1 and 12 months post-injury than the placebo group, but would improve between months 12 and 24 after discontinuation of the medication. Results showed that phenytoin subjects with severe head injuries did, indeed, perform more poorly than placebo subjects one month post-injury, in many cases being unable to participate in testing. No differences were seen between the groups for those with moderate injuries at the one-month point or the 12-month point. Between 12 and 24 months, phenytoin had a small adverse effect as compared with placebo. Phenytoin did not reduce the incidence of seizures, except during the first week of administration. Overall, the policies of routine use of phenytoin after head injury and of treating all injured patients, rather than only the small proportion who develop seizures, should be carefully evaluated. (Consumer Summary produced by Reliance Medical Information, Inc.)