Neurobehavioral effects of phenytoin prophylaxis of posttraumatic seizures

Article Abstract:

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.)

Health aspects, Wounds and injuries, Injuries

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A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures

Article Abstract:

There are approximately 420,000 head injuries each year in the United States that are serious enough to require hospitalization. A significant proportion of these patients ultimately develop seizure disorders that can last throughout life. In an attempt to reduce the rate of post-traumatic seizures, various antiepileptic drugs have been administered to these patients prophylactically after the injury. This study is an evaluation of a commonly used antiepileptic drug, phenytoin (Dilantin), for the reduction of post-traumatic seizure disorders. A group of 404 patients seen for serious head trauma were divided into two groups; one received phenytoin and the other received a placebo (an inactive substance). The study was conducted in a double-blind fashion so that neither the patient nor the treating physician knew to which group the patient belonged. Following a treatment period of one year, the patients were observed for an additional year. In the first week following treatment, 3.6 percent of the group treated with phenytoin and 14.2 percent of the patients placed in the placebo group experienced seizures. This difference between the treated and control groups was highly significant. But from day eight to the end of the first year, 21.5 percent of the phenytoin group and 15.7 percent of the placebo group had seizures. Phenytoin appears to reduce the incidence of seizure only during the immediate post-traumatic week, and apparently has no protective effects in the long-term treatment of individuals with severe head injury. (Consumer Summary produced by Reliance Medical Information, Inc.)

Methods, Traumatology

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Prevention of post-traumatic epilepsy

Article Abstract:

Over 500,000 individuals in the United States sustain significant head injuries every year. In some, the only evidence of the injury is loss of consciousness, but in approximately 15 percent of these cases the injuries are severe and the mortality rate approaches 50 percent. Of the survivors of severe head injury, approximately 10 to 15 percent experience seizures. In most cases, epilepsy is seen during the first year following the injury. Although in a 1972 survey approximately 60 percent of neurosurgeons reported they administer antiepileptic drugs following severe head trauma, studies have failed to find long-term improvement with the use of these drugs. A careful study in the August 23, 1990 issue of the New England Journal of Medicine (by Temkin and colleagues) has now documented that the beneficial effect of an antiepileptic agent (phenytoin, or Dilantin) occurs only during the first week following trauma. In a longitudinal study of more than two years duration, no beneficial effect of phenytoin therapy could be established after the initial week. As a result of this study, it appears that it may be appropriate to load the patient with injections of phenytoin during the first week following trauma, to reduce the occurrence of seizures in patients at high risk. However, continued use of phenytoin in these patients is not recommended. Other antiepileptic drugs will also need to be evaluated in long-term studies to explore their use in the prevention of post-traumatic seizure disorders. (Consumer Summary produced by Reliance Medical Information, Inc.)

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