Antiepileptogenesis and seizure prevention trials with antiepileptic drugs: meta-analysis of controlled trials.
OBJECTIVE
To synthesize evidence concerning the effect of antiepileptic drugs (AEDs) for seizure prevention and to contrast their effectiveness for provoked versus unprovoked seizures.


METHODS
Medline, Embase, and The Cochrane Clinical Trials Register were the primary sources of trials, but all trials found were included. Minimal requirements: seizure-prevention outcome given as fraction of cases; AED or control assigned by random or quasi-random mechanism. Single abstracter. Aggregate relative risk and heterogeneity evaluated using Mantel-Haenszel analyses; random effects model used if heterogeneity was significant.


RESULTS
Forty-seven trials evaluated seven drugs or combinations for preventing seizures associated with fever, alcohol, malaria, perinatal asphyxia, contrast media, tumors, craniotomy, and traumatic brain injury. Effective: Phenobarbital for recurrence of febrile seizures [relative risk (RR), 0.51; 95% confidence interval (CI), 0.32-0.82) and cerebral malaria (RR, 0.36; CI, 0.23-0.56). Diazepam for contrast media-associated seizures (RR, 0.10; CI, 0.01-0.79). Phenytoin for provoked seizures after craniotomy or traumatic brain injury (craniotomy: RR, 0.42; CI, 0.25-0.71; TBI: RR, 0.33; CI, 0.19-0.59). Carbamazepine for provoked seizures after traumatic brain injury (RR, 0.39; CI, 0.17-0.92). Lorazepam for alcohol-related seizures (RR, 0.12; CI, 0.04-0.40). More than 25% reduction ruled out valproate for unprovoked seizures after traumatic brain injury (RR, 1.28; CI, 0.76-2.16), and carbamazepine for unprovoked seizures after craniotomy (RR, 1.30; CI, 0.75-2.25).


CONCLUSIONS
Effective or promising results predominate for provoked (acute, symptomatic) seizures. For unprovoked (epileptic) seizures, no drug has been shown to be effective, and some have had a clinically important effect ruled out.
Temkin
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Department of Neurological, University of Washington, Seattle 98104-2499, USA. temkin@u.washington.edu
D000927:Anticonvulsants / Q000627:therapeutic use*; D001927:Brain Diseases / Q000150:complications; D001930:Brain Injuries / Q000150:complications; D002220:Carbamazepine / Q000627:therapeutic use; D018849:Controlled Clinical Trials as Topic / Q000706:statistics & numerical data; D003975:Diazepam / Q000627:therapeutic use; D004827:Epilepsy / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D008140:Lorazepam / Q000627:therapeutic use; D015233:Models, Statistical; D010634:Phenobarbital / Q000627:therapeutic use; D010672:Phenytoin / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012306:Risk; D012640:Seizures / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use
D000927:Anticonvulsants; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin; D008140:Lorazepam; D003975:Diazepam; D010634:Phenobarbital