Antiepileptogenesis and Seizure Prevention Trials with Antiepileptic Drugs: Meta‐Analysis of Controlled Trials

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Summary:  Purpose: 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.