Antiepileptogenesis and Seizure Prevention Trials with Antiepileptic Drugs: Meta-Analysis of Controlled Trials
Article first published online: 20 DEC 2001
Volume 42, Issue 4, pages 515–524, April 2001
How to Cite
Temkin, N. R. (2001), Antiepileptogenesis and Seizure Prevention Trials with Antiepileptic Drugs: Meta-Analysis of Controlled Trials. Epilepsia, 42: 515–524. doi: 10.1046/j.1528-1157.2001.28900.x
- Issue published online: 20 DEC 2001
- Article first published online: 20 DEC 2001
- Accepted January 12, 2001.
- Clinical trials;
- Seizure prevention;
- Antiepileptic drugs
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.