The International League Against Epilepsy (ILAE) Subcommission on AED Guidelines reviewed the literature from July 2005 to March 2012 and combined results with previous analysis (2006) to provide a comprehensive update of level of AED efficacy as initial monotherapy with newly diagnosed or untreated epilepsy. Class of study (I, II, and III) and level of efficacy (A, B, C, and D) are recorded. The combined analysis (1940-2012) includes a total of 64 randomized controlled trials (RCTs) [7 with class I evidence, 2 with class II], and 11 meta-analyses.

In children with partial-onset seizures, 2 RCTs were class III because of an open-label design, too short treatment duration, and a forced exit criteria, and 4 new meta-analyses included OXC versus PHT, LTG versus CBZ, and CBZ versus OXC. CBZ is most frequently studied (n=12) followed by VPA (n=7) and PHT (n=6). OXC is the only adequate comparator for childhood partial-onset seizures and is established (level A); CBZ, PB, PHT, TPM, VPA, and VGB are possibly (level C); and clobazam (CLB), CZP, LTG, and ZNS are potentially (level D) efficacious/effective as initial monotherapy.

In children with generalized-onset tonic-clonic seizures, CBZ, PB, PHT, TPM, and VPA are possibly (level C) and OXC is potentially (level D) efficacious/effective, but there are no adequate comparators. CBZ and PHT may precipitate or aggravate generalized-onset tonic-clonic seizures (class IV suggestive evidence).

In children with absence seizures, 3 AEDs (VPA, ESM, and LTG) had new class I or class II evidence of efficacy; LEV had additional class III evidence of efficacy. ESM and VPA are adequate comparators and are established (level A); LTG is possibly (level C) effective. GBP is established as ineffective (level F); AEDs that may precipitate or aggravate absence seizures (class IV scattered reports) include CBZ, OXC, PB, PHT, TGB, and VGB. LEV failed class III placebo-controlled trial and efficacy is undetermined.

In children with BECTS, CBZ and VPA are possibly (level C) and GBP, LEV, OXC, and STM are potentially (level D) effective. For juvenile myoclonic epilepsy, TPM and VPA are potentially (level D) effective; CBZ, GBP, OXC, PHT, TGB, and VGB may precipitate or aggravate absence, myoclonic, and sometimes, generalized tonic-clonic seizures. LTG exacerbated seizures in JME (level F) in one report. [1]

COMMENT. The authors stress that their report is a working framework and not a mandatory rulebook. Multicenter studies and trial designs are needed to determine the efficacy of new AEDs compared to the old, but the most appropriate AED for a specific patient is decided by the judgment and expertise of the individual physician. Management of epilepsy remains partly an art as much as a science, especially when polytherapy is involved and overused.