title: Placebo-corrected efficacy of modern nonenzyme-inducing AEDs for refractory focal epilepsy: systematic review and meta-analysis.
abstract: OBJECTIVE
  Given serious concerns over the adverse effects of enzyme induction, modern nonenzyme-inducing antiepileptic drugs (AEDs) may be preferable, provided they have similar efficacy as enzyme-inducing AEDs. This is currently unclear.
  
  
  METHODS
  Therefore, we performed a meta-analysis of the evidence to determine the placebo-corrected efficacy of adjunctive treatment with modern nonenzyme-inducing AEDs versus modern enzyme-inducing AEDs that are on the market for refractory focal epilepsy.
  
  
  RESULTS
  Of 322 potentially eligible articles reviewed in full text, 129 (40%) fulfilled eligibility criteria. After excluding 92 publications, 37 studies dealing with a total of 9,860 patients with refractory focal epilepsy form the basis for the evidence. The overall weighted pooled-risk ratio (RR) in favor of enzyme-inducing AEDs over placebo was 2.37 (95% confidence interval [CI] 1.77-3.18, p < 0.001) for at least 50% seizure reduction and 4.45 (2.26-8.76, p < 0.001) for seizure freedom. The corresponding weighted pooled RR in favor of nonenzyme-inducing AEDs over placebo was 2.28 (95% CI 2.03-2.57, p < 0.001) for at least 50% seizure reduction and 3.23 (95% CI 2.23-4.67, p < 0.001) for seizure freedom. In a meta-regression analysis in the same sample with at least 50% seizure reduction as outcome, the ratio of RRs for enzyme-inducing AEDs (eight studies) versus nonenzyme-inducing AEDs (29 studies) was 1.01 (95% CI 0.77-1.34, p = 0.92)). Similarly, the ratio of RRs for a seizure-free outcome for enzyme-inducing AEDs (six studies) versus nonenzyme-inducing AEDs (19 studies) was 1.38 (95% CI 0.60-3.16, p = 0.43).
  
  
  CONCLUSIONS
  Although the presence of moderate heterogeneity may reduce the validity of the results and limit generalizations from the findings, we conclude that the efficacy of adjunctive treatment with modern nonenzyme-inducing AEDs is similar to that of enzyme-inducing AEDs. Given the negative consequences of enzyme induction, our data suggest that nonenzyme-inducing AEDs may be useful alternatives to enzyme-inducing AEDs for treatment of refractory focal epilepsy.
authors.affiliation: Department of Neurology, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg, Norway.
authors.forename: Stefan
authors.initials: S
authors.lastname: Beyenburg
authors.forename: Knut
authors.initials: K
authors.lastname: Stavem
authors.forename: Dieter
authors.initials: D
authors.lastname: Schmidt
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects*; D002986:Clinical Trials as Topic / Q000379:methods / Q000639:trends; D004351:Drug Resistance / Q000502:physiology; D004798:Enzymes / Q000187:drug effects / Q000502:physiology; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D016017:Odds Ratio; D015990:Placebo Effect; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D004798:Enzymes