title: Pregabalin or placebo used adjunctively with levetiracetam in refractory partial-onset epilepsy: a post hoc efficacy and safety analysis in combined clinical trials.
abstract: OBJECTIVE
  Some patients with epilepsy require treatment with >1 adjunctive antiepileptic drug (AED) to achieve adequate seizure remission. The purpose of this analysis was to evaluate the efficacy and safety of adding adjunctive pregabalin to an AED regimen that included levetiracetam in patients with refractory partial-onset epilepsy.
  
  
  METHODS
  Data from the pregabalin and placebo arms of two placebo-controlled, double-blind, randomized studies of pregabalin in patients who received adjunctive treatment with levetiracetam in addition to ≥1 other AEDs were pooled for this post hoc analysis. Patients (aged ≥18 years) had ≥4 partial-onset seizures and no 28-day period free of seizures during baseline. Efficacy outcomes included Response Ratio (RRatio), change from baseline in seizure frequency, proportion of patients with ≥50% reduction in seizure frequency, and 28-day seizure-freedom rate. Safety was evaluated using adverse events (AEs).
  
  
  RESULTS
  In total, 138 patients were included in the analysis (placebo, n = 47; pregabalin, n = 91). Pregabalin was significantly better than placebo for difference in least squares mean of the RRatio (-16.4; 95% confidence interval [CI]: -28.5, -4.5; p = 0.0085), median of the difference in percentage change from baseline in seizure frequency (-22.3; 95% CI: -40.1, -7.2; p = 0.0095), and proportion of 50% responders (36.3 vs. 17.0; odds ratio, 3.2; 95% CI: 1.3, 8.3; p = 0.018), but not 28-day seizure-freedom rate (7 [7.7%] vs. 2 [4.3%]; p = 0.353). The most common AEs when adding pregabalin were dizziness/vertigo, fatigue, somnolence, blurred vision, and increased weight that were not proportional to the number of concomitant AEDs.
  
  
  CONCLUSIONS
  In this population of patients with refractory partial-onset seizures, adding pregabalin to an AED regimen with levetiracetam produced further seizure reductions. The safety profile of pregabalin in patients receiving levetiracetam and ≥1 other AEDs did not appear to be compromised by the number of concomitant AEDs.
authors.affiliation: Weill Cornell Medical College in Qatar, Qatar Foundation Education City, Doha, Qatar. bmu2001@qatar-med.cornell.edu
authors.forename: Basim M
authors.initials: BM
authors.lastname: Uthman
authors.forename: Mary
authors.initials: M
authors.lastname: Almas
authors.forename: Birol
authors.initials: B
authors.lastname: Emir
authors.forename: Suzanne
authors.initials: S
authors.lastname: Giordano
authors.forename: Teresa
authors.initials: T
authors.lastname: Leon
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004351:Drug Resistance / Q000187:drug effects; D004359:Drug Therapy, Combination / Q000009:adverse effects; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D010889:Piracetam / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010919:Placebos; D000069583:Pregabalin; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D017211:Treatment Failure; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000927:Anticonvulsants; D010919:Placebos; D000077287:Levetiracetam; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D010889:Piracetam