title: Adjunctive pregabalin vs gabapentin for focal seizures: Interpretation of comparative outcomes.
abstract: OBJECTIVE
  To evaluate the comparative safety and adjunctive efficacy of pregabalin and gabapentin in reducing seizure frequency in patients with partial-onset seizures based on prestudy modeling showing superior efficacy for pregabalin.
  
  
  METHODS
  The design of this comparative efficacy and safety study of pregabalin and gabapentin as adjunctive treatment in adults with refractory partial-onset seizures was randomized, flexible dose, double blind, and parallel group. The study included a 6-week baseline and a 21-week treatment phase. The primary endpoint was the percentage change from baseline in 28-day seizure rate to the treatment phase.
  
  
  RESULTS
  A total of 484 patients were randomized to pregabalin (n = 242) or gabapentin (n = 242). Of these, 359 patients (187 pregabalin, 172 gabapentin) completed the treatment phase. The observed median and mean in percentage change from baseline was -58.65 and -47.7 (SD 48.3) for pregabalin and -57.43 and -45.28 (SD 60.6) for gabapentin. For the primary endpoint, there was no significant difference between treatments. The Hodges-Lehman estimated median difference was 0.0 (95% confidence interval -6.0 to 7.0). Safety profiles were comparable and consistent with prior trials.
  
  
  CONCLUSIONS
  The absence of the anticipated efficacy difference based on modeling of prior, nearly identical trials and the larger-than-expected response rates of the 2 antiepileptic drugs were unexpected. These findings raise questions that are potentially important to consider in future comparative efficacy trials.
  
  
  BACKGROUND
  NCT00537940.
  
  
  METHODS
  This study provides Class II evidence that for patients with partial seizures enrolled in this study, pregabalin is not superior to gabapentin in reducing seizure frequency. Because of the atypical response rates, the results of this study are poorly generalizable to other epilepsy populations.
authors: From the NYU Comprehensive Epilepsy Center (J.F., D.F.), New York, NY; Department of Psychological Medicine, Dunedin School of Medicine, University of Otago (P.G.), New Zealand; Global Product Development, Pfizer Inc. (M.A., H.B.P.), New York, NY; Yardi Epilepsy Clinic, KEM and Vatsal Hospital (N.Y.), Pune, India; and Global Product Development, Pfizer Inc. (L.K., V.P.), Groton, CT. Jacqueline.French@nyumc.org.
authors: Jacqueline
authors: J
authors: French
authors: From the NYU Comprehensive Epilepsy Center (J.F., D.F.), New York, NY; Department of Psychological Medicine, Dunedin School of Medicine, University of Otago (P.G.), New Zealand; Global Product Development, Pfizer Inc. (M.A., H.B.P.), New York, NY; Yardi Epilepsy Clinic, KEM and Vatsal Hospital (N.Y.), Pune, India; and Global Product Development, Pfizer Inc. (L.K., V.P.), Groton, CT.
authors: Paul
authors: P
authors: Glue
authors: From the NYU Comprehensive Epilepsy Center (J.F., D.F.), New York, NY; Department of Psychological Medicine, Dunedin School of Medicine, University of Otago (P.G.), New Zealand; Global Product Development, Pfizer Inc. (M.A., H.B.P.), New York, NY; Yardi Epilepsy Clinic, KEM and Vatsal Hospital (N.Y.), Pune, India; and Global Product Development, Pfizer Inc. (L.K., V.P.), Groton, CT.
authors: Daniel
authors: D
authors: Friedman
authors: From the NYU Comprehensive Epilepsy Center (J.F., D.F.), New York, NY; Department of Psychological Medicine, Dunedin School of Medicine, University of Otago (P.G.), New Zealand; Global Product Development, Pfizer Inc. (M.A., H.B.P.), New York, NY; Yardi Epilepsy Clinic, KEM and Vatsal Hospital (N.Y.), Pune, India; and Global Product Development, Pfizer Inc. (L.K., V.P.), Groton, CT.
authors: Mary
authors: M
authors: Almas
authors: From the NYU Comprehensive Epilepsy Center (J.F., D.F.), New York, NY; Department of Psychological Medicine, Dunedin School of Medicine, University of Otago (P.G.), New Zealand; Global Product Development, Pfizer Inc. (M.A., H.B.P.), New York, NY; Yardi Epilepsy Clinic, KEM and Vatsal Hospital (N.Y.), Pune, India; and Global Product Development, Pfizer Inc. (L.K., V.P.), Groton, CT.
authors: Nandan
authors: N
authors: Yardi
authors: From the NYU Comprehensive Epilepsy Center (J.F., D.F.), New York, NY; Department of Psychological Medicine, Dunedin School of Medicine, University of Otago (P.G.), New Zealand; Global Product Development, Pfizer Inc. (M.A., H.B.P.), New York, NY; Yardi Epilepsy Clinic, KEM and Vatsal Hospital (N.Y.), Pune, India; and Global Product Development, Pfizer Inc. (L.K., V.P.), Groton, CT.
authors: Lloyd
authors: L
authors: Knapp
authors: From the NYU Comprehensive Epilepsy Center (J.F., D.F.), New York, NY; Department of Psychological Medicine, Dunedin School of Medicine, University of Otago (P.G.), New Zealand; Global Product Development, Pfizer Inc. (M.A., H.B.P.), New York, NY; Yardi Epilepsy Clinic, KEM and Vatsal Hospital (N.Y.), Pune, India; and Global Product Development, Pfizer Inc. (L.K., V.P.), Groton, CT.
authors: Verne
authors: V
authors: Pitman
authors: From the NYU Comprehensive Epilepsy Center (J.F., D.F.), New York, NY; Department of Psychological Medicine, Dunedin School of Medicine, University of Otago (P.G.), New Zealand; Global Product Development, Pfizer Inc. (M.A., H.B.P.), New York, NY; Yardi Epilepsy Clinic, KEM and Vatsal Hospital (N.Y.), Pune, India; and Global Product Development, Pfizer Inc. (L.K., V.P.), Groton, CT.
authors: Holly B
authors: HB
authors: Posner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000588:Amines / Q000009:adverse effects / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D003509:Cyclohexanecarboxylic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D000069279:Drug Resistant Epilepsy / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D000077206:Gabapentin; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069583:Pregabalin / Q000009:adverse effects / Q000627:therapeutic use*; D012640:Seizures / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin