A comparison of pregabalin, lamotrigine, and placebo as adjunctive therapy in patients with refractory partial-onset seizures

Baulac, Michel; Leon, Teresa; O’Brien, Terence J.; Whalen, Edward; Barrett, Jeannette

doi:10.1016/j.eplepsyres.2010.05.008

« Previous Next »Epilepsy Research
Volume 91, Issue 1 , Pages 10-19, September 2010

A comparison of pregabalin, lamotrigine, and placebo as adjunctive therapy in patients with refractory partial-onset seizures

Michel Baulac
- Hopital Pitié-Salpêtrière, APHP, Universite PARIS VI and INSERM UMR_S 975, Cortex & Epilepsy, Clinique Neurologique, Hopital de la Pitié-Salpêtrière, Paris, France
- On behalf of the A008112 Investigators, see Appendix A.
- Corresponding author at: Clinique Neurologique, Hopital de la Pitié-Salpêtrière, 47 Bld de l’Hopital, 75013 Paris, France. Tel.: +33 14 216 1811; fax: +33 14 424 5247.
Teresa Leon
- Pfizer Inc., New York, NY, United States
- On behalf of the A008112 Investigators, see Appendix A.
Terence J. O’Brien
- Department of Medicine, Royal Melbourne and Western Hospitals Melbourne, The University of Melbourne, Parkville, Victoria, Australia
- Department of Surgery, Royal Melbourne and Western Hospitals Melbourne, The University of Melbourne, Parkville, Victoria, Australia
- Department of Neurology, Royal Melbourne and Western Hospitals Melbourne, The University of Melbourne, Parkville, Victoria, Australia
- On behalf of the A008112 Investigators, see Appendix A.
Edward Whalen
- Pfizer Inc., New York, NY, United States
- On behalf of the A008112 Investigators, see Appendix A.
Jeannette Barrett
- Pfizer Inc., New York, NY, United States
- On behalf of the A008112 Investigators, see Appendix A.

Received 30 November 2009; received in revised form 5 May 2010; accepted 16 May 2010.

Summary

Purpose

This study assessed the comparative efficacy of pregabalin for refractory partial seizures.

Methods

Four-hundred and thirty-four patients with partial seizures were randomized to pregabalin, lamotrigine, or placebo as adjunctive therapy for 17 weeks of double-blind treatment. In phase I (11 weeks), pregabalin was titrated over 1 week and lamotrigine over 5 weeks to fixed dosages of 300mg/day for both. In phase II (6 weeks), patients not yet seizure-free were increased to pregabalin 600mg/day or lamotrigine 400mg/day.

Results

During phase I, there was a nonsignificant trend toward a greater reduction in seizures with pregabalin versus placebo and lamotrigine. Across the 17 weeks of treatment, pregabalin showed a median percentage reduction from baseline in seizure frequency of −20.0% (p=.001) versus placebo, and −9.7% (p=.080) versus lamotrigine. The responder rate (≥50% reduction in seizure frequency) for pregabalin exceeded that of placebo (36% vs 21%; p=.007) and lamotrigine (36% vs 24%; p=.04). Adverse events were consistent with the known safety profiles of pregabalin and lamotrigine.

Discussion

Pregabalin was demonstrated to be noninferior to lamotrigine in the treatment of refractory partial seizures. Overall conclusions were complicated by an unusually large and heterogeneous placebo response.

Keywords: Pregabalin, Lamotrigine, Placebo, Antiepileptic drugs, Randomized, Seizures