| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From GlaxoSmithKline, Research Triangle Park, NC (D.B., A.H., J.I.); University of Florida, Gainesville, FL (K. Meador); Arkansas Epilepsy Program, Little Rock, AR (V.B.); University of Kentucky, Lexington, KY (T.F.); Ohio State University, Columbus OH (B.S.); Barrow Neurologic Institute, Phoenix, AZ (S.C.); and Profile Associates, Chapel Hill, NC (K. Mills).
Address correspondence and reprint requests to Dr. David Blum, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709; e-mail: david.e.blum{at}gsk.com
Objective: To compare the cognitive effects of lamotrigine vs topiramate as adjunctive therapy in adults with epilepsy.
Methods: A multicenter, double-blind, randomized, prospective study was conducted in adults with partial seizures. Lamotrigine or topiramate was introduced as an adjunctive therapy to carbamazepine or phenytoin and titrated over 8 weeks to target doses. These drugs were maintained another 8 weeks (maintenance phase) without dosage changes. The primary endpoint was change from screening to the end of the maintenance phase in a combined analysis of standardized measures of cognition (Controlled Oral Word Association Task [COWA]; Stroop Color–Word Interference; Digit Cancellation; Lafayette Grooved Pegboard, dominant hand; Rey Auditory Verbal Learning Test, delayed recall; and Symbol–Digit Modalities test).
Results: For the primary endpoint, cognitive performance at the end of the maintenance phase was better with lamotrigine than with topiramate (415.3 vs 315.1; p < 0.001). On the individual cognitive tests, performance was better with lamotrigine than with topiramate in mean changes from screening on the COWA (p < 0.001), Stroop Color–Word Interference (p = 0.038), and Symbol–Digit Modalities tests (p < 0.001). The treatment effect exceeded the minimum clinically important difference for the COWA and the Symbol–Digit Modalities test. Mean changes from screening in the Performance-On-Line test simulating driving skills reflected better performance with lamotrigine than with topiramate (p = 0.021). The median percentage change from baseline in seizure frequency was lower with lamotrigine than with topiramate during the escalation phase (–80% vs –100%; p = 0.028) but not during the maintenance phase (–75% vs –100%; p = 0.062). The frequencies of cognitive adverse events and of premature withdrawals related to cognitive decline were higher with topiramate than with lamotrigine (6% vs 0%; p = 0.013).
Conclusion: Lamotrigine had significantly less impact than topiramate on measures of cognition when used as adjunctive therapy for partial seizures.
Editorial, see page 378
Disclosure: Authors Blum and Hammer are employees of GlaxoSmithKline, the sponsor of the study described in the manuscript. Author Isojärvi was employed by GlaxoSmithKline at the time the manuscript was prepared and is now employed elsewhere. By virtue of their full-time employment at GlaxoSmithKline, authors Blum, Hammer, and Isojärvi received personal compensation from the sponsor during the course of the study and had an equity interest in the sponsor of the study. They received compensation for research reported in this article as well as research and other activities not reported in this article. Authors Biton, Fakhoury, and Meador received grants from the study sponsor for research or activities not reported in this article. Authors Biton, Meador, Fakhoury, and Mills received honoraria from the study sponsor during the course of the study.
Received December 13, 2005. Accepted in final form June 5, 2006.
Related Article
Neurology 2006 67: 378-379.
This article has been cited by other articles:
|
|
 |
|
  S. F. Marasco, L. N. Sharwood, and M. J. Abramson No improvement in neurocognitive outcomes after off-pump versus on-pump coronary revascularisation: a meta-analysis Eur. J. Cardiothorac. Surg., June 1, 2008; 33(6): 961 - 970. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Meador and D. Chadwick How skeptical should we be about industry-sponsored studies? Neurology, April 10, 2007; 68(15): 1238 - 1238. [Full Text] [PDF]
|
|
|
|
|
|
D. Chadwick and M. Privitera How skeptical should we be about industry-sponsored studies? Neurology, August 8, 2006; 67(3): 378 - 379. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
