Cognitive effects of lamotrigine compared with topiramate in patients with epilepsy.
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).


CONCLUSIONS
Lamotrigine had significantly less impact than topiramate on measures of cognition when used as adjunctive therapy for partial seizures.
Blum
D
D
GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709, USA. david.e.blum@gsk.com
Meador
K
K
Biton
V
V
Fakhoury
T
T
Shneker
B
B
Chung
S
S
Mills
K
K
Hammer
A
A
Isojärvi
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D003071:Cognition / Q000187:drug effects*; D004311:Double-Blind Method; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D011446:Prospective Studies; D000077236:Topiramate; D016896:Treatment Outcome; D014227:Triazines / Q000494:pharmacology* / Q000627:therapeutic use
D000927:Anticonvulsants; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D000077213:Lamotrigine