Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers.
BACKGROUND
The relative cognitive and behavioral effects of lamotrigine (LTG) and topiramate (TPM) are unclear.


METHODS
The authors directly compared the cognitive and behavioral effects of LTG and TPM in 47 healthy adults using a double-blind, randomized crossover design with two 12-week treatment periods. During each treatment condition, subjects were titrated to receive either LTG or TPM at a target dose of 300 mg/day for each. Neuropsychological evaluation included 17 measures yielding 41 variables of cognitive function and subjective behavioral effects. Subjects were tested at the end of each antiepileptic drug (AED) treatment period and during two drug-free conditions (pretreatment baseline and 1 month following final AED withdrawal).


RESULTS
Direct comparison of the two AEDs revealed significantly better performance on 33 (80%) variables for LTG, but none for TPM. Even after adjustment for blood levels, performance was better on 19 (46%) variables for LTG, but none for TPM. Differences spanned both objective cognitive and subjective behavioral measures. Comparison of TPM to the non-drug average revealed significantly better performance for non-drug average on 36 (88%) variables, but none for TPM. Comparison of LTG to non-drug average revealed better performance on 7 (17%) variables for non-drug average and 4 (10%) variables for LTG.


CONCLUSIONS
Lamotrigine produces significantly fewer untoward cognitive and behavioral effects compared to topiramate (TPM) at the dosages, titrations, and timeframes employed in this study. The dosages employed may not have been equivalent in efficacy. Future studies are needed to delineate the cognitive and behavioral effects of TPM at lower dosages.
Department of Neurology, Georgetown University, Washington, DC, USA. kimford.meador@neurology.ufl.edu
K J
KJ
Meador
D W
DW
Loring
V J
VJ
Vahle
P G
PG
Ray
M A
MA
Werz
A J
AJ
Fessler
P
P
Ogrocki
M R
MR
Schoenberg
J M
JM
Miller
R P
RP
Kustra
D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003072:Cognition Disorders / Q000139:chemically induced* / Q000503:physiopathology / Q000523:psychology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000503:physiopathology / Q000523:psychology; D008875:Middle Aged; D019964:Mood Disorders / Q000139:chemically induced* / Q000503:physiopathology / Q000523:psychology; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D012016:Reference Values; D000077236:Topiramate; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage / Q000009:adverse effects*; D014705:Verbal Behavior / Q000187:drug effects
D000927:Anticonvulsants; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D000077213:Lamotrigine