Distinct cognitive neurophysiologic profiles for lamotrigine and topiramate.
OBJECTIVE
To contrast the effects of lamotrigine (LTG) and topiramate (TPM) on cognitive task-related and resting-state EEG and evoked potential (EP) measures.


METHODS
We used a double-blind, randomized, crossover design. Healthy adults (N = 29) had two 8-week periods of dose escalation, 4 weeks of drug maintenance (300 mg daily), and 4 weeks of washout. EEG was recorded during working memory (WM) tasks and resting conditions at baseline, at the end of each maintenance phase, and after final washout. RESULTS. LTG did not affect overt performance on the tasks, although it reduced EEG power in both resting and WM task conditions, most prominently in the 6- to 12-Hz frequency range, and attenuated P300 evoked-potential amplitude equally in both WM task loads. TPM slowed responses and increased errors. It also increased EEG power below 6 Hz in all conditions, and reduced the amplitude of a slow wave observed in a difficult version of the WM task.


CONCLUSIONS
The drugs produced both task-independent and task-related alterations in neurophysiologic measures. The EEG and EP changes produced by TPM are consistent with an impairment of WM, as evidenced by overt performance deficits on the behavioral tasks. By contrast, the reduction in synchronous cortical activity produced by LTG was not accompanied by cognitive impairment. It is unknown whether such effects would also be observed at lower doses, such as those that often are used in monotherapy for newly diagnosed patients.
Smith
Michael E
ME
San Francisco Brain Research Institute and SAM Technology, San Francisco, California 94108, USA.
Gevins
Alan
A
McEvoy
Linda K
LK
Meador
Kimford J
KJ
Ray
Patricia G
PG
Gilliam
Frank
F
D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D003072:Cognition Disorders / Q000139:chemically induced*; D003344:Cortical Synchronization / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D018913:Event-Related Potentials, P300 / Q000187:drug effects / Q000502:physiology; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced; D008875:Middle Aged; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D013647:Task Performance and Analysis; D000077236:Topiramate; D014227:Triazines / Q000009:adverse effects / Q000494:pharmacology
D000927:Anticonvulsants; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D000077213:Lamotrigine