Cortical excitability during prolonged antiepileptic drug treatment and drug withdrawal.
OBJECTIVE
Previous reports characterized the effects of administration of single oral doses of antiepileptic drugs (AED) on cortical excitability. However, AED effects on cortical excitability, and their relationship to plasma blood levels, during chronic drug administration at therapeutic doses are not known. The objective of the study was to determine whether plasma blood levels during chronic administration at therapeutic doses would accurately predict changes in corticomotor excitability.


METHODS
We used transcranial magnetic stimulation (TMS) to measure cortical excitability during 5 weeks administration of carbamazepine (CBZ) and lamotrigine (LTG), and subsequent AED withdrawal in 20 healthy volunteers. Data were analyzed using ANOVA(RM) and regression analysis.


RESULTS
Resting motor thresholds (r-MT) increased with increasing total and free CBZ and LTG levels during drug administration, but not drug withdrawal. After acute AED withdrawal, r-MT elevation persisted in most individuals with CBZ despite undetectable plasma levels, compared to a rapid normalization with LTG. In contrast, acute drug withdrawal resulted in a transient decrease in r-MT in 3/10 individuals with CBZ and 2/10 with LTG.


CONCLUSIONS
Plasma levels provide information on motor cortical function during active treatment phases but not during AED withdrawal.


CONCLUSIONS
The transient decrease in r-MT associated with acute AED withdrawal could represent a physiological substrate contributing to AED withdrawal seizures.
Lee
H W
HW
Clinical Epilepsy Section, National Institutes of Neurological Disorders and Stroke, Bethesda, MD, USA.
Seo
H J
HJ
Cohen
L G
LG
Bagic
A
A
Theodore
W H
WH
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000097:blood*; D002220:Carbamazepine / Q000009:adverse effects / Q000097:blood; D004558:Electric Stimulation; D019054:Evoked Potentials, Motor; D006801:Humans; D000077213:Lamotrigine; D008280:Magnetics; D009044:Motor Cortex / Q000187:drug effects*; D009433:Neural Inhibition / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D014227:Triazines / Q000009:adverse effects / Q000097:blood
D000927:Anticonvulsants; D014227:Triazines; D002220:Carbamazepine; D000077213:Lamotrigine