Cortical excitability during prolonged antiepileptic drug treatment and drug withdrawal

H. W. Lee, H. J. Seo, L. G. Cohen, A. Bagic, W. H. Theodore

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41 Scopus citations


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 ANOVARM 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. Significance: The transient decrease in r-MT associated with acute AED withdrawal could represent a physiological substrate contributing to AED withdrawal seizures.

Original languageEnglish
Pages (from-to)1105-1112
Number of pages8
JournalClinical Neurophysiology
Issue number5
StatePublished - May 2005

Bibliographical note

Funding Information:
Hyang Woon Lee was supported in part by the NINDS Competitive Postdoctoral Fellowship Award, postdoctoral program of Korea Science and Engineering Foundation (KOSEF) and Ewha Womans University Research Grant.


  • Antiepileptic drug treatment
  • Cortical excitability
  • Drug withdrawal
  • Plasma blood levels
  • Transcranial magnetic stimulation


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