New-onset interictal headache in Persons with epilepsy (PWE): A case–control study

Published:October 03, 2018DOI:


      • Interictal headache is a significant issue in people with epilepsy (PWE).
      • Lower seizure frequency and lower EEG abnormalities were independent predictors of interictal headache.
      • Antiepileptic drugs (AEDs) may be significant contributing factors for interictal headache.
      • Interictal headache had more of a nonmigrainous character compared with migrainous character.



      In our personal experience, headache is a frequent complaint in Persons with epilepsy (PWE) receiving antiepileptic drugs (AEDs), carbamazepine (CBZ) in particular. There is hardly any systematic study on AEDs-associated headache. We assessed the association of new-onset interictal headache in PWE with CBZ compared with other AEDs and factors associated with it.


      Two thousand PWE on AEDs were screened, and 165 persons having new-onset interictal headache were identified. Eight persons were excluded because of comorbid illnesses that could potentially contribute to a headache. Finally, 157 were recruited for the study. One hundred fifty-seven age- and sex-matched PWE on AEDs, without headache, were recruited as controls. Headache questionnaire based on the International Classification of Headache Disorders (ICHD-II) criteria was used. Demographic factors, seizure characteristics, type and dose of AEDs, findings on electroencephalogram (EEG), and magnetic resonance imaging (MRI)/computerized tomography (CT) were recorded.


      Among PWE with headache, the majority [88 (56.1%)] were on CBZ compared with other AEDs but not significantly different from controls. In 71 (45%) persons, the headache had migrainous character. In both univariate and multivariate analyses, lower seizure frequency and fewer EEG abnormalities were found to be independent predictors of headache.


      New-onset interictal headache is a significant issue in PWE; nonmigrainous headache is more common than the migrainous type. Carbamazepine was not found to have any predilection for new-onset interictal headache compared with other AEDs. A lower frequency of seizures and EEG abnormalities in PWE with headache may suggest that seizures contribute less to the development of headache and may further support the hypothesis that AEDs may be significant contributing factors for the headache.


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