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Research paper
Treatment changes in a cohort of people with apparently drug-resistant epilepsy: an extended follow-up
  1. Aidan Neligan1,
  2. Gail S Bell1,
  3. Muaz Elsayed1,
  4. Josemir W Sander1,2,
  5. Simon D Shorvon1
  1. 1Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London, UK
  2. 2SEIN-Epilepsy Institute in the Netherlands Foundation, Heemstede, The Netherlands
  1. Correspondence to Professor Simon D Shorvon, Department of Clinical & Experimental Epilepsy, UCL Institute of Neurology, Box 5, Queen Square, London WC1N 3BG, UK; s.shorvon{at}


Background The seizure response to the addition of a previously unused antiepileptic drug in a cohort of 155 people with refractory epilepsy was previously reported after a median of 18 months follow-up.

Methods The authors followed 139 (90%) of the original cohort for a median follow-up of 6.9 years to determine the longer term outcome in people with refractory epilepsy.

Results During the 6.9 year follow-up period, a total of 448 medication changes were made. Eight per cent of these resulted in 12 months or more of seizure freedom and a further 17% of changes resulted in at least 50% improvement in seizure frequency. At the last follow-up, 26 (19%) of individuals had been seizure-free for 12 months or more, and 41 (29%) had 50%–99% improvement in seizure frequency. Terminal seizure freedom was correlated with having no seizures at the time of the previous report (p=0.03), a lower number of previous antiepileptic drugs taken (p=0.052) and a lower number of concomitant antiepileptic drugs (p=0.03). In those who entered remission the probability of remaining seizure-free 5 years later was 0.48 (95% CI 0.32 to 0.63).

Discussion This suggests that about half of people with apparent drug-resistant epilepsy can have significant improvements in seizure control with further drug changes. Some will subsequently relapse, but long periods of seizure freedom or significantly improved seizure control in the absence of complete seizure control can occur. Such valuable improvements suggest that the recently proposed International League against Epilepsy definition of refractory epilepsy may be too restrictive.

  • Epilepsy
  • refractory
  • relapse
  • treatment
  • prognosis
  • epidemiology
  • anticonvulsants
  • channels
  • neurophysiology
  • neuromuscular
  • motor neuron disease
  • neuropathy

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  • Funding This work was carried out at the University College.

  • Competing interests AN has received travel grants and honoraria from Eisai, UCB and Janssen. GSB's husband works for, and has shares in, GSK. ME reports no disclosures. JWS has received research grants, honoraria or consultancy fees from various companies including UCB, Eisai, Janssen, Viropharma, Medtronic and GSK. SDS has received consultancy fees from Janssen, UCB and Eisai, and has received speaker's honoraria from GSK, Janssen and UCB. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

  • Ethics approval Approval provided by the Joint Research Ethics Committee of the National Hospital for Neurology and Neurosurgery and the UCL Institute of Neurology.

  • Provenance and peer review Not commissioned; externally peer reviewed.