title: Treatment outcome after failure of a first antiepileptic drug.
abstract: OBJECTIVE
  We assessed the likelihood of 12-month seizure remission and treatment failure after failure of a first antiepileptic drug, and identified factors influencing these outcomes.
  
  
  METHODS
  SANAD (Standard and New Antiepileptic Drug) was a randomized controlled trial comparing monotherapy with standard and new antiepileptic drugs. Patients were followed up to study completion, even if they were switched from their randomized treatment. After a first treatment failure, we assessed the probability of 12-month seizure remission and treatment failure. Prognostic modeling identified predictors of these outcomes.
  
  
  RESULTS
  Forty-four percent of patients in the SANAD trial had a first treatment failure. Seventy-five percent of these subsequently achieved 12-month remission by 6 years of follow-up. Significant prognostic factors included sex, age at treatment failure, time on randomized treatment at treatment failure, neurologic insult, total number of tonic-clonic seizures at treatment failure, reason for treatment failure, seizure type, and CT/MRI scan result. After a first treatment failure, young patients without tonic-clonic seizures, with a normal CT/MRI scan and failing their treatment because of unacceptable adverse events, had the highest likelihood of 12-month remission. Approximately 50% of patients who failed a first treatment also failed their second. Significant prognostic factors included total number of tonic-clonic seizures at first treatment failure, reason for first treatment failure, and CT/MRI scan result. Patients with tonic-clonic seizures and failing because of inadequate seizure control had the highest risk of a second treatment failure.
  
  
  CONCLUSIONS
  A high proportion of patients will achieve 12-month remission after a first treatment failure. Clinical factors can stratify patients according to likely outcome.
authors.affiliation: From the Departments of Biostatistics (L.J.B., C.T.S., S.D.) and Molecular and Clinical Pharmacology (A.G.M.), University of Liverpool, UK.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bonnett
authors.affiliation: From the Departments of Biostatistics (L.J.B., C.T.S., S.D.) and Molecular and Clinical Pharmacology (A.G.M.), University of Liverpool, UK.
authors.forename: Catrin
authors.initials: C
authors.lastname: Tudur Smith
authors.affiliation: From the Departments of Biostatistics (L.J.B., C.T.S., S.D.) and Molecular and Clinical Pharmacology (A.G.M.), University of Liverpool, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Donegan
authors.affiliation: From the Departments of Biostatistics (L.J.B., C.T.S., S.D.) and Molecular and Clinical Pharmacology (A.G.M.), University of Liverpool, UK. A.G.Marson@liverpool.ac.uk.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Marson
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage*; D004827:Epilepsy / Q000175:diagnosis* / Q000188:drug therapy*; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D000077236:Topiramate; D017211:Treatment Failure; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage*; D014635:Valproic Acid / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D014635:Valproic Acid; D000077213:Lamotrigine