title: The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial.
abstract: BACKGROUND
  Valproate is widely accepted as a drug of first choice for patients with generalised onset seizures, and its broad spectrum of efficacy means it is recommended for patients with seizures that are difficult to classify. Lamotrigine and topiramate are also thought to possess broad spectrum activity. The SANAD study aimed to compare the longer-term effects of these drugs in patients with generalised onset seizures or seizures that are difficult to classify.
  
  
  METHODS
  SANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm B of the study recruited 716 patients for whom valproate was considered to be standard treatment. Patients were randomly assigned to valproate, lamotrigine, or topiramate between Jan 12, 1999, and Aug 31, 2004, and follow-up data were obtained up to Jan 13, 2006. Primary outcomes were time to treatment failure, and time to 1-year remission, and analysis was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748.
  
  
  RESULTS
  For time to treatment failure, valproate was significantly better than topiramate (hazard ratio 1.57 [95% CI 1.19-2.08]), but there was no significant difference between valproate and lamotrigine (1.25 [0.94-1.68]). For patients with an idiopathic generalised epilepsy, valproate was significantly better than both lamotrigine (1.55 [1.07-2.24] and topiramate (1.89 [1.32-2.70]). For time to 12-month remission valproate was significantly better than lamotrigine overall (0.76 [0.62-0.94]), and for the subgroup with an idiopathic generalised epilepsy 0.68 (0.53-0.89). But there was no significant difference between valproate and topiramate in either the analysis overall or for the subgroup with an idiopathic generalised epilepsy.
  
  
  CONCLUSIONS
  Valproate is better tolerated than topiramate and more efficacious than lamotrigine, and should remain the drug of first choice for many patients with generalised and unclassified epilepsies. However, because of known potential adverse effects of valproate during pregnancy, the benefits for seizure control in women of childbearing years should be considered.
authors: Division of Neurological Science, University of Liverpool, UK. a.g.marson@liv.ac.uk
authors: Anthony G
authors: AG
authors: Marson
authors: Asya M
authors: AM
authors: Al-Kharusi
authors: Muna
authors: M
authors: Alwaidh
authors: Richard
authors: R
authors: Appleton
authors: Gus A
authors: GA
authors: Baker
authors: David W
authors: DW
authors: Chadwick
authors: Celia
authors: C
authors: Cramp
authors: Oliver C
authors: OC
authors: Cockerell
authors: Paul N
authors: PN
authors: Cooper
authors: Julie
authors: J
authors: Doughty
authors: Barbara
authors: B
authors: Eaton
authors: Carrol
authors: C
authors: Gamble
authors: Peter J
authors: PJ
authors: Goulding
authors: Stephen J L
authors: SJ
authors: Howell
authors: Adrian
authors: A
authors: Hughes
authors: Margaret
authors: M
authors: Jackson
authors: Ann
authors: A
authors: Jacoby
authors: Mark
authors: M
authors: Kellett
authors: Geoffrey R
authors: GR
authors: Lawson
authors: John Paul
authors: JP
authors: Leach
authors: Paola
authors: P
authors: Nicolaides
authors: Richard
authors: R
authors: Roberts
authors: Phil
authors: P
authors: Shackley
authors: Jing
authors: J
authors: Shen
authors: David F
authors: DF
authors: Smith
authors: Philip E M
authors: PE
authors: Smith
authors: Catrin Tudur
authors: CT
authors: Smith
authors: Alessandra
authors: A
authors: Vanoli
authors: Paula R
authors: PR
authors: Williamson
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003362:Cost-Benefit Analysis; D004829:Epilepsy, Generalized / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D005260:Female; D005500:Follow-Up Studies; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D019057:Quality-Adjusted Life Years; D013997:Time Factors; D000077236:Topiramate; D017211:Treatment Failure; D014227:Triazines / Q000009:adverse effects / Q000627:therapeutic use*; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D014635:Valproic Acid; D000077213:Lamotrigine