title: The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial.
abstract: BACKGROUND
  Carbamazepine is widely accepted as a drug of first choice for patients with partial onset seizures. Several newer drugs possess efficacy against these seizure types but previous randomised controlled trials have failed to inform a choice between these drugs. We aimed to assess efficacy with regards to longer-term outcomes, quality of life, and health economic outcomes.
  
  
  METHODS
  SANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm A recruited 1721 patients for whom carbamazepine was deemed to be standard treatment, and they were randomly assigned to receive carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Primary outcomes were time to treatment failure, and time to 12-months remission, and assessment 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, lamotrigine was significantly better than carbamazepine (hazard ratio [HR] 0.78 [95% CI 0.63-0.97]), gabapentin (0.65 [0.52-0.80]), and topiramate (0.64 [0.52-0.79]), and had a non-significant advantage compared with oxcarbazepine (1.15 [0.86-1.54]). For time to 12-month remission carbamazepine was significantly better than gabapentin (0.75 [0.63-0.90]), and estimates suggest a non-significant advantage for carbamazepine against lamotrigine (0.91 [0.77-1.09]), topiramate (0.86 [0.72-1.03]), and oxcarbazepine (0.92 [0.73-1.18]). In a per-protocol analysis, at 2 and 4 years the difference (95% CI) in the proportion achieving a 12-month remission (lamotrigine-carbamazepine) is 0 (-8 to 7) and 5 (-3 to 12), suggesting non-inferiority of lamotrigine compared with carbamazepine.
  
  
  CONCLUSIONS
  Lamotrigine is clinically better than carbamazepine, the standard drug treatment, for time to treatment failure outcomes and is therefore a cost-effective alternative for patients diagnosed with partial onset seizures.
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; D003362:Cost-Benefit Analysis; D004828:Epilepsies, Partial / Q000145:classification / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants