TY - JOUR
T1 - The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy
T2 - an unblinded randomised controlled trial
AU - Marson, Anthony G.
AU - Al-Kharusi, Asya M.
AU - Alwaidh, Muna
AU - Appleton, Richard
AU - Baker, Gus A.
AU - Chadwick, David W.
AU - Cramp, Celia
AU - Cockerell, Oliver C.
AU - Cooper, Paul N.
AU - Doughty, Julie
AU - Eaton, Barbara
AU - Gamble, Carrol
AU - Goulding, Peter J.
AU - Howell, Stephen JL
AU - Hughes, Adrian
AU - Jackson, Margaret
AU - Jacoby, Ann
AU - Kellett, Mark
AU - Lawson, Geoffrey R.
AU - Leach, John Paul
AU - Nicolaides, Paola
AU - Roberts, Richard
AU - Shackley, Phil
AU - Shen, Jing
AU - Smith, David F.
AU - Smith, Philip EM
AU - Smith, Catrin Tudur
AU - Vanoli, Alessandra
AU - Williamson, Paula R.
PY - 2007/3/24
Y1 - 2007/3/24
N2 - 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. Findings: 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. Interpretation: 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.
AB - 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. Findings: 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. Interpretation: 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.
UR - http://www.scopus.com/inward/record.url?scp=33947228816&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(07)60461-9
DO - 10.1016/S0140-6736(07)60461-9
M3 - Article
C2 - 17382828
AN - SCOPUS:33947228816
SN - 0140-6736
VL - 369
SP - 1016
EP - 1026
JO - Lancet
JF - Lancet
IS - 9566
ER -