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The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial

Lookup NU author(s): Dr Nigel Cooper, Julie Doughty, Dr Margaret Jackson, Dr Ann Jacoby, Dr Geoff Lawson, Dr Philip Shackley, Dr Jing Shen, Alessandra Vanoli

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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. 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. © 2007 Elsevier Ltd. All rights reserved.


Publication metadata

Author(s): Shen J; Shackley P; Cooper PN; Doughty J; Vanoli A; Jacoby A; Marson AG; Eaton B; Gamble C; Goulding PJ; Howell SJ; Hughes A; Jackson M; Kellett M; Lawson GR; Al-Kharusi AM; Leach JP; Nicolaides P; Roberts R; Smith DF; Smith PE; Smith CT; Williamson PR; Alwaidh M; Appleton R; Baker GA; Chadwick DW; Cramp C; Cockerell OC

Publication type: Article

Publication status: Published

Journal: Lancet

Year: 2007

Volume: 369

Issue: 9566

Pages: 1016-1026

ISSN (print): 0140-6736

ISSN (electronic): 1474-547X

Publisher: The Lancet Publishing Group

URL: http://dx.doi.org/10.1016/S0140-6736(07)60461-9

DOI: 10.1016/S0140-6736(07)60461-9


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Funding

Funder referenceFunder name
Wellcome Trust
HTA/95/13/01Department of Health
HTA_485Department of Health

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