The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial

By A. Marson, Asya M Al-Kharusi, M. Alwaidh, R. Appleton, G. Baker, D. Chadwick, C. Cramp, O. C. Cockerell, P. Cooper, J. Doughty and 19 more. The Lancet, 2007

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Summary 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. Findings 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. Interpretation 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.

Subfields: Pediatrics, Perinatology and Child Health, Psychiatry and Mental health

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Citations in the corpus

The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial (2007, methodology): “A detailed description of the methods used for quality of life outcomes was reported to have been published in a supplementary paper (Marson et al. 2007, see 'Other Publications of Related Interest' below for bibliographic details).”
HLA-A★3101 and Carbamazepine-Induced Hypersensitivity Reactions in Europeans (2011, background): “The prevalence of carbamazepine-induced hypersensitivity that was determined in the context of the Standard and New Antiepileptic Drugs (SANAD) trial (Current Controlled Trials number, ISRCTN38354748) (also involving subjects of European descent) was 10%.(40) On the basis of this prevalence, the num”
Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes (2013, methodology): “The number of studies for each AED and their distribution by RCT class of evidence is shown in Table S1.”