CoChat
Sign Up
Cited by 976Epilepsy research and treatmentPharmacological Effects and Toxicity StudiesDiet and metabolism studies

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

Open access
Marson, Anthony G, Al-Kharusi, Asya M, Alwaidh, Muna, Appleton, Richard, Baker, Gus A, Chadwick, David W, Cramp, Celia, Cockerell, Oliver C +21 more·2007·The Lancet
DOI 10.1016/s0140-6736(07)60460-7PMC PMC2080688
Open this paper in CoChat — free account

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. 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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/s0140-6736(07)60460-7

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 29

  1. [2]Annegers JF Hauser WA Elveback LR Remission of seizures and relapse in patients with epilepsy Epilepsia 1979 20 729 37 499118
  2. [3]Cockerell OC Johnson AL Sander JW Hart YM Shorvon SD Remission of epilepsy: results from the National General Practice Study of Epilepsy Lancet 1995 346 140 44 7603228
  3. [5]French JA Kanner AM Bautista J Efficacy and tolerability of the new antiepileptic drugs i: treatment of new onset epilepsy: report of the therapeutics and technology assessment subcommittee and quality standards subcommittee of the American Academy of Neurology and the American Epilepsy Society Neurology 2004 62 1252 60 15111659
  4. [6]Marson AG Williamson PR Clough H Hutton JL Chadwick DW Carbamazepine versus valproate monotherapy for epilepsy: a meta-analysis Epilepsia 2002 43 505 13 12027911
  5. [7]Marson AG Kadir ZA Chadwick DW New antiepileptic drugs: a systematic review of their efficacy and tolerability BMJ 1996 313 1169 74 8916746 PMC2352473
  6. [8]Marson AG Hutton JL Leach JP Levetiracetam, oxcarbazepine, remacemide and zonisamide for drug resistant localization-related epilepsy: a systematic review Epilepsy Res 2001 46 259 70 11518627
  7. [9]Brodie MJ Richens A Yuen AWC Double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy. UK Lamotrigine/Carbamazepine Monotherapy Trial Group Lancet 1995 345 476 79 7710545
  8. [10]Chadwick DW Anhut H Greiner MJ A double-blind trial of gabapentin monotherapy for newly diagnosed partial seizures. International Gabapentin Monotherapy Study Group 945–77 Neurology 1998 51 1282 88 9818846
  9. [11]Dam M Ekberg R Loyning Y Waltimo O Jakobsen K A double-blind study comparing oxcarbazepine and carbamazepine in patients with newly diagnosed, previously untreated epilepsy Epilepsy Res 1989 3 70 76 2645120
  10. [12]Reunanen M Dam M Yuen AW A randomised open multicentre comparative trial of lamotrigine and carbamazepine as monotherapy in patients with newly diagnosed or recurrent epilepsy Epilepsy Res 1996 23 149 55 8964276
  11. [13]Kalviainen R Aikia M Saukkonen AM Mervaala E Riekkinen PJ Sr Vigabatrin vs carbamazepine monotherapy in patients with newly diagnosed epilepsy. A randomized, controlled study Arch Neurol 1995 52 989 96 7575227
  12. [14]Chadwick D Safety and efficacy of vigabatrin and carbamazepine in newly diagnosed epilepsy: a multicentre randomised double-blind study. Vigabatrin European Monotherapy Study Group Lancet 1999 354 13 19 10406359
  13. [15]Brodie MJ Overstall PW Giorgi L Multicentre, double-blind, randomised comparison between lamotrigine and carbamazepine in elderly patients with newly diagnosed epilepsy. The UK Lamotrigine Elderly Study Group Epilepsy Res 1999 37 81 87 10515178
  14. [17]Brodie MJ Wroe SJ Dean ADP Holdich TAH Whitehead J Stevens JW Efficacy and safety of remacemide versus carbamazepine in newly diagnosed epilepsy: comparison by sequential analysis Epilepsy Behav 2002 3 140 46 12609415
  15. [18]Chadwick DW Anhut H Greiner MJ A double-blind trial of gabapentin monotherapy for newly diagnosed partial seizures. International Gabapentin Monotherapy Study Group 945–77 Neurology 1998 51 1282 88 9818846
  16. [19]Privitera MD Brodie MJ Mattson RH Topiramate, carbamazepine and valproate monotherapy: double-blind comparison in newly diagnosed epilepsy Acta Neurol Scand 2003 107 165 75 12614309
  17. [20]Bill PA Vigonius U Pohlmann H A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in adults with previously untreated epilepsy Epilepsy Res 1997 27 195 204 9237054
  18. [21]Christe W Kramer G Vigonius U A double-blind controlled clinical trial: oxcarbazepine versus sodium valproate in adults with newly diagnosed epilepsy Epilepsy Res 1997 26 451 60 9127726
  19. [22]Guerreiro MM Vigonius U Pohlmann H A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in children and adolescents with epilepsy Epilepsy Res 1997 27 205 13 9237055
  20. [23]Steiner TJ Dellaportas CI Findley LJ Lamotrigine monotherapy in newly diagnosed untreated epilepsy: a double-blind comparison with phenytoin Epilepsia 1999 40 601 07 10386529
  21. [26]Gamble CL Williamson PR Marson AG Lamotrigine versus carbamazepine monotherapy for epilepsy Cochrane Database Syst Rev 2006 1 CD001031 16437428
  22. [28]Commission on Classification and Terminology of the International League Against Epilepsy Proposal for revised classification of epilepsies and epileptic syndromes Epilepsia 1989 30 389 99 2502382
  23. [29]Commission on Classification and Terminology of the International League Against Epilepsy Proposal for revised clinical and electroencephalographic classification of epileptic seizures Epilepsia 1981 22 489 501 6790275
  24. [31]Jones B Jarvis P Lewis JA Ebutt AF Trials to assess equivalence; the importance of rigorous methods BMJ 1996 313 36 39 8664772 PMC2351444
  25. [33]Goyden J The Silent Minority: non-respondents to sample surveys 1987 Cambridge Polity Press
  26. [34]Messenheimer JA Guberman AH Rash with lamotrigine: dosing guidelines Epilepsia 2000 41 488 10756418
  27. [35]Wong IC Mawer GE Sander JW Factors influencing the incidence of lamotrigine-related skin rash Ann Pharmacother 1999 33 1037 42 10534214
  28. [36]Rowan AJ Ramsay RE Collins JF New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine Neurology 2005 64 1868 73 15955935
  29. [37]Brodie MJ Chadwick DW Anhut H Gabapentin versus lamotrigine monotherapy: a double-blind comparison in newly diagnosed epilepsy Epilepsia 2002 43 993 1000 12199724

Cited by

Sorted by citations

Authors
Marson, A. G., Al-Kharusi, A. M., Alwaidh, M., Appleton, R., Baker, G. A., Chadwick, D. W., Cramp, C., Cockerell, O. C., Cooper, P. N., Doughty, J., Eaton, B., Gamble, C., Goulding, P. J., Howell, S. J., Hughes, A., Jackson, M., Jacoby, A., Kellett, M., Lawson, G. R., Leach, J. P., Nicolaides, P., Roberts, R., Shackley, P., Shen, J., Smith, D. F., Smith, P. E., Smith, C. T., Vanoli, A., & Williamson, P. R.
Affiliations
  • University of Liverpool (GB)
  • Southport and Formby District General Hospital (GB)
  • Whiston Hospital (GB)
  • Alder Hey Children's NHS Foundation Trust (GB)
  • Royal Shrewsbury Hospital (GB)
  • Royal London Hospital (GB)
  • Bolton NHS Foundation Trust (GB)
  • Newcastle University (GB)
  • Leeds General Infirmary (GB)
  • Royal Hallamshire Hospital (GB)
  • Arrowe Park Hospital (GB)
  • Royal Victoria Infirmary (GB)
  • Sunderland Royal Hospital (GB)
  • Southern General Hospital (GB)
  • Great Ormond Street Hospital (GB)
  • Ninewells Hospital (GB)
  • Walton Centre (GB)
Corresponding author
Marson, Anthony G
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2007-03
Volume
369
Issue
9566
Pages
1000-1015
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(07)60460-7
PMC
PMC2080688
OpenAlex
W2138521331
Cited by
976
References
0
Citations by year
2026: 23 · 2025: 38 · 2024: 31 · 2023: 31 · 2022: 44 · 2021: 49 · 2020: 73 · 2019: 44 · 2018: 52 · 2017: 62 · 2016: 48 · 2015: 45 · 2014: 54 · 2013: 49 · 2012: 79
FWCI
39.06
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Discovery Research Portal (University of Dundee) (submittedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
  • Newcastle University ePrints (Newcastle Univesity)
Funders
Health Technology Assessment Programme
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
  • Health Sciences › Medicine › Physiology › Diet and metabolism studies
Keywords
focal epilepsy, focal seizures, antiepileptic drugs, carbamazepine, lamotrigine, gabapentin, oxcarbazepine, topiramate, treatment failure, seizure remission, non-inferiority, quality of life, health economic outcomes, drug comparison, antiepileptic drug efficacy, antiepileptic drug safety
MeSH terms
Adolescent, Adult, Anticonvulsants, Child, Cost-Benefit Analysis, Epilepsies, Partial, Female, Humans, Male, Quality of Life, Treatment Outcome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review