The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial.
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.
Marson
Anthony G
AG
Division of Neurological Science, University of Liverpool, UK. a.g.marson@liv.ac.uk
Al-Kharusi
Asya M
AM
Alwaidh
Muna
M
Appleton
Richard
R
Baker
Gus A
GA
Chadwick
David W
DW
Cramp
Celia
C
Cockerell
Oliver C
OC
Cooper
Paul N
PN
Doughty
Julie
J
Eaton
Barbara
B
Gamble
Carrol
C
Goulding
Peter J
PJ
Howell
Stephen J L
SJ
Hughes
Adrian
A
Jackson
Margaret
M
Jacoby
Ann
A
Kellett
Mark
M
Lawson
Geoffrey R
GR
Leach
John Paul
JP
Nicolaides
Paola
P
Roberts
Richard
R
Shackley
Phil
P
Shen
Jing
J
Smith
David F
DF
Smith
Philip E M
PE
Smith
Catrin Tudur
CT
Vanoli
Alessandra
A
Williamson
Paula R
PR
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
D000927:Anticonvulsants