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

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Title: The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial.
Authors: Marson AG (AUTHOR), Al-Kharusi AM (AUTHOR), Alwaidh M (AUTHOR), Appleton R (AUTHOR), Baker GA (AUTHOR), Chadwick DW (AUTHOR), Cramp C (AUTHOR), Cockerell OC (AUTHOR), Cooper PN (AUTHOR), Doughty J (AUTHOR), Eaton B (AUTHOR), Gamble C (AUTHOR), Goulding PJ (AUTHOR), Howell SJL (AUTHOR), Hughes A (AUTHOR), Jackson M (AUTHOR), Jacoby A (AUTHOR), Kellett M (AUTHOR), Lawson GR (AUTHOR), Leach JP (AUTHOR)
Source: Lancet. 3/24/2007, Vol. 369 Issue 9566, p1016-1026. 11p.
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. [ABSTRACT FROM AUTHOR]
Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial.
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  Data: <searchLink fieldCode="AR" term="%22Marson+AG%22">Marson AG</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Al-Kharusi+AM%22">Al-Kharusi AM</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Alwaidh+M%22">Alwaidh M</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Appleton+R%22">Appleton R</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Baker+GA%22">Baker GA</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chadwick+DW%22">Chadwick DW</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cramp+C%22">Cramp C</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cockerell+OC%22">Cockerell OC</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cooper+PN%22">Cooper PN</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Doughty+J%22">Doughty J</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Eaton+B%22">Eaton B</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gamble+C%22">Gamble C</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Goulding+PJ%22">Goulding PJ</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Howell+SJL%22">Howell SJL</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hughes+A%22">Hughes A</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Jackson+M%22">Jackson M</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Jacoby+A%22">Jacoby A</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kellett+M%22">Kellett M</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lawson+GR%22">Lawson GR</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Leach+JP%22">Leach JP</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Lancet%22">Lancet</searchLink>. 3/24/2007, Vol. 369 Issue 9566, p1016-1026. 11p.
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  Data: <bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Findings: </bold>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.<bold>Interpretation: </bold>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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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