Efficacy and Tolerability of the New Antiepileptic Drugs: Commentary on the Recently Published Practice Parameters

Evidence‐based Epileptology, Randomized Controlled Trials, and SANAD: A Critical Clinical View

“…This inclusiveness confounds the fundamental principles, elucidated above, about the potential for a given AED to be therapeutic for one seizure type (or syndrome or population) but deleterious for another type of epileptic seizure. It was particularly unwise to study children together with adults in this study because childrens' epilepsies, management, and response to AEDs differ significantly from adults in many respects (Panayiotopoulos et al, 2004). Women and elderly are also different subpopulations. Aim: SANAD's aim per protocol was “to compare clinicians' choice of carbamazepine (arm A) or valproate (arm B) versus appropriate comparator new drugs”—as opposed to comparing drug effects on “focal or generalized and unclassified epilepsy” as they are now reported (Marson et al, 2007a; Marson et al, 2007b).…”

“…This inclusiveness confounds the fundamental principles, elucidated above, about the potential for a given AED to be therapeutic for one seizure type (or syndrome or population) but deleterious for another type of epileptic seizure. It was particularly unwise to study children together with adults in this study because childrens' epilepsies, management, and response to AEDs differ significantly from adults in many respects (Panayiotopoulos et al, 2004). Women and elderly are also different subpopulations.…”

“…However, the issues raised here question the validity of these evidence‐based recommendations. The ILAE guidelines recognized that many influential recommendations from RCTs are incomplete (Glauser et al, 2006), may mislead physicians in the appropriate use of newer AEDs, and inadvertently perpetuate suboptimal practice in new RCTs (Panayiotopoulos et al, 2004).…”

“…Because these evidence‐based recommendations are likely to be influential in guiding prescribing practice often beyond licensed limits, their review method must be rigorous and they must be rigorous in the correct use of terminology, interpretation of the method, and the value of the component clinical trials they review. The committees responsible for making such recommendations should have adequate input from paediatric and adult clinical epileptologists on the importance of precise diagnosis (Panayiotopoulos et al, 2004). It is also within the power and the duty of such committees to ask for clarifications and incomplete reporting.…”

“…Neurology and epilepsy committees should consider issuing recommendations regarding the conduct of AED trials and resultant publications. These guidelines should insist on precise diagnostic definition of the populations studied and appropriate use of comparator AEDs so as to avoid confusion and inappropriate generalizations (Panayiotopoulos et al, 2004).…”