Cognitive Adverse Effects of Antiepileptic Drugs : Incidence, Mechanisms and Therapeutic Implications

Several early studies suggested that differences exist between antiepileptic drugs (AEDs) in terms of their propensity to cause adverse effects on cognitive functions, favouring carbamazepine over phenobarbital (phenobarbitone), phenytoin and valproic acid (sodium valproate). The combined results of recent studies in patients and healthy volunteers reveal that at therapeutic serum concentrations phenobarbital, phenytoin, carbamazepine, oxcarbazepine and valproic acid produce nearly comparable adverse effects on higher cognitive functions.The newer AEDs (with the exception of zonisamide and topiramate) appear to induced fewer cognitive adverse effects than the older agents. Furthermore, there is limited evidence that gabapentin, lamotrigine and vigabatrin may have beneficial effects on cognitive function. Some of the newer AEDs may also have neuroprotective effects that can prevent seizure-induced neuronal damage, and so reduce cognitive dysfunction. This is an important clinical consideration, as even modest differences between older and newer AEDs are relevant for patients.