All commonly used antiepileptic drugs (AEDs) have some effect on cognitive function, and the effect may be substantial when crucial functions are involved, such as learning in children, driving ability in adults, or already vulnerable functions such as memory in elderly patients. For the commonly used AEDs the effect of phenobarbitone on memory and long-term treatment with phenytoin on mental speed are well established. There is no serious impact on cognition for carbamazepine and valproate and the evidence for ethosuximide is inconclusive.
The available evidence is insufficient to support definite conclusions about the cognitive effects of five of the newer AEDs vigabatrin, zonisamide, tiagabine, gabapentin, and levetiracetam. Better evidence is available for lamotrigine, topiramate, and, to a lesser degree, oxcarbazepine. Oxcarbazepine appears not to affect cognitive function. A relatively large number of studies are available for lamotrigine, which has demonstrated a favorable cognitive profile overall, both in volunteers and in patients with epilepsy. Although dose and titration speed may be confounding factors in some of the studies of topiramate, there is clear evidence that this agent does affect cognitive function, with specific effects on attention and verbal function. For lamotrigine, attempts have been made to correlate cognitive effects with what is known of the drug's mechanism of action. This is an area of research that deserves further exploration with regard to other AEDs.
Cognitive impairment is the most common comorbid disorder in epilepsy.1,2 Memory impairments, mental slowing, and attentional deficits are the most frequently reported cognitive disorders.3,4 These consequences may be even more debilitating than the seizures; thus, it is worthwhile to explore factors leading to cognitive impairment. Although many factors may induce such cognitive impairment, we will here concentrate on the unwanted effects of antiepileptic medication on cognitive function.5
In clinical practice, most cognitive problems are multifactorial in origin and the three aforementioned factors are responsible for most cognitive problems. Moreover, the factors are related leading to therapeutic dilemmas when seizure control can only be achieved with treatment-induced cognitive side effects.
Interest in the cognitive effects of antiepileptic drug (AED) treatment is of recent origin. The possibility that cognitive impairment is a consequence or aftermath of epilepsy was raised as early as 1885 when Gowers described "epileptic dementia" as an effect of the pathological sequela of seizures. Nonetheless, the topic was not coupled to AED treatment until the 1970s,6,7 probably stimulated by the widening range of possibilities associated with the introduction of carbamazepine and valproate. A plethora of subsequent studies have been published focussing on the commonly used AEDs: valproate (VPA), carbamazepine (CBZ), and phenytoin (PHT).
Several new AEDs have been introduced in the last decade. Despite claims that newer AEDs have different efficacy profiles and are particularly efficacious in specific syndromes, head-to-head comparisons between the new AEDs and ...