Side effect profiles and behavioral consequences of antiepileptic medications

In 1991, Dodrill carefully reviewed the behavioral effects of antiepileptic drugs (AEDs) and concluded: "The area of behavioral effects of antiepileptic drugs is poorly defined, lacks recognized and validated methods of assessment, and has suffered from a number of methodological limitations, especially including the use of experimental designs which have led to the contamination of drug effects and subject effects" (1). He further observed that the best controlled study showed that the behavioral effects of AEDs were quite limited; the benzodiazepines had the most consistently favorable effect, but were of limited utility in epilepsy, because they were not typically administered on a long-term basis; carbamazepine was associated with a favorable behavior change, but this change was seen most consistently in nonepileptic subjects; relatively few studies of valproic acid had been conducted; phenytoin was not associated with either a consistently positive or consistently negative change; and the barbiturates were clearly associated with the most negative behavior change. Since Dodrill's review, eight new AEDs have been approved by the Food and Drug Administration (FDA) for use in the United States, thereby dramatically increasing the therapeutic options for patients with epilepsy. These new drugs also increase the complexity of choosing the ideal drug for any given patient. Certainly a critical component of the decision to initiate or continue a specific treatment is the side effect profile of the medication. In clinical practice, behavioral and cognitive side effects of the older AEDs are significant concerns. This paper reviews the clinically important behavioral and cognitive side effects of the more commonly used, established AEDs as well as the newer AEDs within the limits of currently available published peer-reviewed literature and clinical experience. Particular emphasis is given to subpopulations at risk.