Cognitive side effects of antiepileptic drugs Pavel Ortinski a and Kimford J. Meador b, * a Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC 20007, USA b Department of Neurology, Georgetown University, Washington, DC 20007, USA Received 4 November 2003; accepted 4 November 2003 Abstract Antiepileptic drugs produce global changes in the excitation levels in the central nervous system and often lead to cognitive and behavioral deficits. These deficits vary and must be considered independently in every patient. A number of consistent risk factors have been established. Polypharmacy and high blood levels of an antiepileptic drug (AED) increase the risk of cognitive side effects. Different effects have been demonstrated for some AEDs, but comparative data are incomplete across all of them. Other factors such as patient age and type/frequency of seizures may also be important contributors to the patientÕs cognitive state. AEDs can have positive or negative effects on mood, providing another consideration in choosing the course of treatment. Ó 2003 Elsevier Inc. All rights reserved. Keywords: Antiepileptic drugs; Anticonvulsants; Cognition; Behavior 1. Introduction Antiepileptic drugs (AEDs) affect cognition by sup- pressing neuronal excitability or enhancing inhibitory neurotransmission. Cognitive side effects observed as a result of such global action are usually fairly modest in monotherapy, but can nevertheless be clinically signifi- cant. For example, epilepsy patients treated appropri- ately with AEDs in a tertiary specialty clinic displayed a highly significant worsening of perceived quality of life as a function of subtle neurotoxic symptoms despite the absence of toxic signs on neurological examination [1]. Patients treated with multiple AEDs or patients with elevated serum levels of AEDs are at increased risk of cognitive deficits. The most prevalent of the cognitive side effects observed in an AED therapy are sedation, somnolence, distractibility, insomnia, and dizziness. Sedation, in particular, is associated with most of the common AED therapies. Depressant cognitive side ef- fects are frequent in adult patients, whereas in children aggression and hyperactivity may occur. A variety of factors beyond AEDs can affect cognitive function in patients with epilepsy. As a group, epilepsy patients have been shown to perform more poorly than normal controls on a variety of cognitive measures, al- though some epilepsy patients have superior cognitive abilities [2]. The etiology of seizures is one of the primary determinants of the extent of cognitive impairment. Earlier onset of seizures, for example, frequently leads to more severe cognitive impairments. Seizure type, fre- quency, severity, and duration and cerebral lesions ac- quired before or developed as a consequence of seizures also contribute to cognitive function in epilepsy patients. 2. Old AEDs Since a great number of reviews and clinical data are available for old AEDs, we provide only a brief over- view of their cognitive effects, focusing more on the ef- fects of newer antiepileptic medications introduced in recent years. Phenytoin, carbamazepine, valproate, phenobarbital, and benzodiazepines have been used in epilepsy treatments for many years and have become established as the ‘‘traditional’’ AEDs. Their effective- ness in monotherapy and as adjuncts to other drugs, as well as their side effects, are relatively well established. Cognitive side effects associated with these drugs are moderate and can frequently be clinically significant. A * Corresponding author. Fax: 1-202-444-2661. E-mail address: kjm32@georgetown.edu (K.J. Meador). 1525-5050/$ - see front matter Ó 2003 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2003.11.008 Epilepsy & Behavior 5 (2004) S60–S65 Epilepsy & Behavior www.elsevier.com/locate/yebeh