Antiepileptic Drug-Induced Cognitive Adverse Effects

Springer Science and Business Media LLC - Tập 23 - Trang 121-137 - 2012
Marco Mula1, Michael R. Trimble2
1Department of Clinical & Experimental Medicine, Department of Neurology, Amedeo Avogadro University, Novara, Italy
2Institute of Neurology, University College London, London, England

Tóm tắt

Cognitive dysfunction is frequently observed in patients with epilepsy and represents an important challenge in the management of patients with this disorder. In this respect, the relative contribution of antiepileptic drugs (AEDs) is of relevance. The fact that a considerable number of patients require AED therapy for many years, or perhaps even a lifetime, emphasizes the need to focus on the long-term adverse effects of these drugs on cognition. The most prevalent of the CNS adverse effects observed during AED therapy are sedation, somnolence, distractibility, insomnia and dizziness. Sedation, in particular, is associated with most of the commonly used AED therapies. Nevertheless, cognitive function in individuals with epilepsy may also be influenced by several factors, of which AEDs constitute only one of many putative causes. In general terms, most studies agree that some differences exist among the older AEDs with regard to the effects on cognition, and some newer generation molecules may have a better cognitive profile than older AEDs. The mechanisms of action are an obvious determinant; however, there is still a lack of evidence for differentiation between available drugs with regard to cognitive effects. Some authors have suggested that there may be different cognitive effects associated with individual drugs; however, the question as to whether there are more specific deficits related to the action of individual drugs remains unsolved. There seems to be agreement that polytherapy and high-dose treatment can produce cognitive adverse effects and when high dosages or adjunctive polytherapy is needed, the balance between benefits and disadvantages may be negatively biased against drug treatment. Thus, drug treatment requires careful balancing in the attempt to reach maximal seizure control while avoiding neurotoxic adverse effects. Finally, the mood status of the patient and clinical relevance of the information obtained by neuropsychological testing represent important variables that need to be taken into account when discussing cognitive adverse effects of AEDs.

Tài liệu tham khảo

Brunbech L, Sabers A. Effect of antiepileptic drugs on cognitive function in individuals with epilepsy: a comparative review of newer versus older agents. Drugs 2002; 62: 593–604

Prevey ML, Delaney RC, Cramer JA, et al. Effect of valproate on cognitive functioning: comparison with carbamazepine. The Department of Veterans Affairs Epilepsy Cooperative Study 264 Group. Arch Neurol 1996; 53: 1008–16

Kalviainen R, Aikia M, Saukkonen AM, et al. Vigabatrin vs carbamazepine monotherapy in patients with newly diagnosed epilepsy: a randomized, controlled study. Arch Neurol 1995; 52: 989–96

Rogawski MA, Löscher W. The neurobiology of anti-epileptic drugs. Nat Rev Neurosci 2004; 5: 553–64

Reynolds EH, Carney MW, Toone BK. Methylation and mood. Lancet 1984; 2: 196–8

Pincus JH, Tucker GJ. Behavioral neurology. 4th ed. Oxford: Oxford University Press, 2003: 24–5

Loiseau P, Strube E, Signoret JL. Memory and epilepsy. In: Trimble MR, Reynolds EH, editors. Epilepsy, behaviour and cognitive function. New York: John Wiley & Sons, 1988: 165–77

Thompson PJ. Epilepsy and memory. In: Manelis J, Bental E, Loeber EN, et al., editors. Advances in epileptology. Vol. 17. New York: Raven Press, 1989

Aldenkamp AP, Baker GA. The neurotoxicity scale: II. Results of a patient-based scale assessing neurotoxicity in patients with epilepsy. Epilepsy Res 1997; 27: 165–73

Gray SL, Lai KV, Larson EB. Drug-induced cognition disorders in the elderly: incidence, prevention and management. Drug Saf 1999; 21: 101–22

Fliessbach K, Hoppe C, Schlegel U, et al. NeuroCogFX: a computer-based neuropsychological assessment battery for the follow-up examination of neurological patients [in German]. Fortschr Neurol Psychiatr 2006; 74: 643–50