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The effect of antiepileptic drugs on cognitive functions

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Impaired cognitive function is a common problem in epileptic patients. The exact cause of cognitive impairment in case of epilepsy has not been explored fully, but there is no doubt that a role in this is played by three factors: the disease underlying epilepsy; epileptic seizures proper; and negative side effects of antiepileptic drugs. Their cognitive effects are one of the major problems affecting the tolerance of therapy. The review considers the effects of phenobarbital, phenytoin, carbamazepine, valproates, oxcarbazepine, topiramate, lamotrigine, and levetiracetam in terms of their action on the cognitive function of healthy volunteers and epileptic patients.

About the Author

A. S. Kotov
M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow
Russian Federation


1. <div><p>Aldenkamp A.P., Dodson W.E., eds. Epilepsy and education; cognitive factors in learning behaviour. Epilepsia 1990;31(suppl 4): 9–20.</p><p>Dodson W.E., Pellock J.M. Pediatric Epilepsy: Diagnosis and Treatment. New York: Demos Publications, 1993.</p><p>Aldenkamp A.P., Dreifuss F.E., Renier W.O. et al. Epilepsy in Children and Adolescents. Boca Raton, FL: CRC Press, 1995.</p><p>Aldenkamp A.P. Antiepileptic drug treatment and epileptic seizures–effects on cognitive function. In: M. Trimble, B. Schmitz. (Eds). The Neuropsychiatry of Epilepsy. New York: Cambridge University Press, 2002:256–67.</p><p>Dodrill C.B., Troupin A.S. Psychotropic effects of carbamazepine in epilepsy: a double-blind comparison with phenytoin. Neurology 1977;27:1023–8.</p><p>Ideström C.M., Schalling D., Carlquist U. et al. Acute effects of diphenylhydantoin in relation to plasma levels. Behavioural and psychological studies. Psychol Med 1972;2:111–20.</p><p>Jette N.J., Marson A.G., Hutton J.L. Topiramate add-on for drug-resistant partial epilepsy. Cochrane Database Syst Rev 2002;(3):CD001417.</p><p>Marson A.G., Kadir Z.A., Hutton J.L. et al. The new antiepileptic drugs: a systematic review of their efficacy and tolerability. Epilepsia 1997;38:859–80.</p><p>Aldenkamp A.P. Cognitive and behavioural assessment in clinical trials: when should they be done? Epilepsy Res 2001;45:155–9.</p><p>Aldenkamp A.P., De Krom M., Reijs R. Newer antiepileptic drugs and cognitive issues. Epilepsia 2003;44(Suppl 4):21–9.</p><p>Vermeulen J., Aldenkamp A.P. Cognitive side-effects of chronic antiepileptic drug treatment: a review of 25 years of research. Epilepsy Res 1995;22:65–95.</p><p>MacLeod C.M., Dekaban A.S., Hunt E. Memory impairment in epileptic patients: selective effects of phenobarbital concentration. Science 1978;202:1102–4.</p><p>Calandre E.P., Dominguez-Granados R., Gomez-Rubio M. et al. Cognitive effects of long-term treatment with phenobarbital and valproic acid in school children. Acta Neur Scand 1990;81:504–6.</p><p>Gallassi R., Morreale A., Di Sarro R. et al. Cognitive effects of antiepileptic drug discontinuation. Epilepsia 1992;33(Suppl 6):41–4.</p><p>Meador K.J., Loring D.W., Huh K. et al. Comparative cognitive effects of anticonvulsants. Neurology 1990;40:391–4.</p><p>Vining E.P., Mellitis E.D., Dorsen M.M. et al. Psychologic and behavioural effects of antiepileptic drugs in children: a double-blind comparison between phenobarbital and valproic acid. Pediatrics 1987;80(2):165–74.</p><p>Meador K.J., Loring D.W., Moore E.E. et al. Comparative cognitive effects of phenobarbital, phenytoin, and valproate in healthy adults. Neurology 1995;45(8):1494–9.</p><p>Meador K.J., Loring D.W., Abney O.L. et al. Effects of carbamazepine and phenytoin on EEG and memory in healthy adults. Epilepsia 1993;34(1):153–7.</p><p>Meador K.J., Loring D.W., Allen M.E. et al. Comparative cognitive effects of carbamazepine and phenytoin in healthy adults. Neurology 1991;41:1537–40.</p><p>Smith W.L., Lowrey J.B. Effects of diphenylhydantoin on mental abilities in the elderly. J Am Geriatr Soc 1975;23:207–11.</p><p>Thompson P.J., Huppert F., Trimble M.R. Anticonvulsant drugs, cognitive function and memory. Acta Neurol Scand 1980;80:75–80.</p><p>Thompson P.J., Huppert F.A., Trimble M.R. Phenytoin and cognitive functions: effects on normal volunteers and implications for epilepsy. Br J Clin Psychol 1981;20:155–62.</p><p>Äikiä M., Kälviäinen R., Sivenius J. et al. Cognitive effects of oxcarbazepine and phenytoin monotherapy in newly diagnosed epilepsy: one year follow-up. Epilepsy Res 1992;11:199–203.</p><p>Forsythe I., Butler R., Berg I. et al. Cognitive impairment in new cases of epilepsy randomly assigned to carbamazepine, phenytoin and sodium valproate. Dev Med Child Neurol 1991;33:524–34.</p><p>Salinsky M.C., Spencer D., Oken B.S. et al. Effects of oxcarbazepine and phenytoin on the EEG and cognition in healthy volunteers. Epilepsy Behav 2004;5:894–902.</p><p>Aldenkamp A.P., Alpherts W.C.J., Blennow G. et al. Withdrawal of antiepileptic medication – effects on cognitive function in children: the Multicentre Holmfrid Study. Neurology 1993;43:41–50.</p><p>Craig I., Tallis R. Impact of valproate and phenytoin on cognitive function in elderly patients: results of a single-blind randomized comparative study. Epilepsia 1994;35:381–90.</p><p>Prevey M.L., Delaney R.C., Cramer J.A. et al. Effect of valproate on cognitive function. Comparison with carbamazepine. The Department of Veterans Affairs Epilepsy Cooperative Study 264 Group. Arch Neurol 1996;53(10):1008–16.</p><p>Thompson P.J., Trimble M.R. Sodium valproate and cognitive functioning in normal volunteers. Br J Clin Pharmacol 1981;12:819–24.</p><p>Curran H.V., Java R. Memory and psychomotor effects of oxcarbazepine in healthy human volunteers. Eur J Clin Pharmacol 1993;44:529–33.</p><p>Laaksonen R., Kaimola K., Grahn-Teräväinen E. et al. A controlled clinical trial of the effects of carbamazepine and oxcarbazepine on memory and attention [abstract]. 16th International Epilepsy Congress, Hamburg, 1985.</p><p>Sabers A., Moller A., Dam M. et al. Cognitive function and anticonvulsant therapy: effect of monotherapy in epilepsy. Acta Neurol Scand 1995;92:19–27.</p><p>McKee P.J., Blacklaw J., Forrest G. et al. A double-blind, placebo-controlled interaction study between oxcarbazepine and carbamazepine, sodium valproate and phenytoin in epileptic patients. Br J Clin Pharmacol 1994;37:27–32.</p><p>Donati F., Gobbi G., Campistol J. et al. Effects of oxcarbazepine on cognitive function in children and adolescents with partial seizures. Neurology 2006;67(4):679–82.</p><p>Privitera M., Fincham R., Penry J. et al. Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 600-, 800-, and 1000-mg daily dosages. Topiramate YE Study Group. Neurology 1996;46:1678–83.</p><p>Ketter T.A., Post R.M., Theodore W.H. Positive and negative psychiatric effects of antiepileptic drugs in patients with seizure disorders. Neurology 1999;53(Suppl 2):53–67.</p><p>Tatum W.O., French J.A., Faught E. et al. Postmarketing experience with topiramate and cognition. Epilepsia 2001;42:1134–40.</p><p>Bootsma H.P., Coolen F., Aldenkamp A.P. et al. Topiramate in clinical practice: long-term experience in patients with refractory epilepsy referred to a tertiary epilepsy center. Epilepsy Behav 2004;5(3):380–7.</p><p>Martin R., Kuzniecky R., Ho S. et al. Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults. Neurology 1999;52:321–7.</p><p>Meador K.J. Assessing cognitive effects of a new AED without the bias of practice effects [abstract]. Epilepsia 1997;38(Suppl 3):60(abst).</p><p>Aldenkamp A.P., Baker G., Mulder O.G. et al. A multicentre randomized clinical study to evaluate the effect on cognitive function of topiramate compared with valproate as add-on therapy to carbamazepine in patients with partial-onset seizures. Epilepsia 2000;41:1167–78.</p><p>Burton L.A., Harden C. Effect of topiramate on attention. Epilepsy Res 1997;27:29–32.</p><p>Thompson P.J., Baxendale S.A., Duncan J.S. et al. Effects of topiramate on cognitive function. J Neurol Neurosurg Psychiatry 2000;69:636–41.</p><p>Kockelmann E., Elger C.E., Hemstaedter C. Cognitive profile of topiramate as compared with lamotrigine in epilepsy patients on antiepileptic drug polytherapy: relationships to blood serum levels and comedication. Epilepsy Behav 2004;5:716–21.</p><p>Cohen A.F., Ashby L., Crowley D. et al. Lamotrigine (BW430C), a potential anticonvulsant. Effects on the central nervous system in comparison with phenytoin and diazepam. Br J Clin Pharmacol 1985;20:619–29.</p><p>Hamilton M.J., Cohen A.F., Yuen A.W. et al. Carbamazepine and lamotrigine in healthy volunteers: relevance to early tolerance and clinical trial dosage. Epilepsia1993;34:166–73.</p><p>Meador K.J., Loring D.W., Ray P.G. et al. Differential effects of carbamazepine and lamotrigine [abstract]. Neurology 2000;54(Suppl 3):84(abst).</p><p>Aldenkamp A.P., Arends J., Bootsma H.P. et al. Randomized, double-blind parallel-group study comparing cognitive effects of a low-dose lamotrigine with valproate and placebo in healthy volunteers. Epilepsia 2002;43:19–26.</p><p>Gillham R., Kane K., Bryant-Comstock L. et al. A double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy with health-related quality of life as an outcome measure. Seizure 2000;9:375–9.</p><p>Banks G.K., Beran R.G. Neuropsychological assessment in lamotrigine treated epileptic patients. Clin Exp Neurol 1991;28:230–7.</p><p>Smith D., Baker G., Davies G. et al. Outcomes of add-on treatment with lamotrigine in partial epilepsy. Epilepsia 1993;34:312–22.</p><p>Aldenkamp A.P., Mulder O.G., Overweg J. Cognitive effects of lamotrigine as first line add-on in patients with localized related (partial) epilepsy. J Epilepsy 1997;10:117–21.</p><p>Ettinger A.B., Weisbrot D.M., Saracco J. et al. Positive and negative psychotropic effects of lamotrigine in patients with epilepsy and mental retardation. Epilepsia 1998;39:874–7.</p><p>Earl N., McKee J.R., Sunder T.R. et al. Lamotrigine adjunctive therapy in patients with refractory epilepsy and mental retardation [abstract]. Epilepsia 2000;41(Suppl 1):72(abst).</p><p>Aarts J.H., Binnie C.D., Smit A.M. et al. Selective cognitive impairment during focal and generalized epileptiform EEG activity. Brain 1984;107:293–308.</p><p>Aldenkamp A.P., Arends J., Overweg-Plandsoen T.C. et al. Acute cognitive effects of nonconvulsive difficult-to-detect epileptic seizures and epileptiform electroencephalographic discharges. J Child Neurol 2001;16:119–23.</p><p>Binnie C.D., van Emde B.W., Kasteleijn-Nolste-Trenite D.G. et al. Acute effects of lamotrigine (BW430C) in persons with epilepsy. Epilepsia 1986;27:248–54.</p><p>Marciani M.G., Spanedda F., Bassetti M.A. et al. Effect of lamotrigine on EEG paroxysmal abnormalities and background activity: a computerized analysis. Br J Clin Pharmacol 1996;42:621–7.</p><p>Marciani M.G., Stanzione P., Mattia D. et al. Lamotrigine add-on therapy in focal epilepsy: electroencephalographic and neuropsychological evaluation. Clin Neuropharmacol 1998;21:41–7.</p><p>Mervaala E., Koivista K., Hanninen T. et al. Electrophysiological and neuropsychological profiles of lamotrigine in young and age-associated memory impairment (AAMI) subjects [abstract]. Neurology 1995;45(Suppl 4):259(abst).</p><p>Helmstaedter C., Witt J.A. Cognitive outcome of antiepileptic treatment with levetiracetam versus carbamazepine monotherapy: a non-interventional surveillance trial. Epilepsy Behav 2010;18(1–2):74–80.</p><p>Lopez-Gongora M., Martinez-Domeno A., Garcia C., Escartin A. Effect of levetiracetam on cognitive functions and quality of life: a one-year follow-up study. Epileptic Disord 2008;10(4):297–305.</p><p>Cho J.R., Koo D.L., Joo E.Y. et al. Effect of levetiracetam monotherapy on background EEG activity and cognition in drug-naïve epilepsy patients. Clin Neurophysiol 2012;123(5):883–91.</p><p>Schiemann-Delgado J., Yang H., Loge C. et al. A long-term open-label extension study assessing cognition and behaviour, tolerability, safety, and efficacy of adjunctive levetiracetam in children aged 4 to 16 years with partial-onset seizures. J Child Neurol 2012;27(1):80–9.</p><p>Meador K.J., Gevins A., Leese P.T. et al. Neurocognitive effects of brivaracetam, levetiracetam, and lorazepam. Epilepsia 2011;52(2):264–72.</p><p>Trimble M.R. Anticonvulsant drugs and cognitive function: a review of the literature. Epilepsia 1987;28(Suppl 3):37–45.</p><p>American Academy of Pediatrics. Behavioural and cognitive effects of anticonvulsant therapy. Committee on Drugs. Pediatrics 1985;76:644–7.</p></div><br />


For citations:

Kotov A.S. The effect of antiepileptic drugs on cognitive functions. Neurology, Neuropsychiatry, Psychosomatics. 2013;5(1S):45-51. (In Russ.)

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