Skip to main content Accessibility help
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 3
  • Print publication year: 2011
  • Online publication date: October 2011

Chapter 15 - Antiepileptic drugs and cognitive disorders


Depression in epilepsy represents a frequently encountered psychiatric comorbidity that is likely to be related to a number of variables that are both biological and psychosocial. Current literature on the neurobiology of depression in epilepsy has focused on frontal lobe dysfunction. Modern studies of interictal psychiatric disorders of epilepsy have usually attempted to identify their similarities to the psychiatric disorders that meet current classificatory systems. In the interictal dysphoric disorder, eight key symptoms, grouped in three major categories, are identified: labile depressive symptoms, labile affective symptoms, and supposedly specific symptoms (paroxysmal irritability and euphoric moods). A specific instrument, named Interictal Dysphoric Disorder Inventory (IDDI), has been developed in the context of a collaborative German-Italian study. One of the most frequent methodological errors in studies of depression in epilepsy is the sole reliance on screening instruments for the diagnosis of depressive disorders.


AartsJH, BinnieCD, SmitAM, WilkinsAJ. Selective cognitive impairment during focal and generalized epileptiform EEG activity. Brain 1984;107:293–308.
ÄikiäM, KälviäinenR, SiveniusJ, et al. Cognitive effects of oxcarbazepine and phenytoin monotherapy in newly diagnosed epilepsy: one year follow-up. Epilepsy Res 1992;11:199–203.
AldenkampAP. Cognitive effects of topiramate, gabapentin and lamotrigine in healthy young adults. Neurology 2000;54:270–2.
AldenkampAP. Cognitive and behavioural assessment in clinical trials: when should they be done?Epilepsy Res 2001;45:155–9.
AldenkampAP. Antiepileptic drug treatment and epileptic seizures: effects on cognitive function. In: TrimbleM, SchmitzB, eds. The Neuropsychiatry of Epilepsy. New York: Cambridge University Press, 2002:256–67.
AldenkampAP, DodsonWE, eds. Epilepsy and education; cognitive factors in learning behavior. Epilepsia 1990;31(Suppl 4):S9–S20.
AldenkampAP, AlphertsWCJ, BlennowG, et al. Withdrawal of antiepileptic medication – effects on cognitive function in children: The Multicentre Holmfrid Study. Neurology 1993;43:41–50.
AldenkampAP, DreifussFE, RenierWO, SuumeijerPBM. Epilepsy in Children and Adolescents. Boca Raton, Fla: CRC Press, 1995.
AldenkampAP, MulderOG, OverwegJ. Cognitive effects of lamotrigine as first line add-on in patients with localized related (partial) epilepsy. J Epilepsy 1997;10:117–121.
AldenkampAP, BakerG, MulderOG, 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.
AldenkampAP, BakerG. A systematic review of the effects of lamotrigine on cognitive function and quality of life. Epilepsy Behav 2001;2:85–91.
AldenkampAP, ArendsJ, Overweg-PlandsoenTC, et al. Acute cognitive effects of nonconvulsive difficult-to-detect epileptic seizures and epileptiform electroencephalographic discharges. J Child Neurol 2001;16:119–23.
AldenkampAP, ArendsJ, BootsmaHP, 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.
AldenkampAP, De KromM, ReijsR. Newer antiepileptic drugs and cognitive issues. Epilepsia 2003;44 (Suppl 4):21–9.
AldenkampAP, AlphertsWCJ. The effect of the new antiepileptic drug rufinamide on cognitive function. Epilepsia 2006;47(7):1153–9. PubMed PMID: 16886978.
American Academy of Pediatrics. Behavioral and cognitive effects of anticonvulsant therapy. Committee on Drugs. Pediatrics 1985;76:644–7.
BanksGK, BeranRG. Neuropsychological assessment in lamotrigine treated epileptic patients. Clin Exp Neurol 1991;28:230–7.
BinnieCD, van EmdeBW, Kasteleijn-Nolste-TreniteDG, et al. Acute effects of lamotrigine (BW430C) in persons with epilepsy. Epilepsia 1986;27:248–54.
BootsmaHP, CoolenF, AldenkampAP, 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.
BurtonLA, HardenC. Effect of topiramate on attention. Epilepsy Res 1997;27:29–32.
CalandreEP, Dominguez-GranadosR, Gomez-RubioM, et al. Cognitive effects of long-term treatment with phenobarbital and valproic acid in school children. Acta Neur Scand 1990;81:504–6.
ChadwickDW, MarsonT, KadirZ. Clinical administration of new antiepileptic drugs: an overview of safety and efficacy. Epilepsia 1996;37(Suppl 6):S17–22.
CohenAF, AshbyL, CrowleyD, 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.
CraigI, TallisR. Impact of valproate and phenytoin on cognitive function in elderly patients: results of a single-blind randomized comparative study. Epilepsia 1994;35:381–90.
CurranHV, JavaR. Memory and psychomotor effects of oxcarbazepine in healthy human volunteers. Eur J Clin Pharmacol 1993;44:529–33.
DodrillCB, TroupinAS. Psychotropic effects of carbamazepine in epilepsy: a double-blind comparison with phenytoin. Neurology 1977;27:1023–28.
DodrillCB, ArnettJL, SommervilleKW, ShuV. Cognitive and quality of life effects of differing dosages of tiagabine in epilepsy. Neurology 1997;48:1025–31.
DodsonWE, PellockJM. Pediatric Epilepsy: Diagnosis and treatment. New York: Demos Publications, 1993.
DodsonWE, TrimbleMR. Epilepsy and Quality of Life. New York: Raven Press, 1994.
DonatiF, GobbiG, CampistolJ, et al. Effects of oxcarbazepine on cognitive function in children and adolescents with partial seizures. Neurology 2006;67(4):679–82.
DonatiF, GobbiG, CampistolJ, et al.; on behalf of The Oxcarbazepine Cognitive Study Group. The cognitive effects of oxcarbazepine versus carbamazepine or valproate in newly diagnosed children with partial seizures. Seizure 2007;16(8):670–9.
EarlN, McKeeJR, SunderTR, et al. Lamotrigine adjunctive therapy in patients with refractory epilepsy and mental retardation [Abstract]. Epilepsia 2000;41(Suppl 1):72.
EttingerAB, WeisbrotDM, SaraccoJ, et al. Positive and negative psychotropic effects of lamotrigine in patients with epilepsy and mental retardation. Epilepsia 1998;39:874–7.
FaughtE, WilderBJ, RamsayRE, et al. Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 200-, 400-, and 600-mg daily dosages. Neurology 1996;46:1684–90.
ForsytheI, ButlerR, BergI, 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.
FritzN, GlogauS, HoffmannJ, et al. Efficacy and cognitive side effects of tiagabine and topiramate in patients with epilepsy. Epilepsy Behav 2005;6(3):373–81.
GallassiR, MorrealeA, Di SarroR, et al. Cognitive effects of antiepileptic drug discontinuation. Epilepsia 1992;33(Suppl 6):S41–4.
GillhamR, KaneK, Bryant-ComstockL, BrodieMJ. 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.
HamiltonMJ, CohenAF, YuenAW, et al. Carbamazepine and lamotrigine in healthy volunteers: relevance to early tolerance and clinical trial dosage. Epilepsia 1993;34:166–73.
IdeströmCM, SchallingD, CarlquistU, SjoqvistF. Acute effects of diphenylhydantoin in relation to plasma levels: behavioral and psychological studies. Psychol Med 1972;2:111–20.
JetteNJ, MarsonAG, HuttonJL. Topiramate add-on for drug-resistant partial epilepsy. Cochrane Database Syst Rev 2002;(3):CD001417.
KälviäinenR, ÄikiäM, MervaalaE, et al. Long-term cognitive and EEG effects of tiagabine in drug-resistant partial epilepsy. Epilepsy Res 1996;25:291–7.
KelletMW, SmithDF, StocktonPA, ChadwickDW. Topiramate in clinical practice: first year's postlicensing experience in a specialist epilepsy clinic. J Neurol Neurosurg Psychiatry 1999;66:759–63.
KetterTA, PostRM, TheodoreWH. Positive and negative psychiatric effects of antiepileptic drugs in patients with seizure disorders. Neurology 1999;53(5 Suppl 2):53–67.
LaaksonenR, KaimolaK, Grahn-TeräväinenE, WaltimoO. A controlled clinical trial of the effects of carbamazepine and oxcarbazepine on memory and attention. 16th International Epilepsy Congress, Hamburg, 1985 (abstract).
LeachMJ, LeesG, RiddallDR. Lamotrigine: mechanisms of action. In: LevyRH, MattsonRH, MeldrumBS (eds) Antiepileptic Drugs, 4th edn. New York: Raven Press, 1995:861–9.
LeachJP, GirvanJ, PaulA, BrodieMJ. Gabapentin and cognition: a double blind, dose ranging, placebo controlled study in refractory epilepsy. J Neurol Neurosurg Psychiatry 1997;62:372–6.
LhatooSD, WongICK, SanderJW. Prognostic factors affecting long-term retention of topiramate in patients with chronic epilepsy. Epilepsia 2000;41:338–41.
MacdonaldRL, KellyKM. Antiepileptic drug mechanisms of action. Epilepsia 1995;36(S2):2–12.
MacLeodCM, DekabanAS, HuntE. Memory impairment in epileptic patients: selective effects of phenobarbital concentration. Science 1978;202:1102–4.
MarcianiMG, SpaneddaF, BassettiMA, et al. Effect of lamotrigine on EEG paroxysmal abnormalities and background activity: a computerized analysis. Br J Clin Pharmacol 1996;42:621–7.
MarcianiMG, StanzioneP, MattiaD, et al. Lamotrigine add-on therapy in focal epilepsy: electroencephalographic and neuropsychological evaluation. Clin Neuropharmacol 1998;21:41–7.
MarsonAG, KadirZA, HuttonJL, ChadwickDW. The new antiepileptic drugs: a systematic review of their efficacy and tolerability. Epilepsia 1997;38:859–80.
MarsonAG, KadirZA, HuttonJL, ChadwickDW. Gabapentin for drug-resistant partial epilepsy. Cochrane Database Syst Rev 2000;(2):CD001415.
MarsonAG, HuttonJL, LeachJP, et al. Levetiracetam, oxcarbazepine, remacemide and zonisamide for drug resistant localization-related epilepsy: a systematic review. Epilepsy Res 2001;46:259–70.
MartinR, KuznieckyR, HoS, et al. Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults. Neurology 1999;52:321–7.
McKeePJ, BlacklawJ, ForrestG, 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.
MeadorKJ. Assessing cognitive effects of a new AED without the bias of practice effects [Abstract]. Epilepsia 1997;38(Suppl 3):60.
MeadorKJM, LoringDW, HuhK, et al. Comparative cognitive effects of anticonvulsants. Neurology 1990;40:391–4.
MeadorKJM, LoringDW, AllenME, et al. Comparative cognitive effects of carbamazepine and phenytoin in healthy adults. Neurology 1991;41:1537–40.
MeadorKJM, LoringDW, AbneyOL, et al. Effects of carbamazepine and phenytoin on EEG and memory in healthy adults. Epilepsia 1993;34(1):153–7.
MeadorKJ, LoringDW, RayPG, et al. Differential cognitive effects of carbamazepine and gabapentin. Epilepsia 1999;40:1279–85.
MeadorKJ, LoringDW, RayPG, et al. Differential effects of carbamazepine and lamotrigine [Abstract]. Neurology 2000;54(Suppl 3):A84.
MervaalaE, KoivistaK, HanninenT, et al. Electrophysiological and neuropsychological profiles of lamotrigine in young and age-associated memory impairment (AAMI) subjects [Abstract]. Neurology 1995;45(Suppl 4):A259.
MortimoreC, TrimbleM, EmmersE. Effects of gabapentin on cognition and quality of life in patients with epilepsy. Seizure 1998;7:359–6.
NeyensLGJ, AlphertsWCJ, AldenkampAP. Cognitive effects of a new pyrrolidine derivative (levetiracetam) in patients with epilepsy. Prog Neuropsychopharmacol Biol Psychiatry 1995;19:411–9.
PetroffOAC, RothmanDL, BeharKL, et al. The effect of gabapentin on brain gamma-aminobutyric acid in patients with epilepsy. Ann Neurol 1996;39:95–9.
PreveyML, DelaneyRC, CramerJA, 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.
PriviteraM, FinchamR, PenryJ, 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.
SabersA, MollerA, DamM, et al. Cognitive function and anticonvulsant therapy: effect of monotherapy in epilepsy. Acta Neurol Scand 1995;92:19–27.
SchwarzJR, GrigatG. Phenytoin and carbamazepine: potential- and frequency-dependent block of NA currents in mammalian myelinated nerve fibers. Epilepsia 1989;30:286–94.
SmithD, BakerG, DaviesG, et al. Outcomes of add-on treatment with lamotrigine in partial epilepsy. Epilepsia 1993;34:312–22.
SmithWL, LowreyJB. Effects of diphenylhydantoin on mental abilities in the elderly. J Am Geriatr Soc 1975;23:207–11.
StefanH, KrämerG, MamoliB, eds. Challenge Epilepsy – New Antiepileptic Drugs. Berlin: Blackwell Science, 1998.
SveinbjornsdottirS, SanderJW, PatsalosPN, et al. Neuropsychological effects of tiagabine, a potential new antiepileptic drug. Seizure 1994;3:29–35.
TatumWO, FrenchJA, FaughtE, et al. Postmarketing experience with topiramate and cognition. Epilepsia 2001;42:1134–40.
ThompsonPJ, TrimbleMR. Sodium valproate in cognitive functioning in normal volunteers. Br J Clin Pharmacol 1981;12:819–24.
ThompsonPJ, HuppertF, TrimbleMR. Anticonvulsant drugs, cognitive function and memory. Acta Neurol Scand 1980;S80:75–80.
ThompsonPJ, HuppertFA, TrimbleMR. Phenytoin and cognitive functions: effects on normal volunteers and implications for epilepsy. Br J Clin Psychol 1981;20:155–62.
ThompsonPJ, BaxendaleSA, DuncanJS, SanderJW. Effects of topiramate on cognitive function. J Neurol Neurosurg Psychiatry 2000;69:636–41.
TrimbleMR. Anticonvulsant drugs and cognitive function: a review of the literature. Epilepsia 1987;28(Suppl 3):37–45.
TwymanRE, RogersCJ, MacdonaldRL. Differential regulation of gamma-aminobutyric acid receptor channels by diazepam and phenobarbital. Ann Neurol 1989;25:213–20.
VermeulenJ, AldenkampAP. Cognitive side-effects of chronic antiepileptic drug treatment: a review of 25 years of research. Epilepsy Res 1995;22:65–95.
ViningEP, MellitisED, DorsenMM, et al. Psychologic and behavioral effects of antiepileptic drugs in children: a double-blind comparison between phenobarbital and valproic acid. Pediatrics 1987;80(2):165–74.
WhiteHS. Clinical significance of animal seizure models and mechanism of action studies of potential antiepileptic drugs. Epilepsia 1997;38(Suppl 1):S9–S17.
WongIC. New antiepileptic drugs: study suggests that under a quarter of patients will still be taking the new drugs after six years. BMJ 1997;314:603–4.