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DOI: 10.1055/s-0028-1090129
© Georg Thieme Verlag KG Stuttgart · New York
Neurokognitive Effekte häufig in der Epilepsiebehandlung eingesetzter Antiepileptika
Neurocognitive Effects of Antiepileptic Drugs Frequently Used in Long-Term Treatment of Epilepsies: A ReviewPublication History
Publication Date:
16 January 2009 (online)
Zusammenfassung
Antiepileptika (AED) verändern, basierend auf sehr unterschiedlichen Mechanismen, die Erregbarkeit von Nervenzellen und können so auch neurokognitive Prozesse beeinflussen. In den vergangenen Jahren wurden mehrere neue Antiepileptika zugelassen, die neben der Epilepsie auch zur Behandlung des neuropathischen Schmerzes und zur Stimmungsstabilisierung in der Psychiatrie eingesetzt werden. Es gibt jedoch nur wenige methodisch hinreichend kontrollierte Studien, die die neurokognitiven Wirkungen von Antiepileptika untersucht haben. Weiterhin fehlen Untersuchungen zu kognitiven Wirkungen neuer Antiepileptika in Kombinationstherapie mit älteren und anderen neuen Antiepileptika. Die Mehrzahl der neueren AED (Gabapentin, Lamotrigin, Levetiracetam, Oxcarbazepin) weisen gegenüber den älteren ein günstigeres neurokognitives Profil auf. Unter den neueren AED besteht bei Topiramat das höchste Risiko für kognitive Störwirkungen, die aber reversibel sind. Die Datenlage für Zonisamid ist für eine abschließende Beurteilung noch unzureichend, aber es verdichten sich Hinweise darauf, dass es häufiger kognitive Störwirkungen induziert als Gabapentin, Levetiracetam und Lamotrigin.
Abstracts
Antiepileptic drugs (AED) alter neuronal excitation levels and may lead to neurocognitive changes. In recent years, several new AEDs have been introduced which are additionally used to treat mood disorders, neuropathic pain and migraine. Generally, very few controlled trials have systematically examined the cognitive side effects of AEDs. In particular, polytherapy with the newer AEDs is under-investigated. In this paper we review the most relevant data pertaining to neurocognitive side effects of AEDs that are currently prescribed in Switzerland for the long-term treatment of epilepsies.
Schlüsselwörter
Antiepileptika - Nebenwirkungen - Kognition - Neuropsychologie - Epilepsie
Key words
antiepileptic drugs - side effects - cognition - neuropsychology - epilepsy
Literatur
- 1 Marques C M, Caboclo L O, da Silva T I. et al . Cognitive decline in temporal lobe epilepsy due to unilateral hippocampal sclerosis. Epilepsy Behav. 2007; 10 477-485
- 2 Jokeit H, Schacher M. Neuropsychological aspects of type of epilepsy and etiological factors in adults. Epilepsy Behav. 2004; 5 (Suppl. 1) S14-20
- 3 Landmark C J. Targets for antiepileptic drugs in the synapse. Med Sci Monit. 2007; 13 RA1-7
- 4 Hessen E, Lossius M I, Reinvang I. et al . Influence of major antiepileptic drugs on attention, reaction time, and speed of information processing: results from a randomized, double-blind, placebo-controlled withdrawal study of seizure-free epilepsy patients receiving monotherapy. Epilepsia. 2006; 47 2038-2045
- 5 Gallassi R, Morreale A, Di Sarro R. et al . Cognitive effects of antiepileptic drug discontinuation. Epilepsia. 1992; 33 (Suppl. 6) S41-44
- 6 Chen Y, Chi Chow J, Lee I. Comparison the cognitive effect of anti-epileptic drugs in seizure-free children with epilepsy before and after drug withdrawal. Epilepsy Res. 2001; 44 65-70
- 7 Martin R, Meador K, Turrentine L. et al . Comparative cognitive effects of carbamazepine and gabapentin in healthy senior adults. Epilepsia. 2001; 42 764-771
- 8 Meador K J, Loring D W, Ray P G. et al . Differential cognitive effects of carbamazepine and gabapentin. Epilepsia. 1999; 40 1279-1285
- 9 Meador K J, Loring D W, Ray P G. et al . Differential cognitive and behavioral effects of carbamazepine and lamotrigine. Neurology. 2001; 56 1177-1182
- 10 Gillham R A, Williams N, Wiedmann K D. et al . Cognitive function in adult epileptic patients established on anticonvulsant monotherapy. Epilepsy Res. 1990; 7 219-225
- 11 Kang H C, Eun B L, Wu Lee C. et al . The effects on cognitive function and behavioral problems of topiramate compared to carbamazepine as monotherapy for children with benign rolandic epilepsy. Epilepsia. 2007; 48 1716-1723
- 12 Aikia M, Jutila L, Salmenpera T. et al . Comparison of the cognitive effects of tiagabine and carbamazepine as monotherapy in newly diagnosed adult patients with partial epilepsy: pooled analysis of two long-term, randomized, follow-up studies. Epilepsia. 2006; 47 1121-1127
- 13 Dodrill C B, Arnett J L, Deaton R. et al . Tiagabine versus phenytoin and carbamazepine as add-on therapies: effects on abilities, adjustment, and mood. Epilepsy Res. 2000; 42 123-132
- 14 Read C L, Stephen L J, Stolarek I H. et al . Cognitive effects of anticonvulsant monotherapy in elderly patients: a placebo-controlled study. Seizure. 1998; 7 159-162
- 15 Kelly K M. Gabapentin. Antiepileptic mechanism of action. Neuropsychobiology. 1998; 38 139-144
- 16 Dodrill C B, Arnett J L, Hayes A G. et al . Cognitive abilities and adjustment with gabapentin: results of a multisite study. Epilepsy Res. 1999; 35 109-121
- 17 Salinsky M C, Binder L M, Oken B S. et al . Effects of gabapentin and carbamazepine on the EEG and cognition in healthy volunteers. Epilepsia. 2002; 43 482-490
- 18 Salinsky M C, Storzbach D, Spencer D C. et al . Effects of topiramate and gabapentin on cognitive abilities in healthy volunteers. Neurology. 2005; 64 792-798
- 19 Mortimore C, Trimble M, Emmers E. Effects of gabapentin on cognition and quality of life in patients with epilepsy. Seizure. 1998; 7 359-364
- 20 Leach J P, Girvan J, Paul A. et al . Gabapentin and cognition: a double blind, dose ranging, placebo controlled study in refractory epilepsy. J Neurol Neurosurg Psychiatry. 1997; 62 372-376
- 21 Hurley S C. Lamotrigine update and its use in mood disorders. Ann Pharmacother. 2002; 36 860-873
- 22 Smith D, Baker G, Davies G. et al . Outcomes of add-on treatment with lamotrigine in partial epilepsy. Epilepsia. 1993; 34 312-322
- 23 Pressler R M, Binnie C D, Coleshill S G. et al . Effect of lamotrigine on cognition in children with epilepsy. Neurology. 2006; 66 1495-1499
- 24 Zoccali R, Muscatello M R, Bruno A. et al . The effect of lamotrigine augmentation of clozapine in a sample of treatment-resistant schizophrenic patients: a double-blind, placebo-controlled study. Schizophr Res. 2007; 93 109-116
- 25 Placidi F, Marciani M G, Diomedi M. et al . Effects of lamotrigine on nocturnal sleep, daytime somnolence and cognitive functions in focal epilepsy. Acta Neurol Scand. 2000; 102 81-86
- 26 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
- 27 Meador K J, Loring D W, Vahle V J. et al . Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers. Neurology. 2005; 64 2108-2114
- 28 Werz M A, Schoenberg M R, Meador K J. et al . Subjective preference for lamotrigine or topiramate in healthy volunteers: relationship to cognitive and behavioral functioning. Epilepsy Behav. 2006; 8 181-191
- 29 Smith M E, Gevins A, McEvoy L K. et al . Distinct cognitive neurophysiologic profiles for lamotrigine and topiramate. Epilepsia. 2006; 47 695-703
- 30 Blum D, Meador K, Biton V. et al . Cognitive effects of lamotrigine compared with topiramate in patients with epilepsy. Neurology. 2006; 67 400-406
- 31 Zhou B, Zhang Q, Tian L. et al . Effects of levetiracetam as an add-on therapy on cognitive function and quality of life in patients with refractory partial seizures. Epilepsy Behav. 2008; 12 305-310
- 32 Ciesielski A S, Samson S, Steinhoff B J. Neuropsychological and psychiatric impact of add-on titration of pregabalin versus levetiracetam: a comparative short-term study. Epilepsy Behav. 2006; 9 424-431
- 33 Gomer B, Wagner K, Frings L. et al . The influence of antiepileptic drugs on cognition: a comparison of levetiracetam with topiramate. Epilepsy Behav. 2007; 10 486-494
- 34 Neyens L G, Alpherts W C, Aldenkamp A P. Cognitive effects of a new pyrrolidine derivative (levetiracetam) in patients with epilepsy. Prog Neuropsychopharmacol Biol Psychiatry. 1995; 19 411-419
- 35 Meador K J, Gevins A, Loring D W. et al . Neuropsychological and neurophysiologic effects of carbamazepine and levetiracetam. Neurology. 2007; 69 2076-2084
- 36 Mecarelli O, Vicenzini E, Pulitano P. et al . Clinical, cognitive, and neurophysiologic correlates of short-term treatment with carbamazepine, oxcarbazepine, and levetiracetam in healthy volunteers. Ann Pharmacother. 2004; 38 1816-1822
- 37 Vajda F J. New antiepileptic drugs. J Clin Neurosci. 2000; 7 88-101
- 38 Tzitiridou M, Panou T, Ramantani G. et al . Oxcarbazepine monotherapy in benign childhood epilepsy with centrotemporal spikes: a clinical and cognitive evaluation. Epilepsy Behav. 2005; 7 458-467
- 39 Donati F, Gobbi G, Campistol J. et al . The cognitive effects of oxcarbazepine versus carbamazepine or valproate in newly diagnosed children with partial seizures. Seizure. 2007; 16 670-679
- 40 Salinsky M C, Spencer D C, Oken B S. et al . Effects of oxcarbazepine and phenytoin on the EEG and cognition in healthy volunteers. Epilepsy Behav. 2004; 5 894-902
- 41 Aikia M, Kalviainen 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
- 42 Twyman R E, Rogers C J, Macdonald R L. Differential regulation of gamma-aminobutyric acid receptor channels by diazepam and phenobarbital. Ann Neurol. 1989; 25 213-220
- 43 Riva D, Devoti M. Discontinuation of phenobarbital in children: effects on neurocognitive behavior. Pediatr Neurol. 1996; 14 36-40
- 44 Tonekaboni S H, Beyraghi N, Tahbaz H S. et al . Neurocognitive effects of phenobarbital discontinuation in epileptic children. Epilepsy Behav. 2006; 8 145-148
- 45 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 1494-1499
- 46 Chen Y J, Kang W M, So W C. Comparison of antiepileptic drugs on cognitive function in newly diagnosed epileptic children: a psychometric and neurophysiological study. Epilepsia. 1996; 37 81-86
- 47 Jokeit H, Kramer G, Ebner A. Do antiepileptic drugs accelerate forgetting?. Epilepsy Behav. 2005; 6 430-432
- 48 Yaari Y, Selzer M E, Pincus J H. Phenytoin: mechanisms of its anticonvulsant action. Ann Neurol. 1986; 20 171-184
- 49 Gallassi R, Morreale A, Lorusso S. et al . Cognitive effects of phenytoin during monotherapy and after withdrawal. Acta Neurol Scand. 1987; 75 258-261
- 50 Gallassi R, Morreale A, Lorusso S. et al . Carbamazepine and phenytoin. Comparison of cognitive effects in epileptic patients during monotherapy and withdrawal. Arch Neurol. 1988; 45 892-894
- 51 Pulliainen V, Jokelainen M. Comparing the cognitive effects of phenytoin and carbamazepine in long-term monotherapy: a two-year follow-up. Epilepsia. 1995; 36 1195-1202
- 52 Duncan J S, Shorvon S D, Trimble M R. Effects of removal of phenytoin, carbamazepine, and valproate on cognitive function. Epilepsia. 1990; 31 584-591
- 53 Brown E S, Stuard G, Liggin J D. et al . Effect of phenytoin on mood and declarative memory during prescription corticosteroid therapy. Biol Psychiatry. 2005; 57 543-548
- 54 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; 35 381-390
- 55 Beenen L F, Lindeboom J, Kasteleijn-Nolst Trenite D G. et al . Comparative double blind clinical trial of phenytoin and sodium valproate as anticonvulsant prophylaxis after craniotomy: efficacy, tolerability, and cognitive effects. J Neurol Neurosurg Psychiatry. 1999; 67 474-480
- 56 Aldenkamp A P, Alpherts W C, Diepman L. et al . Cognitive side-effects of phenytoin compared with carbamazepine in patients with localization-related epilepsy. Epilepsy Res. 1994; 19 37-43
- 57 Aldenkamp A P, Alpherts W C, Blennow G. et al . Withdrawal of antiepileptic medication in children – effects on cognitive function: The Multicenter Holmfrid Study. Neurology. 1993; 43 41-50
- 58 Pulliainen V, Jokelainen M. Effects of phenytoin and carbamazepine on cognitive functions in newly diagnosed epileptic patients. Acta Neurol Scand. 1994; 89 81-86
- 59 Dodrill C B, Troupin A S. Neuropsychological effects of carbamazepine and phenytoin: a reanalysis. Neurology. 1991; 41 141-143
- 60 Dodrill C B, Temkin N R. Motor speed is a contaminating factor in evaluating the „cognitive” effects of phenytoin. Epilepsia. 1989; 30 453-457
- 61 Taylor C P, Angelotti T, Fauman E. Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Res. 2007; 73 137-150
- 62 Hindmarch I, Trick L, Ridout F. A double-blind, placebo- and positive-internal-controlled (alprazolam) investigation of the cognitive and psychomotor profile of pregabalin in healthy volunteers. Psychopharmacology (Berl). 2005; 183 133-143
- 63 Macdonald R L, Kelly K M. Antiepileptic drug mechanisms of action. Epilepsia. 1995; 36 (Suppl. 2) S2-12
- 64 White H S. Molecular pharmacology of topiramate: managing seizures and preventing migraine. Headache. 2005; 45 (Suppl. 1) S48-56
- 65 Fritz N, Glogau S, Hoffmann J. et al . Efficacy and cognitive side effects of tiagabine and topiramate in patients with epilepsy. Epilepsy Behav. 2005; 6 373-381
- 66 Lee H W, Jung D K, Suh C K. et al . Cognitive effects of low-dose topiramate monotherapy in epilepsy patients: A 1-year follow-up. Epilepsy Behav. 2006; 8 736-741
- 67 Romigi A, Cervellino A, Marciani M G. et al . Cognitive and psychiatric effects of topiramate monotherapy in migraine treatment: an open study. Eur J Neurol. 2008; 15 190-195
- 68 Aldenkamp A P, Baker G, Mulder O G. et al . A multicenter, 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 1167-1178
- 69 de Araujo Filho G M, Pascalicchio T F, Lin K. et al . Neuropsychiatric profiles of patients with juvenile myoclonic epilepsy treated with valproate or topiramate. Epilepsy Behav. 2006; 8 606-609
- 70 Kockelmann E, Elger C E, Helmstaedter C. Significant improvement in frontal lobe associated neuropsychological functions after withdrawal of topiramate in epilepsy patients. Epilepsy Res. 2003; 54 171-178
- 71 Kockelmann E, Elger C E, Helmstaedter 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; 5 716-721
- 72 Martin R, Kuzniecky R, Ho S. et al . Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults. Neurology. 1999; 52 321-327
- 73 Meador K J, Loring D W, Hulihan J F. et al . Differential cognitive and behavioral effects of topiramate and valproate. Neurology. 2003; 60 1483-1488
- 74 Rosenberg G. The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees?. Cell Mol Life Sci. 2007; 64 2090-2103
- 75 Thompson P J, Trimble M R. Sodium valproate and cognitive functioning in normal volunteers. Br J Clin Pharmacol. 1981; 12 819-824
- 76 Gallassi R, Morreale A, Lorusso S. et al . Cognitive effects of valproate. Epilepsy Res. 1990; 5 160-164
- 77 Dikmen S S, Machamer J E, Winn H R. et al . Neuropsychological effects of valproate in traumatic brain injury: a randomized trial. Neurology. 2000; 54 895-902
- 78 Senturk V, Goker C, Bilgic A. et al . Impaired verbal memory and otherwise spared cognition in remitted bipolar patients on monotherapy with lithium or valproate. Bipolar Disord. 2007; 9 (Suppl. 1) 136-144
- 79 Helmstaedter C, Wagner G, Elger C E. Differential effects of first antiepileptic drug application on cognition in lesional and non-lesional patients with epilepsy. Seizure. 1993; 2 125-130
- 80 Siren A, Kylliainen A, Tenhunen M. et al . Beneficial effects of antiepileptic medication on absence seizures and cognitive functioning in children. Epilepsy Behav. 2007; 11 85-91
- 81 Wilensky A J, Friel P N, Ojemann L M. et al . Zonisamide in epilepsy: a pilot study. Epilepsia. 1985; 26 212-220
- 82 Berent S, Sackellares J C, Giordani B. et al . Zonisamide (CI-912) and cognition: results from preliminary study. Epilepsia. 1987; 28 61-67
- 83 Ojemann L M, Ojemann G A, Dodrill C B. et al . Language Disturbances as Side Effects of Topiramate and Zonisamide Therapy. Epilepsy Behav. 2001; 2 579-584
- 84 Park S P, Hwang Y H, Lee H W. et al . Long-term cognitive and mood effects of zonisamide monotherapy in epilepsy patients. Epilepsy Behav. 2008; 12 102-108
- 85 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 S53-67
- 86 Cochrane H C, Marson A G, Baker G A. et al . Neuropsychological outcomes in randomized controlled trials of antiepileptic drugs: a systematic review of methodology and reporting standards. Epilepsia. 1998; 39 1088-1097
PD Dr. Hennric Jokeit
Schweizerisches Epilepsie-Zentrum
Bleulerstr. 60
8008 Zürich, Schweiz
Email: h.jokeit@swissepi.ch