Antiepileptic drug-induced cognitive adverse effects: Potential mechanisms and contributing factors

CNS Drugs

Volumn 23, Issue 2, 2009, Pages 121-137

  Mula, Marco ^a   Trimble, Michael R ^b  

^a UNIVERSITY OF EASTERN PIEDMONT   (Italy)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTICONVULSIVE AGENT; CARBAMAZEPINE; ETHOSUXIMIDE; ETIRACETAM; GABAPENTIN; LAMOTRIGINE; OXCARBAZEPINE; PHENOBARBITAL; PHENYTOIN; PREGABALIN; TIAGABINE; TOPIRAMATE; VALPROIC ACID; VIGABATRIN; ZONISAMIDE;

CLINICAL TRIAL; COGNITIVE DEFECT; DISEASE ASSOCIATION; DRUG MECHANISM; EPILEPSY; HUMAN; MEMORY DISORDER; MOOD; NEUROPSYCHOLOGICAL TEST; PRIORITY JOURNAL; REVIEW; SEIZURE;

AGING; ANTICONVULSANTS; CLINICAL TRIALS AS TOPIC; COGNITION DISORDERS; DRUG EVALUATION; EPILEPSY; HUMANS; MOOD DISORDERS; POLYPHARMACY; RESEARCH DESIGN; SEIZURES;

EID: 59149102224     PISSN: 11727047     EISSN: None     Source Type: Journal    
DOI: 10.2165/00023210-200923020-00003     Document Type: Review

References (107)

1. Meador KJ. Cognitive and memory effects of the new antiepileptic drugs. Epilepsy Res 2006; 68: 63-7
2. Trimble MR, Dodson WE. Epilepsy and quality of life. New York: Raven Press, 1994
3. Perucca E. Withdrawing antiepileptic drugs in seizure-free patients: what are the cognitive benefits? Nat Clin Pract Neurol 2007; 3: 194-5
4. Thompson PJ, Trimble MR. Further studies on anticonvulsant drugs and seizures. Acta Neurol Scand Suppl 1981; 89: 51-8
5. Thompson PJ, Trimble MR. Sodium valproate and cognitive functioning in normal volunteers. Br J Clin Pharmacol 1981; 12: 819-24
6. Aldenkamp AP. Effects of antiepileptic drugs on cognition. Epilepsia 2001; 42 Suppl. 1: 46-9
7. 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
8. Ortinski P, Meador KJ. Cognitive side effects of antiepileptic drugs. Epilepsy Beha 2004; 5 Suppl. 1: S60-5
9. Aldenkamp AP. Antiepileptic drug treatment and epileptic seizures: effects on cognitive function. In: Trimble MR, Schmitz B, editors. The neuropsychiatry of epilepsy. Cambridge: Cambridge University Press, 2002: 256-65
10. MacLeod CM, Dekabian AS, Hunt E. Memory impairment in epileptic patients: selective effects of phenobarbital concentration. Science 1978; 202: 1102-4
11. Gallassi R, Morreale A, Di Sarro R, et al. Cognitive effects of antiepileptic drug discontinuation. Epilepsia 1992; 33 Suppl. 6: S41-4
12. Vining EP, Mellitis ED, Dorsen MM, et al. Psychologic and behavioral effects of antiepileptic drugs in children: a double-blind comparison between phenobarbital and valproic acid. Pediatrics 1987; 80: 165-74
13. Calandre EP, Dominguez-Granados R, Gomez-Rubio M, et al. Cognitive effects of long-term treatment with phenobarbital and valproic acid in school children. Acta Neurol Scand 1990; 81: 504-6
14. Meador KJ, Loring DW, Huh K, et al. Comparative cognitive effects of anticonvulsants. Neurology 1990; 40: 391-4
15. Smith WL, Lowrey JB. Effects of diphenylhydantoin on mental abilities in the elderly. J Am Geriatr Soc 1975; 23: 207-11
16. Thompson P, Huppert F, Trimble M. Anticonvulsant drugs, cognitive function and memory. Acta Neurol Scand Suppl 1980; 80: 75-81
17. Thompson P, Huppert FA, Trimble M. Phenytoin and cognitive function: effects on normal volunteers and implications for epilepsy. Br J Clin Psychol 1981; 20: 155-62
18. Meador KJ, Loring DW, Allen ME, et al. Comparative cognitive effects of carbamazepine and phenytoin in healthy adults. Neurology 1991; 41: 1537-40
19. Meador KJ, Loring DW, Abney OL, et al. Effects of carbamazepine and phenytoin on EEG and memory in healthy adults. Epilepsia 1993; 34: 153-7
20. 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
21. Thompson PJ, Trimble MR. Anticonvulsant drugs and cognitive functions. Epilepsia 1982; 23: 531-44
22. Craig I, Tallis R. Impact of valproate and phenytoin on cognitive function in elderly patients: results of a singleblind randomized comparative study. Epilepsia 1994; 35: 381-90
23. 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
24. Meador KJ, Loring DW, Hulihan JF, et al. Differential cognitive and behavioral effects of topiramate and valproate. Neurology 2003; 60: 1483-8
25. Remy C, Beaumont D. Efficacy and safety of vigabatrin in the long-term treatment of refractory epilepsy. Br J Clin Pharmacol 1989; 27 Suppl. 1: 125-9S
26. Tartara A, Manni R, Galimberti CA, et al. Vigabatrin in the treatment of epilepsy: a long-term follow-up study. J Neurol Neurosurg Psychiatry 1989; 52: 467-71
27. Ylinen A, Kalviainen R, Riekkinen Sr SJ. Long-term efficacy and cognitive effects of vigabatrin. Acta Neurol Scand Suppl 1995; 162: 47-50
28. McGuire AM, Duncan JS, Trimble MR. Effects of vigabatrin on cognitive function and mood when used as add-on therapy in patients with intractable epilepsy. Epilepsia 1992; 33: 128-34
29. Gillham RA, Blacklaw J, McKee PJ, et al. Effect of vigabatrin on sedation and cognitive function in patients with refractory epilepsy. J Neurol Neurosurg Psychiatry 1993; 56: 1271-5
30. Dodrill CB, Arnett JL, Sommerville KW, et al. Evaluation of the effects of vigabatrin on cognitive abilities and quality of life in epilepsy. Neurology 1993; 43: 2501-7
31. Provinciali L, Bartolini M, Mari F, et al. Influence of vigabatrin on cognitive performances and behaviour in patients with drug-resistant epilepsy. Acta Neurol Scand 1996; 94: 12-8
32. Monaco F, Torta R, Cicolin A, et al. Lack of association between vigabatrin and impaired cognition. J Int Med Res 1997; 25: 296-301
33. Dodrill CB, Arnett JL, Sommerville KW, et al. Effects of differing dosages of vigabatrin (Sabril) on cognitive abilities and quality of life in epilepsy. Epilepsia 1995; 36: 164-73
34. 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
35. 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
36. 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
37. Banks GK, Beran RG. Neuropsychological assessment in lamotrigine treated epileptic patients. Clin Exp Neurol 1991; 28: 230-7
38. Placidi F, Marciani MG, Diomedi M, et al. Effects of lamotrigine on nocturnal sleep, daytime somnolence and cognitive functions in focal epilepsy. Acta Neurol Scand 2000; 102: 81-6
39. Blum D, Meador K, Biton V, et al. Cognitive effects of lamotrigine compared with topiramate in patients with epilepsy. Neurology 2006; 67: 400-6
40. Leach JP, 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: 372-6
41. Dodrill CB, Arnett JL, Hayes AG, et al. Cognitive abilities and adjustment with gabapentin: results of a multisite study. Epilepsy Res 1999; 35: 109-21
42. Sveinbjornsdottir S, Sander JW, Patsalos PN, et al. Neuropsychological effects of tiagabine, a potential new antiepileptic drug. Seizure 1994; 3: 29-35
43. Kalviainen R, Aikia M, Mervaala E, et al. Long-term cognitive and EEG effects of tiagabine in drug-resistant partial epilepsy. Epilepsy Res 1996; 25: 291-7
44. Dodrill CB, Arnett JL, Sommerville KW, et al. Cognitive and quality of life effects of differing dosages of tiagabine in epilepsy. Neurology 1997; 48: 1025-31
45. Dodrill CB, Arnett JL, Shu V, et al. Effects of tiagabine monotherapy on abilities, adjustment, and mood. Epilepsia 1998; 39: 33-42
46. Dodrill CB, Arnett JL, Deaton R, et al. Tiagabine versus phenytoin and carbamazepine as add-on therapies: effects on abilities, adjustment, andmood. Epilepsy Res 2000; 42: 123-32
47. 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: 373-81
48. Burton LA, Harden C. Effect of topiramate on attention. Epilepsy Res 1997; 27: 29-32
49. Thompson PJ, Baxendale SA, Duncan JS, et al. Effects of topiramate on cognitive function. J Neurol Neurosurg Psychiatry 2000; 69: 636-41
50. Lee HW, Jung DK, Suh CK, et al. Cognitive effects of low-dose topiramate monotherapy in epilepsy patients: a 1-year follow-up. Epilepsy Behav 2006; 8: 736-41
51. Aldenkamp AP, Baker G, Mulder OG, 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 partialonset seizures. Epilepsia 2000; 41: 1167-78
52. Neyens LG, Alpherts WC, Aldenkamp AP. Cognitive effects of a new pyrrolidine derivative (levetiracetam) in patients with epilepsy. Prog Neuropsychopharmacol Biol Psychiatry 1995; 19: 411-9
53. 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: 486-94
54. Berent S, Sackellares JC, Giordani B, et al. Zonisamide (CI-912) and cognition: results from preliminary study. Epilepsia 1987; 28: 61-7
55. Park SP, Hwang YH, Lee HW, et al. Long-term cognitive and mood effects of zonisamide monotherapy in epilepsy patients. Epilepsy Behav 2008; 12: 102-8
56. Ciesielski AS, Samson S, Steinhoff BJ. Neuropsychological and psychiatric impact of add-on titration of pregabalin versus levetiracetam: a comparative short-term study. Epilepsy Behav 2006; 9: 424-31
57. Aldenkamp AP, Dreifuss FE, Reiner WO. Epilepsy in children and adolescents. New York: CRC Publishers, 1995
58. Stewart SA. The effects of benzodiazepines on cognition. J Clin Psychiatry 2005; 66 Suppl. 2: 9-13
59. Bialer M, Johannessen SI, Kupferberg HJ, et al. Progress report on new antiepileptic drugs: a summary of the Eighth Eilat Conference (EILAT VIII). Epilepsy Res 2007; 73: 1-52
60. Rogawski MA, Löscher W. The neurobiology of antiepileptic drugs. Nat Rev Neurosci 2004; 5: 553-64
61. Salinsky MC, Storzbach D, Spencer DC, et al. Effects of topiramate and gabapentin on cognitive abilities in healthy volunteers. Neurology 2005; 64: 792-8
62. Meador KJ, Loring DW, Vahle VJ, et al. Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers. Neurology 2005; 64: 2108-14
63. Trimble MR. Anticonvulsant drugs and cognitive function: a review of the literature. Epilepsia 1987; 28 Suppl. 3: S37-45
64. Reynolds EH. Neurological aspects of folate and vitamin B12 metabolism. Clin Haematol 1976; 5: 661-96
65. Reynolds EH, Carney MW, Toone BK. Methylation and mood. Lancet 1984; 2: 196-8
66. Dodrill CB. Correlates of generalized tonic-clonic seizures with intellectual, neuropsychological, emotional, and social function in patients with epilepsy. Epilepsia 1986; 27: 399-411
67. Aldenkamp AP, Bodde N. Behaviour cognition and epilepsy. Acta Neurol Scand Suppl 2005; 182: 19-25
68. Pincus JH, Tucker GJ. Behavioral neurology. 4th ed. Oxford: Oxford University Press, 2003: 24-5
69. 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
70. Binnie CD. Cognitive impairment during epileptiform discharges: is it ever justifiable to treat the EEG? Lancet Neurol 2003; 2: 725-30
71. Jokeit H, Ebner A. The risk of cognitive decline in patients with refractory temporal lobe epilepsy. In: Trimble MR, Schmitz B, editors. The neuropsychiatry of epilepsy. Cambridge: Cambridge University Press, 2002: 152-63
72. Gordon N. The Landau-Kleffner syndrome: increased understanding. Brain Dev 1997; 19: 311-6
73. Baxendale SA, van Paesschen W, Thompson PJ, et al. The relationship between quantitative MRI and neuropsychological functioning in temporal lobe epilepsy. Epilepsia 1998; 39: 158-66
74. Helmstaedter C. Behavioral aspects of frontal lobe epilepsy. Epilepsy Behav 2001; 2: 384-95
75. Mula M, Trimble MR, Thompson P, et al. Topiramate and word-finding difficulties in patients with epilepsy. Neurology 2003; 60: 1104-7
76. Kanner AM, Wuu J, Faught E, et al. A past psychiatric history may be a risk factor for topiramate-related psychiatric and cognitive adverse events. Epilepsy Behav 2003; 4: 548-52
77. Mula M, Trimble MR, Sander JW. The role of hippocampal sclerosis in topiramate-related depression and cognitive deficits in people with epilepsy. Epilepsia 2003; 44: 1573-7
78. Herrmann DJ. Know the memory: the use of questionnaires to assess and study memory. Psychol Bull 1982; 92: 434-52
79. 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
80. Aldenkamp AP, Baker G, Pieters MS, et al. The neurotoxicity scale: the validity of a patient-based scale, assessing neurotoxicity. Epilepsy Res 1995; 20: 229-39
81. 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
82. Dodrill CB, Troupin AS. Neuropsychological effects of carbamazepine and phenytoin: a reanalysis. Neurology 1991; 41: 141-3
83. Herranz JL, Arteaga R, Armijo JA. Side effects of sodium valproate in monotherapy controlled by plasma levels: a study in 88 pediatric patients. Epilepsia 1982; 23: 203-14
84. Aldenkamp AP, Alpherts WC, Moerland MC, et al. Controlled release carbamazepine: cognitive side effects in patients with epilepsy. Epilepsia 1987; 28: 507-14
85. Pieters MS, Jennekens-Schinkel A, Stijnen T, et al. Carbamazepine (CBZ) controlled release compared with conventional CBZ: a controlled study of attention and vigilance in children with epilepsy. Epilepsia 1992 Nov-Dec; 33 (6): 1137-44
86. Brouwer OF, Pieters MS, Edelbroek PM, et al. Conventional and controlled release valproate in children with epilepsy: a cross-over study comparing plasma levels and cognitive performances. Epilepsy Res 1992; 13: 245-53
87. Bialer M. Extended-release formulations for the treatment of epilepsy. CNS Drugs 2007; 21 (9): 765-74
88. Bialer M. Generic products of antiepileptic drugs (AEDs): is it an issue? Epilepsia 2007 Oct; 48 (10): 1825-32
89. Aldenkamp AP, Rentmeester T, Hulsman J, et al. Pharmacokinetics and cognitive effects of carbamazepine formulations with different dissolution rates. Eur J Clin Pharmacol 1998; 54: 185-92
90. Perucca E. Clinical pharmacokinetics of new-generation antiepileptic drugs at the extremes of age. Clin Pharmacokinet 2006; 45: 351-63
91. Motamedi G, Meador K. Epilepsy and cognition. Epilepsy Behav 2003; 4 Suppl. 2: S25-38
92. Bergin AM. Pharmacotherapy of paediatric epilepsy. Expert Opin Pharmacother 2003; 4: 421-31
93. Loring DW, Meador KJ. Cognitive side effects of antiepileptic drugs in children. Neurology 2004; 62: 872-7
94. Vinten J, Adab N, Kini U, et al. Neuropsychological effects of exposure to anticonvulsant medication in utero. Neurology 2005; 64: 949-54
95. Meador KJ, Baker G, Cohen MJ, et al. Cognitive/behavioral teratogenetic effects of antiepileptic drugs. Epilepsy Behav 2007; 11: 292-302
96. Gray SL, Lai KV, Larson EB. Drug-induced cognition disorders in the elderly: incidence, prevention and management. Drug Saf 1999; 21: 101-22
97. Drane DL, Meador KJ. Epilepsy anticonvulsant drugs and cognition. Baillieres Clin Neurol 1996; 5: 877-85
98. Butler CR, Graham KS, Hodges JR, et al. The syndrome of transient epileptic amnesia. Ann Neurol 2007; 61: 587-98
99. Vermeulen J, Aldenkamp AP. Cognitive side-effects of chronic antiepileptic drug treatment: a review of 25 years of research. Epilepsy Res 1995; 22: 65-95
100. Cochrane HC, Marson AG, Baker GA, et al. Neuropsychological outcomes in randomized controlled trials of antiepileptic drugs: a systematic review of methodology and reporting standards. Epilepsia 1998; 39: 1088-97
101. Dodrill CB. A neuropsychological battery for epilepsy. Epilepsia 1978; 19: 611-23
102. Alpherts WC, Aldenkamp AP. Computerized neuropsychological assessment of cognitive functioning in children with epilepsy. Epilepsia 1990; 31 Suppl. 4: S35-40
103. 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
104. McCaffrey RJ, Westervelt HJ. Issues associated with repeated neuropsychological assessments. Neuropsychol Rev 1995; 5: 203-21
105. Seidenberg M, O'Leary DS, Giordani B, et al. Test-retest IQ changes of epilepsy patients: assessing the influence of practice effects. J Clin Neuropsychol 1981; 3: 237-55
106. Austin JK, Huberty TJ, Huster GA, et al. Does academic achievement in children with epilepsy change over time? Dev Med Child Neurol 1999; 41: 473-9
107. Dreifuss FE. Cognitive function: victim of disease or hostage to treatment? Epilepsia 1992; 33 Suppl. 1: S7-12