title: Topiramate and cognitive impairment: evidence and clinical implications.
abstract: Topiramate is an antiepileptic drug (AED) with multiple mechanisms of action that has been shown to be effective in a number of neuropsychiatric disorders. However, cognitive dysfunction is frequently observed in such patients, often representing a relevant challenge in their management. Moreover, there is a long-held recognition that AEDs may profoundly affect cognitive functions. This paper reviews available data on cognitive adverse events in patients with neurological disorders treated with topiramate, discussing the role of different contributing factors such as the pharmacological properties of the drug, the specific features of the brain disorder, and other variables pertinent to the discussion. All studies agree that up to 10% of patients may complain of treatment-emergent adverse events on cognition. Such problems occur early during treatment (i.e. within 6 weeks) and emerge in a dose-dependent fashion, suggesting that such prevalence may be significantly reduced using the drug in monotherapy and adopting individualized doses and titration schedules. The magnitude of the problem is generally mild to moderate and the subjective perception of the patient needs to be taken into account. In fact, apart from language problems, data are not conclusive. Comparisons with new AEDs are limited to levetiracetam and lamotrigine, in both cases generally disfavoring topiramate, while data regarding first-generation AEDs show clear differences only for verbal fluency.
authors.affiliation: Division of Neurology, University Hospital Maggiore della Carità, C.so Mazzini 18, 28100 Novara, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Mula
keywords: adverse event; antiepileptic drugs; cognition; epilepsy; headache; neuropsychology; topiramate
references.citation: Epilepsia. 2003 May;44(5):659-63
references.pmid: 12752464
references.citation: Clin J Pain. 2006 Jul-Aug;22(6):526-31
references.pmid: 16788338
references.citation: Neurology. 2004 Jan 27;62(2):299-300
references.pmid: 14745074
references.citation: Epilepsy Res. 1997 Oct;28(3):167-79
references.pmid: 9332882
references.citation: Cephalalgia. 2007 Jul;27(7):814-23
references.pmid: 17441971
references.citation: Headache. 2009 Nov-Dec;49(10):1454-65
references.pmid: 19804392
references.citation: Clin Neuropharmacol. 2001 Sep-Oct;24(5):284-9
references.pmid: 11586113
references.citation: Epilepsia. 1985 May-Jun;26(3):212-20
references.pmid: 4006880
references.citation: Neurology. 2003 May 13;60(9):1483-8
references.pmid: 12743236
references.citation: Neurology. 2003 Apr 8;60(7):1104-7
references.pmid: 12682314
references.citation: Neurology. 1996 Jun;46(6):1678-83
references.pmid: 8649569
references.citation: J Clin Psychiatry. 2005;66 Suppl 2:9-13
references.pmid: 15762814
references.citation: J Child Neurol. 2007 Jun;22(6):693-9
references.pmid: 17641254
references.citation: Epilepsia. 2000;41(S1):3-9
references.pmid: 10768292
references.citation: Neurology. 1999 Jun 10;52(9):1882-7
references.pmid: 10371538
references.citation: Epilepsy Behav. 2006 Jun;8(4):736-41
references.pmid: 16647301
references.citation: Epilepsia. 2011 Jun;52(6):1084-91
references.pmid: 21453356
references.citation: Clin Pharmacol Ther. 2009 Mar;85(3):283-8
references.pmid: 18987621
references.citation: Acta Neurol Scand. 2011 Jan;123(1):54-9
references.pmid: 20219018
references.citation: Headache. 2005 Nov-Dec;45(10):1304-12
references.pmid: 16324162
references.citation: Curr Med Res Opin. 2010 May;26(5):1119-29
references.pmid: 20225996
references.citation: Clin Neuropharmacol. 2011 Mar-Apr;34(2):74-8
references.pmid: 21412201
references.citation: Epilepsia. 1975 Nov;16(4):617-25
references.pmid: 9890789
references.citation: Headache. 2005 Sep;45(8):1023-30
references.pmid: 16109116
references.citation: Cephalalgia. 2011 Jan;31(1):18-30
references.pmid: 20974598
references.citation: Pediatr Neurol. 2010 Mar;42(3):187-95
references.pmid: 20159428
references.citation: Epileptic Disord. 2004 Jun;6(2):57-75
references.pmid: 15246950
references.citation: CNS Drugs. 2008;22(9):739-60
references.pmid: 18698874
references.citation: Neurology. 2005 Jun 28;64(12):2108-14
references.pmid: 15985582
references.citation: Acta Neurol Scand. 2008 Sep;118(3):164-74
references.pmid: 18384458
references.citation: Lancet. 2007 Mar 24;369(9566):1000-15
references.pmid: 17382827
references.citation: Neuropediatrics. 2009 Apr;40(2):61-5
references.pmid: 19809933
references.citation: J Clin Psychiatry. 2003;64 Suppl 8:5-8
references.pmid: 12892535
references.citation: J Neurol Neurosurg Psychiatry. 2000 Nov;69(5):636-41
references.pmid: 11032616
references.citation: J Rheumatol. 1994 Apr;21(4):748-9
references.pmid: 7913503
references.citation: Neurology. 1998 Aug;51(2):627-9
references.pmid: 9710056
references.citation: Cochrane Database Syst Rev. 2008 Jul 16;(3):CD001417
references.pmid: 18646072
references.citation: Epilepsia. 2003;44 Suppl 4:21-9
references.pmid: 12823566
references.citation: Epilepsy Behav. 2007 May;10(3):486-94
references.pmid: 17409025
references.citation: Epilepsia. 2007 Sep;48(9):1716-1723
references.pmid: 17561952
references.citation: Pediatrics. 2009 Mar;123(3):924-34
references.pmid: 19255022
references.citation: Neurology. 2010 Mar 2;74(9):714-20
references.pmid: 20089937
references.citation: Neurol Sci. 2008 May;29 Suppl 1:S141-3
references.pmid: 18545916
references.citation: Epilepsy Behav. 2003 Oct;4(5):548-52
references.pmid: 14527497
references.citation: Drugs. 2000 Nov;60(5):1029-52
references.pmid: 11129121
references.citation: Headache. 2007 Nov-Dec;47(10):1398-408
references.pmid: 18052949
references.citation: Epilepsia. 2000;41(S1):21-4
references.pmid: 10768295
references.citation: Seizure. 2006 Sep;15(6):405-8
references.pmid: 16809055
references.citation: Epilepsia. 2000;41(S1):40-4
references.pmid: 10768299
references.citation: Epilepsy Behav. 2007 Feb;10(1):192-4
references.pmid: 17166774
references.citation: Epilepsy Behav. 2006 Aug;9(1):181-5
references.pmid: 16793345
references.citation: Psychiatry Clin Neurosci. 2008 Oct;62(5):548-53
references.pmid: 18950374
references.citation: Epilepsia. 2008 Jul;49(7):1180-5
references.pmid: 18494791
references.citation: Epilepsy Behav. 2007 May;10(3):463-9
references.pmid: 17337249
references.citation: Neurology. 2005 Jun 14;64(11):1868-73
references.pmid: 15955935
references.citation: CNS Drugs. 2008;22(1):27-47
references.pmid: 18072813
references.citation: Neurology. 2000 Jan 11;54(1):271-2
references.pmid: 10636175
references.citation: Headache. 2009 Sep;49(8):1153-62
references.pmid: 19719543
references.citation: Neurology. 2006 Aug 8;67(3):400-6
references.pmid: 16894098
references.citation: Epilepsy Behav. 2009 Mar;14(3):459-64
references.pmid: 19130899
references.citation: Epilepsy Res. 1997 Apr;27(1):29-32
references.pmid: 9169288
references.citation: Neurology. 1999 Jan 15;52(2):321-7
references.pmid: 9932951
references.citation: Neurology. 2011 Jan 11;76(2):131-7
references.pmid: 21148119
references.citation: Neurology. 2002 Feb 12;58(3):368-72
references.pmid: 11839834
references.citation: Pain Med. 2008 Mar;9(2):175-85
references.pmid: 18298700
references.citation: Headache. 2007 Feb;47(2):170-80
references.pmid: 17300356
references.citation: J Headache Pain. 2010 Feb;11(1):33-44
references.pmid: 19894100
references.citation: Neuropediatrics. 2010 Jun;41(3):113-20
references.pmid: 20859829
references.citation: Epilepsy Behav. 2001 Dec;2(6):579-584
references.pmid: 12609393
references.citation: Epilepsia. 1994 Mar-Apr;35(2):450-60
references.pmid: 8156972
references.citation: Epilepsy Behav. 2008 Feb;12(2):253-6
references.pmid: 17962081
references.citation: J Headache Pain. 2008 Jun;9(3):147-50
references.pmid: 18385933
references.citation: Epilepsy Behav. 2006 Feb;8(1):181-91
references.pmid: 16377253
references.citation: J Clin Psychopharmacol. 2007 Jun;27(3):263-72
references.pmid: 17502773
references.citation: Epilepsia. 2000 Sep;41(9):1167-78
references.pmid: 10999556
references.citation: Clin Neurol Neurosurg. 2008 Dec;110(10):979-84
references.pmid: 18620801
references.citation: Clin Neuropharmacol. 2008 Mar-Apr;31(2):97-103
references.pmid: 18382182
references.citation: Neurology. 1999 Apr 22;52(7):1330-7
references.pmid: 10227614
references.citation: Arch Neurol. 2010 Apr;67(4):408-15
references.pmid: 20385905
references.citation: Neurology. 2002 Sep 10;59(5 Suppl 2):S14-7
references.pmid: 12221151
references.citation: Seizure. 2007 Oct;16(7):593-600
references.pmid: 17543544
references.citation: Behav Neurol. 2006;17(1):69-75
references.pmid: 16720961
references.citation: Epilepsia. 2010 Oct;51(10):1970-7
references.pmid: 20633037
references.citation: Neurology. 2000 Jan 11;54(1):270-1; author reply 271-2
references.pmid: 10636174
references.citation: Acta Neurol Scand. 2005 Sep;112(3):144-50
references.pmid: 16097955
references.citation: Neurology. 2006 Mar 14;66(5):672-7
references.pmid: 16436648
references.citation: Epileptic Disord. 2005 Sep;7(3):237-48
references.pmid: 16162434
references.citation: Lancet. 2007 Mar 24;369(9566):1016-26
references.pmid: 17382828
references.citation: Epilepsia. 2000;41(S1):52-60
references.pmid: 10768302
references.citation: J Int Med Res. 2011;39(2):408-15
references.pmid: 21672344
references.citation: Acta Neurol Scand. 2005 Oct;112(4):214-22
references.pmid: 16146489
references.citation: Clin Electroencephalogr. 2003 Apr;34(2):87-92
references.pmid: 12784907
references.citation: CNS Drugs. 2009;23(2):121-37
references.pmid: 19173372
references.citation: Epilepsia. 1996 Jun;37(6):539-43
references.pmid: 8641230
references.citation: Curr Opin Neurol. 2011 Jun;24(3):203-10
references.pmid: 21464715
references.citation: Epilepsia. 2006 Apr;47(4):695-703
references.pmid: 16650135
references.citation: Epilepsy Res. 2003 May;54(2-3):171-8
references.pmid: 12837568
references.citation: Br J Pharmacol. 2004 Jul;142(5):831-42
references.pmid: 15197104
references.citation: Epilepsia. 2000;41(S1):10-6
references.pmid: 10768293
references.citation: Epilepsia. 2009 May;50(5):1072-6
references.pmid: 19178563