Article metrics

  • citations in SCindeks: 0
  • citations in CrossRef:0
  • citations in Google Scholar:[=>]
  • visits in previous 30 days:9
  • full-text downloads in 30 days:1
article: 2 from 9  
Back back to result list
Srpski arhiv za celokupno lekarstvo
2019, vol. 147, iss. 3-4, pp. 193-1998
article language: Serbian
document type: Original Paper
published on: 07/07/2019
doi: 10.2298/SARH171225066M
The effects of topiramate on cognitive functions of patients with focal epilepsy: The follow-up study in a Serbian sample
aUniversity of Priština - Kosovska Mitrovica, Faculty of Medicine + Priština Clinical-hospital Center, Gračanica
bClinical Center of Serbia, Clinic for Neurology, Belgrade
cUniversity of Priština - Kosovska Mitrovica, Faculty of Medicine
dUniversity of Belgrade, Faculty of Medicine



Introduction/Objective the aim of this follow-up study was to determine the effects of topiramate therapy on cognitive functions in patients with pharmacoresistant focal epilepsy. Methods the study sample comprised of 40 topiramate naive patients. The topiramate starting dose was 25 mg, with a fortnightly titration schedule of 25 mg. A wide range of cognitive functions was evaluated through extensive neuropsychological testing at baseline and six months after reaching the target dose (200 mg/day). Results the most common side effects following the introduction of topiramate were cognitive impairments , reported by 45% of the participants. The neuropsychological scores on attention, executive function, verbal content recall, improved cognitive flexibility, as well as visuospatial ability and speech, obtained at six-month follow-up were significantly lower than at baseline. However, statistically significant correlation between neuropsychological scores and the number of antiepileptic drugs taken alongside topiramate could not be established. Similarly, no statistically significant differences were noted between the percentage of reduced neuropsychological scores at follow-up pertaining to patients with lower and higher baseline cognitive performance. Moreover, regression analysis indicates that the percentage change in the majority of cognitive scores is unrelated to the age at the epilepsy onset, epilepsy duration, presence of brain pathology on magnetic resonance imaging and percentage change in the depression scale score. Conclusion Despite slow introduction and administration of a relatively small dose, topiramate exhibits adverse effects on a wide range of cognitive functions, which appear unrelated to the number of additional antiepileptic drugs, baseline cognitive functioning, age at the onset of epilepsy and its duration, presence of brain pathology and the extent of depressive symptoms.



Aldenkamp, A.P., Baker, G. (2001) A Systematic Review of the Effects of Lamotrigine on Cognitive Function and Quality of Life. Epilepsy & Behavior, 2(2): 85-91
Arif, H., Buchsbaum, R., Weintraub, D., Pierro, J., Jr. Stanley, R. R., Hirsch, L.J. (2009) Patient-reported cognitive side effects of antiepileptic drugs: Predictors and comparison of all commonly used antiepileptic drugs. Epilepsy & Behavior, 14(1): 202-209
Baker, G.A., Taylor, J., Aldenkamp, A.P. (2011) Newly diagnosed epilepsy: Cognitive outcome after 12 months. Epilepsia, 52(6): 1084-1091
Burton, L.A., Harden, C. (1997) Effect of topiramate on attention. Epilepsy Research, 27(1): 29-32
Folstein, M.F., Folstein, S.E., McHugh, P.R. (1975) 'Mini-mental state': A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res, 12(3): 189-98
Gerber, P.E., Hamiwka, L., Connolly, M.B., Farrell, K. (2000) Factors associated with behavioral and cognitive abnormalities in children receiving Topiramate. Pediatric Neurology, 22(3): 200-203
Godefroy, O., Azouvi, P., Robert, P., Roussel, M., LeGall, D., Meulemans, T. (2010) Dysexecutive syndrome: Diagnostic criteria and validation study. Annals of Neurology, 68(6): 855-864
Goodglas, H., Kaplan, E. (1983) The assessment of aphasia and related disorders. Philadelphia: Lea&Febiger
Guberman, A., Neto, W., Gassmann-Mayer, C. (2002) Low-dose topiramate in adults with treatment-resistant partial-onset seizures. Acta Neurologica Scandinavica, 106(4): 183-189
Hamilton, M. (2011) Development of a Rating Scale for Primary Depressive Illness. British Journal of Social and Clinical Psychology, 6(4): 278-296
Javed, A., Cohen, B., Detyniecki, K., Hirsch, L.J., Legge, A., Chen, B., Bazil, C., Kato, K., Buchsbaum, R., Choi, H. (2015) Rates and predictors of patient-reported cognitive side effects of antiepileptic drugs: An extended follow-up. Seizure, 29(): 34-40
Jette, N., Hemming, K., Hutton, J.L., Marson, A.G. (2008) Topiramate add-on for drug-resistant partial epilepsy. Cochrane Database of Systematic Reviews, 16(3):CD001417
Kanner, A.M., Wuu, J., Faught, E., Tatum, W.O., Fix, A., French, J.A. (2003) A past psychiatric history may be a risk factor for topiramate-related psychiatric and cognitive adverse events. Epilepsy & Behavior, 4(5): 548-552
Lee, H., Jung, D., Suh, C., Kwon, S., Park, S. (2006) Cognitive effects of low-dose topiramate monotherapy in epilepsy patients: A 1-year follow-up. Epilepsy & Behavior, 8(4): 736-741
Lee, S., Sziklas, V., Andermann, F., Farnham, S., Risse, G., Gustafson, M., Gates, J., Penovich, P., Al-Asmi, A., Dubeau, F., Jones-Gotman, M. (2003) The Effects of Adjunctive Topiramate on Cognitive Function in Patients with Epilepsy. Epilepsia, 44(3): 339-347
Lezak, M.D. (1995) Neuropsychological assessment. Oxford, itd.Oxford: Oxford University Press
Mula, M., Trimble, M.R., Sander, J.W. A. S. (2003) The Role of Hippocampal Sclerosis in Topiramate-related Depression and Cognitive Deficits in People with Epilepsy. Epilepsia, 44(12): 1573-1577
Mula, M. (2012) Topiramate and cognitive impairment: evidence and clinical implications. Therapeutic Advances in Drug Safety, 3(6): 279-289
Mula, M., Trimble, Michael R., Lhatoo, Samden D., Sander, Josemir W. A. S. (2003) Topiramate and Psychiatric Adverse Events in Patients with Epilepsy. Epilepsia, 44(5): 659-663
Osterrieth, P.A. (1944) Filetest de copie d'une figure complex: Contribution a l'etude de la perception et de la memoire. Archives de Psychologie, 30: 286-356
Pavlović, D.M. (2003) Diagnostic tests in neuropsychology. Beograd: Grafos
Petroff, O.A. C., Hyder, F., Rothman, D.L., Mattson, R.H. (2001) Topiramate Rapidly Raises Brain GABA in Epilepsy Patients. Epilepsia, 42(4): 543-548
Privitera, M., Fincham, R., Penry, J., Reife, R., Kramer, L., Pledger, G., Karim, R. (1996) Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 600-, 800-, and 1000-mg daily dosages. Topiramate YE Study Group. Neurology, 46(6): 1678-1683
Pulman, J., Jette, N., Dykeman, J., Hemming, K., Hutton, J.L., Marson, A.G. (2014) Topiramate add-on for drug-resistant partial epilepsy. Cochrane Database of Systematic Reviews, (2):1-52
Ramsay, E., Faught, E., Krumholz, A., Naritoku, D., Privitera, M., Schwarzman, L., Mao, L., Wiegand, F., Hulihan, J. (2010) Efficacy, tolerability, and safety of rapid initiation of topiramate versus phenytoin in patients with new-onset epilepsy: A randomized double-blind clinical trial. Epilepsia, 51(10): 1970-1977
Reife, R. A., Pledger, G. W. (1997) Topiramate as Adjunctive Therapy in Refractory Partial Epilepsy: Pooled Analysis of Data from Five Double-Blind, Placebo-Controlled Trials. Epilepsia, 38(s1): S31-S33
Rey, A. (1941) L'examen psychologique dans les cas d'encéphalopathie traumatique. Archives de Psychologie, 28, 286-340
Roerts, A., Robbins, T., Weiskrantz, L. (2002) The Prefrontal Cortex: Executive and Cognitive Functions. Oxford: Oxford University Press
Sommer, B.R., Mitchell, E.L., Wroolie, T.E. (2013) Topiramate: Effects on cognition in patients with epilepsy, migraine headache and obesity. Therapeutic Advances in Neurological Disorders, 6(4): 211-227
Tatum, W. O., French, J. A., Faught, E., Morris, G. L., Liporace, J., Kanner, A., Goff, S. L., Winters, L., Fix, A. (2002) Postmarketing Experience with Topiramate and Cognition. Epilepsia, 42(9): 1134-1140
Thompson, P.J. (2000) Effects of topiramate on cognitive function. Journal of Neurology, Neurosurgery & Psychiatry, 69(5): 636-641
Wechsler, D. (1987) Wechsler's Memory Scale-Revised (WMS-R), manual. San Antonio, TX: The Psychological Corporation, Harcourt Brace Jovanovich