Hostname: page-component-586b7cd67f-2brh9 Total loading time: 0 Render date: 2024-11-27T23:04:42.775Z Has data issue: false hasContentIssue false

Improvement in Speeded Cognitive Processing After Anti-epileptic Drug Withdrawal – A Controlled Study in Mono-therapy Patients

Published online by Cambridge University Press:  12 December 2007

Erik Hessen
Affiliation:
Helse Øst Health Services and Department of Neurology, Akershus University Hospital, Norway; Email: [email protected]
Morten I. Lossius
Affiliation:
Helse Øst Health Services and Department of Neurology, Akershus University Hospital, Norway National Center for Epilepsy, Rikshospitalet, University of Oslo, Norway; Email: [email protected]
Ivar Reinvang
Affiliation:
Department of Psychology, University of Oslo, Norway; Email: [email protected]
Leif Gjerstad
Affiliation:
Department of Neurology, Rikshospitalet, University of Oslo, Norway; Email: [email protected]

Extract

ABSTRACT

Background: Anti-epileptic drugs (AEDs) are associated with cognitive side effects. Doubt exists regarding the degree of cognitive effects primarily related to problems with design and methodology in many studies. The aim of the reported study was to assess the effect of AED withdrawal in patients on monotherapy using computerised measures of attention, reaction time and speed of information processing. Methods: One hundred and fifty patients seizure free >2 years on drug monotherapy went through a randomised, double blind, placebo controlled study. All patients were included for 12 months or until seizure relapse. Cognitive function was assessed with the California Computerized Assessment Package at baseline and 7 months after withdrawal. Results: The major finding was that discontinuation of major AEDs significantly improved performance on tests that require complex cognitive processing under time pressure. The difference in speed of cognitive processing between the withdrawal and non-withdrawal groups was between 24 and 43 ms. No significant difference emerged between the groups on simple tasks of attention and reaction time. Most of the patients in the study were treated with carbamazepine and valproate. The outcome of carbamazepine withdrawal was similar to the outcome for the total study population while discontinuation of valproate only revealed a non-significant tendency in the same direction. Interpretation: The results suggest that seizure-free epilepsy patients on monotherapy can obtain improvement in speeded cognitive processing if they withdraw anti-epileptic treatment.

Type
Research Article
Copyright
© 2008 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aldenkamp, A.P. (2001). Effects of antiepileptic drugs on cognition. Epilepsia, 42, 4649.Google Scholar
Aldenkamp, A.P., Alpherts, W.C.J., Blennow, G., et al. (1993). Withdrawal of antiepileptic medication: effects on cognitive function in children: the results of the multicentre “Holmfrid” study. Neurology, 43, 4151.Google Scholar
Baker, G.A., & Marson, A.G. (2001). Cognitive and behavioural assessments in clinical trials: what type of measure? Epilepsy Research, 45, 163167.Google Scholar
Brunbech, L., & Sabers, A. (2002). Effect of antiepileptic drugs on cognitive function in individuals with epilepsy. Drugs, 62, 593604.Google Scholar
Craig, I., & Tallis, R. (1994). Impact of valproat and phenytoin on cognitive function in elderly patients. Results of a single blind randomised comparative study. Epilepsia, 35, 381390.Google Scholar
Galassi, R., Morreale, A., Di Sarro, R., et al. (1992). Cognitive effects of antiepileptic drug discontinuation. Epilepsia, 33, 4144.Google Scholar
Kwan, P., & Brodie, M.J. (2000). Early identification of refractory epilepsy. New England Journal of Medicine, 342, 314319.Google Scholar
Lossius, M.I., Stavem, K., & Gjerstad, L. (1999). Predictors for recurrence of epileptic seizures in a general epilepsy population. Seizure, 8, 476479.Google Scholar
Martin, E.M., Pitrak, D.L., Novak, R.M., Pursell, K.J., & Mullane, K.M. (1999). Reaction times are faster in HIV-seropositive patients on antiretroviral therapy: a preliminary report. Journal of Clinical and Experimental Neuropsychology, 5, 730735.Google Scholar
Meador, K.J. (2001). Cognitive effects of epilepsy and of antiepileptic medications. In: Wyllie, E. (ed.), The Treatment of Epilepsy: Principles and Practice (3rd ed.). Philadelphia: Lippincott Williams & Wilkins, pp. 12151225.
Meador, K.J. (1998). Cognitive and behavioural assessments in AED trials. Antiepileptic Drug Development: Advances in Neurology, 76, 231238.Google Scholar
Meador, K., Loring, D.W., Ray, P.G., et al. (2001). Differential cognitive and behavioural effects of carbamazepine and lamotrigine. Neurology, 56, 11771182.Google Scholar
Meador, K.J., Loring, D.W., Abney, O.L., et al. (1993). Effects of carbamazepine and phenytoin on EEG and memory in healthy adults. Epilepsia, 34, 153157.Google Scholar
Meador, K.J., Loring, D.W., Allen, M.E., et al. (1991). Comparative cognitive effects of carbamazepine and phenytoin in healthy adults. Neurology, 41, 15371540.Google Scholar
Miller, E.N. (1992). Use of computerized reaction time in the assessment of dementia (abstract). Neurology, 42, 220.Google Scholar
Miller, E.N. (1980). California Computerized Assessment Battery (CalCAP) Manual. Los Angeles: Norland Software.
Miller, E.N., Satz, P., & Visscher, B. (1991). Computerized and conventional neuropsychological assessment of HIV-1 infected homosexual men. Neurology, 41, 16081616.Google Scholar
Miller, E.N., Satz, P., & Visscher, B. (1989). Computerized neuropsychological assessment for HIV-related encephalopathy. Symposium on novel and traditional approaches for early detection of HIV-1 related dementia (Vancouver, Canada). Journal of Clinical and Experimental Neuropsychology, 11, 3435.Google Scholar
Prevey, M.L., Delaney, R.C., Cramer, J.A., et al. (1996). Effect of valproate on cognitive function: comparison with carbamazepine: the Department of Veterans Affairs Epilepsy Cooperative Study 264 Group. Archives of Neurology, 53, 10081016.Google Scholar
Sillanpaa, A., & Schmidt, D. (2006). Prognosis of seizure recurrence after stopping antiepileptic drugs in seizure-free patients: a long-term population based study of childhood-onset epilepsy. Epilepsy & Behavior, 8, 713719.Google Scholar
Specchio, L.M., & Beghi, E. (2004). Should antiepileptic drugs be withdrawn in seizure-free patients? Drugs, 18, 201212.Google Scholar
Thompson, P.J., & Trimble, M.R. (1981). Sodium valproate and cognitive function in normal volunteers. British Journal of Clinical Pharmacology, 12, 819824.Google Scholar
Vermeulen, J., & Aldenkamp, A.P. (1995). Cognitive side-effects of chronic antiepileptic drug treatment: a review of 25 years of research. Epilepsy Research, 22, 6595.Google Scholar
Worth, J.L., Savage, C.R., Baer, L., Esty, E.K., & Navia, B.A. (1993). Computer-based neuropsychological screening for AIDS dementia complex. AIDS, 7, 677681.Google Scholar