Neuropsychological side effects of anti-epileptic drugs in epilepsy patients: a cross sectional study
Keywords:Antiepileptic drug, Cognition, Epilepsy, Neuropsychological side effects
Background: Epilepsy is the fourth most common neurological disorder in world. Managing an epilepsy with anti-epileptic drugs (AEDs) either as monotherapy or polytherapy is necessary to reduce the deleterious effect of the disease and to provide neuroprotection. AEDs exert their negative effects on cognition by suppressing neuronal excitability or enhancing inhibitory neurotransmission. These neuropsychological side effects are found to be modest when the drug level is within the therapeutic concentration and used as monotherapy. Objectives were to assess the prevalence of neuropsychological side effects among epilepsy patients who were on antiepileptic drug therapy.
Methods: An open label, cross-sectional, clinical study was conducted at a tertiary care hospital, 126 participants were recruited. Participants demographic data, detailed medical and seizure history followed by neuropsychological tests was performed. The prevalence was assessed based on the number of participants scoring <15th percentile in one or more tests.
Results: Out of 126 participants who were recruited, 82 participants were on monotherapy and 44 participants were on polytherapy. Levetiracetam was the most commonly prescribed drug as monotherapy, followed by phenytoin, carbamazepine and valproate; whereas in polytherapy levetiracetam, clobazam followed by phenytoin were the commonly prescribed AED. The most common adverse effect was drowsiness, followed by headache, hypersensitivity reaction, giddiness, tremors, anxiety etc. The prevalence of neuropsychological side effects was 77.8%. The prevalence of impairment between monotherapy and polytherapy was statistically insignificant (p=0.727).
Conclusions: In this study, levetiracetam was the most commonly prescribed drug and the most common adverse effect was drowsiness due to AEDs. The subgroup analyses between monotherapy and polytherapy did not show any statistically significant neuropsychological impairment when compared based on the gender, age groups, duration of epilepsy with medication and duration of current therapy.
Porter RJ, Rogawski MA. Antiseizure Drugs. In: Katzung BG, editor. Basic and Clinical Pharmacology. 14th edition. New York: McGraw-Hill Education. 2018;409-39.
Sharma HL, Sharma KK. Sharma and Sharma’s Principles of pharmacology. 3rd edition. Hyderabad: Paras Medical Publisher. 2017;523-38.
Kwan P, Brodie MJ. Neuropsychological effects of epilepsy and antiepileptic drugs. Lancet. 2001;357(9251):216-22.
Garrard J, Harms S, Hardie N, Eberly LE, Nitz N, Bland P et al. Antiepileptic drug use in nursing home admissions. Ann Neurol. 2003;54:75-85.
Holmes GL. Epilepsy in the developing brain: lessons from the laboratory and clinic. Epilepsia. 1997;38:12-30.
Rao SL, Subbakrishna DK, Gopukumar K. NIMHANS Neuropsychological Battery Manual. Bangalore: NIMHANS Publications. 2004.
Cochrane H, Marson A, Baker G, Chadwick D. Neuropsychological Outcomes in Randomized Controlled Trials of Antiepileptic Drugs: A Systematic Review of Methodology and Reporting Standards. Epilepsia. 1998;39(10):1088-97.
Tanner-Eggen C, Balzer C, Perrig W, Gutbrod K. The Neuropsychological Assessment of Cognitive Deficits Considering Measures of Performance Variability. Arch Clin Neuropsychol. 2015;30(3):217-27.
Ortinski P, Meador K. Cognitive side effects of antiepileptic drugs. Epilepsy Behavior. 2004;5:S60-65.
Hamed SA. The Aspects and Mechanisms of Cognitive Alterations in Epilepsy: The Role of Antiepileptic Medications. CNS Neurosci Therapeutics. 2009;15(2):134-56.
Rybakowski J. Leki normotymiczne. Terapia. 2004;12:12-7.
Piazzini A, Chifari R, Canevini MP, Turner K, Fontana SP, Canger R. Levetiracetam: An improvement of attention and of oral fluency in patients with partial epilepsy. Epilepsy Res. 2006;68:181-8.
Koo D, Hwang K, Kim D, Kim Y, Kim J, Shin W et al. Effects of Levetiracetam Monotherapy on the Cognitive Function of Epilepsy Patients. European Neurol. 2013;70(1-2):88-94.
Helmstaedter C, Witt JA. The effects of levetiracetam on cognition: A non-interventional surveillance study. Epilepsy Behav. 2008;13:642-9.
Zhou B, Zhang Q, Tian L, Xiao J, Stefan H, Zhou D. Effects of levetiracetam as an add-on therapy on cognitive function and quality of life in patients with refractory partial seizures. Epilepsy Behav. 2008;12:305-10.
Brooks B, Iverson G, Lanting S, Horton A, Reynolds C. Improving Test Interpretation for Detecting Executive Dysfunction in Adults and Older Adults: Prevalence of Low Scores on the Test of Verbal Conceptualization and Fluency. Applied Neuropsychol Adult. 2012;19(1):61-70.