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Published in: CNS Drugs 12/2022

Open Access 01-12-2022 | Epilepsy | Original Research Article

Evaluation of a Rapid Topiramate Titration Scheme for the Early Detection of Cognitive Side Effects

Authors: Juri-Alexander Witt, Guido Widman, Niels Hansen, Randi von Wrede, Christian E. Elger, Christoph Helmstaedter

Published in: CNS Drugs | Issue 12/2022

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Abstract

Background

Topiramate (TPM) is effective for treating epilepsy, but executive dysfunction is a common side effect that could significantly affect everyday life. Additionally, previous studies have suggested that patients might be unaware of these changes.

Objective

To evaluate a rapid TPM titration scheme for the early detection of adverse cognitive side effects.

Methods

In this retrospective study, we assessed changes in objective cognitive performance (EpiTrack®) after rapidly titrating TPM (50 mg per day during an inpatient stay) in 49 epilepsy patients and compared those results with an outpatient control group that underwent the recommended standard titration (n = 23 with 25–50 mg per week).

Results

Using Bayesian statistics, analyses revealed decisive evidence of a negative effect on cognitive performance when TPM was introduced (BF 31480000000) independent of the titration speed (BF 0.739). When using a fast titration rate, deficits in executive function increased from a baseline of 53.1 to 73.5% at follow-up, and 55.1% experienced a statistically significant intraindividual decline. When using the standard titration scheme, impairments increased from 52.2 to 65.2%, with an intraindividual deterioration found in 52.2% of the patients.

Conclusion

Physicians might be able to detect adverse cognitive side effects sooner in epilepsy patients if TPM is administered using a faster titration rate while applying repeated cognitive assessments within days. This approach might help prevent any unnoticed intolerance and eventual negative consequences for the patient. Therefore, we recommend monitoring early on for adverse changes instead of withholding a potentially effective treatment option because of anticipated side effects.
Literature
1.
go back to reference Lyseng-Williamson KA, Yang LPH. Topiramate: a review of its use in the treatment of epilepsy. Drugs. 2007;67:2231–56.CrossRefPubMed Lyseng-Williamson KA, Yang LPH. Topiramate: a review of its use in the treatment of epilepsy. Drugs. 2007;67:2231–56.CrossRefPubMed
2.
go back to reference Silberstein S, Diener HC, Lipton R, Goadsby P, Dodick D, Bussone G, et al. Epidemiology, risk factors, and treatment of chronic migraine: a focus on topiramate. Headache. 2008;48:1087–95.CrossRefPubMed Silberstein S, Diener HC, Lipton R, Goadsby P, Dodick D, Bussone G, et al. Epidemiology, risk factors, and treatment of chronic migraine: a focus on topiramate. Headache. 2008;48:1087–95.CrossRefPubMed
3.
go back to reference Astrup A, Toubro S. Topiramate: a new potential pharmacological treatment for obesity. Obes Res. 2004;12(Suppl):167S-S173.CrossRefPubMed Astrup A, Toubro S. Topiramate: a new potential pharmacological treatment for obesity. Obes Res. 2004;12(Suppl):167S-S173.CrossRefPubMed
4.
go back to reference Nazarbaghi S, Amiri-Nikpour MR, Eghbal AF, Valizadeh R. Comparison of the effect of topiramate versus gabapentin on neuropathic pain in patients with polyneuropathy: a randomized clinical trial. Electron physician. 2017;9:5617–22.CrossRefPubMedPubMedCentral Nazarbaghi S, Amiri-Nikpour MR, Eghbal AF, Valizadeh R. Comparison of the effect of topiramate versus gabapentin on neuropathic pain in patients with polyneuropathy: a randomized clinical trial. Electron physician. 2017;9:5617–22.CrossRefPubMedPubMedCentral
5.
go back to reference Guglielmo R, Martinotti G, Quatrale M, Ioime L, Kadilli I, Di Nicola M, et al. Topiramate in alcohol use disorders: review and update. CNS Drugs. 2015;29:383–95.CrossRefPubMed Guglielmo R, Martinotti G, Quatrale M, Ioime L, Kadilli I, Di Nicola M, et al. Topiramate in alcohol use disorders: review and update. CNS Drugs. 2015;29:383–95.CrossRefPubMed
6.
go back to reference Scholten J, Hamer HM, Kostev K. Usage of antiepileptic drugs in different diseases in Germany—a retrospective study. Epilepsy Behav. 2020;111: 107210.CrossRefPubMed Scholten J, Hamer HM, Kostev K. Usage of antiepileptic drugs in different diseases in Germany—a retrospective study. Epilepsy Behav. 2020;111: 107210.CrossRefPubMed
7.
go back to reference Kockelmann E, Elger CE, Helmstaedter C. Cognitive profile of topiramate as compared with lamotrigine in epilepsy patients on antiepileptic drug polytherapy: relationships to blood serum levels and comedication. Epilepsy Behav. 2004;5:716–21.CrossRefPubMed Kockelmann E, Elger CE, Helmstaedter C. Cognitive profile of topiramate as compared with lamotrigine in epilepsy patients on antiepileptic drug polytherapy: relationships to blood serum levels and comedication. Epilepsy Behav. 2004;5:716–21.CrossRefPubMed
8.
go back to reference Meschede C, Witt JA, Brömling S, Moskau-Hartmann S, Rademacher M, Surges R, et al. Changes in cognition after introduction or withdrawal of zonisamide versus topiramate in epilepsy patients: a retrospective study using Bayes statistics. Epilepsia. 2020;61:1481–90.CrossRefPubMed Meschede C, Witt JA, Brömling S, Moskau-Hartmann S, Rademacher M, Surges R, et al. Changes in cognition after introduction or withdrawal of zonisamide versus topiramate in epilepsy patients: a retrospective study using Bayes statistics. Epilepsia. 2020;61:1481–90.CrossRefPubMed
9.
go back to reference Witt J-A, Elger CE, Helmstaedter C. Which drug-induced side effects would be tolerated in the prospect of seizure control? Epilepsy Behav. 2013;29:141–3.CrossRefPubMed Witt J-A, Elger CE, Helmstaedter C. Which drug-induced side effects would be tolerated in the prospect of seizure control? Epilepsy Behav. 2013;29:141–3.CrossRefPubMed
10.
go back to reference Jansen JFA, Aldenkamp AP, Marian Majoie HJ, Reijs RP, de Krom MCTFM, Hofman PAM, et al. Functional MRI reveals declined prefrontal cortex activation in patients with epilepsy on topiramate therapy. Epilepsy Behav. 2006;9:181–5.CrossRefPubMed Jansen JFA, Aldenkamp AP, Marian Majoie HJ, Reijs RP, de Krom MCTFM, Hofman PAM, et al. Functional MRI reveals declined prefrontal cortex activation in patients with epilepsy on topiramate therapy. Epilepsy Behav. 2006;9:181–5.CrossRefPubMed
11.
go back to reference Witt JA, Rademacher M, von Wrede R, Surges R, Helmstaedter C. Cognitive reawakening and improved quality of life achieved after discontinuing 16 years of anti-seizure treatment with topiramate. Neurocase. 2022;28:102–6.CrossRefPubMed Witt JA, Rademacher M, von Wrede R, Surges R, Helmstaedter C. Cognitive reawakening and improved quality of life achieved after discontinuing 16 years of anti-seizure treatment with topiramate. Neurocase. 2022;28:102–6.CrossRefPubMed
12.
go back to reference Huppertz HJ, Quiske A, Schulze-Bonhage A. Kognitive Beeinträchtigungen unter Add-on-Therapie mit Topiramat. Nervenarzt. 2001;72:275–80.CrossRefPubMed Huppertz HJ, Quiske A, Schulze-Bonhage A. Kognitive Beeinträchtigungen unter Add-on-Therapie mit Topiramat. Nervenarzt. 2001;72:275–80.CrossRefPubMed
13.
go back to reference Javed A, Cohen B, Detyniecki K, Hirsch LJ, Legge A, Chen B, et al. Rates and predictors of patient-reported cognitive side effects of antiepileptic drugs: an extended follow-up. Seizure. 2015;29:34–40.CrossRefPubMed Javed A, Cohen B, Detyniecki K, Hirsch LJ, Legge A, Chen B, et al. Rates and predictors of patient-reported cognitive side effects of antiepileptic drugs: an extended follow-up. Seizure. 2015;29:34–40.CrossRefPubMed
14.
go back to reference Aldenkamp AP, Baker G, Mulder OG, Chadwick D, Cooper P, Doelman J, 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 partial-onset seizures. Epilepsia. 2000;41:1167–78.CrossRefPubMed Aldenkamp AP, Baker G, Mulder OG, Chadwick D, Cooper P, Doelman J, 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 partial-onset seizures. Epilepsia. 2000;41:1167–78.CrossRefPubMed
15.
go back to reference Gomer B, Wagner K, Frings L, Saar J, Carius A, Härle M, et al. The influence of antiepileptic drugs on cognition: a comparison of levetiracetam with topiramate. Epilepsy Behav. 2007;10:486–94.CrossRefPubMed Gomer B, Wagner K, Frings L, Saar J, Carius A, Härle M, et al. The influence of antiepileptic drugs on cognition: a comparison of levetiracetam with topiramate. Epilepsy Behav. 2007;10:486–94.CrossRefPubMed
16.
go back to reference Salinsky MC, Storzbach D, Spencer DC, Oken BS, Landry T, Dodrill CB. Effects of topiramate and gabapentin on cognitive abilities in healthy volunteers. Neurology. 2005;64:792–8.CrossRefPubMed Salinsky MC, Storzbach D, Spencer DC, Oken BS, Landry T, Dodrill CB. Effects of topiramate and gabapentin on cognitive abilities in healthy volunteers. Neurology. 2005;64:792–8.CrossRefPubMed
17.
go back to reference Kockelmann E, Elger CE, Helmstaedter C. Significant improvement in frontal lobe associated neuropsychological functions after withdrawal of topiramate in epilepsy patients. Epilepsy Res. 2003;54:171–8.CrossRefPubMed Kockelmann E, Elger CE, Helmstaedter C. Significant improvement in frontal lobe associated neuropsychological functions after withdrawal of topiramate in epilepsy patients. Epilepsy Res. 2003;54:171–8.CrossRefPubMed
18.
go back to reference Fritz N, Glogau S, Hoffmann J, Rademacher M, Elger CE, Helmstaedter C. Efficacy and cognitive side effects of tiagabine and topiramate in patients with epilepsy. Epilepsy Behav. 2005;6:373–81.CrossRefPubMed Fritz N, Glogau S, Hoffmann J, Rademacher M, Elger CE, Helmstaedter C. Efficacy and cognitive side effects of tiagabine and topiramate in patients with epilepsy. Epilepsy Behav. 2005;6:373–81.CrossRefPubMed
19.
go back to reference Romigi A, Cervellino A, Marciani MG, Izzi F, Massoud R, Corona M, et al. Cognitive and psychiatric effects of topiramate monotherapy in migraine treatment: an open study. Eur J Neurol. 2008;15:190–5.CrossRefPubMed Romigi A, Cervellino A, Marciani MG, Izzi F, Massoud R, Corona M, et al. Cognitive and psychiatric effects of topiramate monotherapy in migraine treatment: an open study. Eur J Neurol. 2008;15:190–5.CrossRefPubMed
20.
go back to reference Witt J-A, Helmstaedter C. How can we overcome neuropsychological adverse effects of antiepileptic drugs? Expert Opin Pharmacother. 2017;18:1–4.CrossRef Witt J-A, Helmstaedter C. How can we overcome neuropsychological adverse effects of antiepileptic drugs? Expert Opin Pharmacother. 2017;18:1–4.CrossRef
21.
go back to reference Witt J-A, Helmstaedter C. Monitoring the cognitive effects of antiepileptic pharmacotherapy—approaching the individual patient. Epilepsy Behav. 2013;26:450–6.CrossRefPubMed Witt J-A, Helmstaedter C. Monitoring the cognitive effects of antiepileptic pharmacotherapy—approaching the individual patient. Epilepsy Behav. 2013;26:450–6.CrossRefPubMed
22.
go back to reference Widman G, Witt J-A, Elger CE, Helmstaedter C. Does fast titration of topiramate reveal the early detection of patients who will experience negative cognitive side effects? [poster]. Eur J Neurol. 2015;22:338. Widman G, Witt J-A, Elger CE, Helmstaedter C. Does fast titration of topiramate reveal the early detection of patients who will experience negative cognitive side effects? [poster]. Eur J Neurol. 2015;22:338.
23.
go back to reference Lutz MT, Helmstaedter C. EpiTrack: tracking cognitive side effects of medication on attention and executive functions in patients with epilepsy. Epilepsy Behav. 2005;7:708–14.CrossRefPubMed Lutz MT, Helmstaedter C. EpiTrack: tracking cognitive side effects of medication on attention and executive functions in patients with epilepsy. Epilepsy Behav. 2005;7:708–14.CrossRefPubMed
25.
go back to reference Meschede C, Witt J, Rademacher M, Von WRD, Elger CE, Helmstaedter C. Evaluating the longer-term cognitive effects of adjunctive perampanel compared to lacosamide in a naturalistic outpatient setting. Seizure Eur J Epilepsy. 2018;58:141–6.CrossRef Meschede C, Witt J, Rademacher M, Von WRD, Elger CE, Helmstaedter C. Evaluating the longer-term cognitive effects of adjunctive perampanel compared to lacosamide in a naturalistic outpatient setting. Seizure Eur J Epilepsy. 2018;58:141–6.CrossRef
26.
go back to reference Helmstaedter C, Witt J-A. The longer-term cognitive effects of adjunctive antiepileptic treatment with lacosamide in comparison with lamotrigine and topiramate in a naturalistic outpatient setting. Epilepsy Behav. 2013;26:182–7.CrossRefPubMed Helmstaedter C, Witt J-A. The longer-term cognitive effects of adjunctive antiepileptic treatment with lacosamide in comparison with lamotrigine and topiramate in a naturalistic outpatient setting. Epilepsy Behav. 2013;26:182–7.CrossRefPubMed
27.
go back to reference Helmstaedter C, Witt J-A. Cognitive outcome of antiepileptic treatment with levetiracetam versus carbamazepine monotherapy: a non-interventional surveillance trial. Epilepsy Behav. 2010;18:74–80.CrossRefPubMed Helmstaedter C, Witt J-A. Cognitive outcome of antiepileptic treatment with levetiracetam versus carbamazepine monotherapy: a non-interventional surveillance trial. Epilepsy Behav. 2010;18:74–80.CrossRefPubMed
28.
go back to reference Helmstaedter C, Witt J-A. The effects of levetiracetam on cognition: a non-interventional surveillance study. Epilepsy Behav. 2008;13:642–9.CrossRefPubMed Helmstaedter C, Witt J-A. The effects of levetiracetam on cognition: a non-interventional surveillance study. Epilepsy Behav. 2008;13:642–9.CrossRefPubMed
29.
go back to reference Witt J-A, Elger CE, Helmstaedter C. Short-term and longer-term effects of brivaracetam on cognition and behavior in a naturalistic clinical setting—preliminary data. Seizure. 2018;62:49–54.CrossRefPubMed Witt J-A, Elger CE, Helmstaedter C. Short-term and longer-term effects of brivaracetam on cognition and behavior in a naturalistic clinical setting—preliminary data. Seizure. 2018;62:49–54.CrossRefPubMed
30.
go back to reference Witt J-A, Elger CE, Helmstaedter C. Adverse cognitive effects of antiepileptic pharmacotherapy: Each additional drug matters. Eur Neuropsychopharmacol. 2015;25:1954–9.CrossRefPubMed Witt J-A, Elger CE, Helmstaedter C. Adverse cognitive effects of antiepileptic pharmacotherapy: Each additional drug matters. Eur Neuropsychopharmacol. 2015;25:1954–9.CrossRefPubMed
31.
go back to reference Helmstaedter C, Elger CE, Witt JA. The effect of quantitative and qualitative antiepileptic drug changes on cognitive recovery after epilepsy surgery. Seizure. 2016;36:63–9.CrossRefPubMed Helmstaedter C, Elger CE, Witt JA. The effect of quantitative and qualitative antiepileptic drug changes on cognitive recovery after epilepsy surgery. Seizure. 2016;36:63–9.CrossRefPubMed
32.
go back to reference Etz A, Gronau QF, Dablander F, Edelsbrunner PA, Baribault B. How to become a Bayesian in eight easy steps: an annotated reading list. Psychon Bull Rev. 2018;25:219–34.CrossRefPubMed Etz A, Gronau QF, Dablander F, Edelsbrunner PA, Baribault B. How to become a Bayesian in eight easy steps: an annotated reading list. Psychon Bull Rev. 2018;25:219–34.CrossRefPubMed
Metadata
Title
Evaluation of a Rapid Topiramate Titration Scheme for the Early Detection of Cognitive Side Effects
Authors
Juri-Alexander Witt
Guido Widman
Niels Hansen
Randi von Wrede
Christian E. Elger
Christoph Helmstaedter
Publication date
01-12-2022
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 12/2022
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.1007/s40263-022-00969-3

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