Abstract
Topiramate (TPM) is a sulfamate-substituted monosaccharide with multiple putative mechanisms of action, including voltage-gated sodium channels, high-voltage-activated calcium channels, GABA-A receptors, AMPA/kainate receptors, and carbonic anhydrase isoenzymes. TPM has proven to be effective through a wide series of trials in monotherapy and add-on therapy in focal epilepsies in adults and children. TPM is also effective in epilepsy with generalized seizures and may help in some epileptic encephalopathies such as Lennox-Gastaut and Dravet Syndromes. Good efficacy with fare tolerability and a relatively safe profile is obtained at doses of 100–200 mg/day in adults and ~3.5 mg/kg/day in children. Slow titration of TPM to a low-medium dosage will enhance tolerability. Furthermore, long-term follow-up studies indicate that the response to TPM is durable. Known interactions with other drugs are modest and rarely of clinical significance, apart from mild induction on estroprogestative contraceptive drugs. Note however that the association of TPM with valproate may induce encephalopathy with hyperammonemia. One major limitation of TPM-treatment is cognitive side effects (such as slowing in verbal fluency) as well as paresthesia, depression, and significant weight loss, notably in adult patients. TPM also increases the risk of nephrolithiasis, acidosis, and vision disturbances. During pregnancy, TPM conveys a significantly higher risk of major malformations as other antiepileptic drugs (AEDs) such as Lamotrigine and Levetiracetam and is therefore of limited use in women of childbearing age.
In sum, even if TPM offers a valid therapeutic option in a wide spectrum of seizures, its safety profile should be individually monitored. The most suitable indications for use of TPM are patients suffering from both focal seizures and migraine comorbidity as well as children with Dravet syndrome.
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References
Arroyo S, Dodson W, Privitera MD, et al. Randomized dose controlled study of Topiramate in Epilepsy. Acta Neurologica Scandinavica. 2005;
Ben-Menachem E. Weight issues for people with epilepsy – a review. Epilepsia. 2007;48(Suppl 9):42–5.
Ben-Menachem E, Sander JW, Stefan H, Schwalen S, Schäuble B. Topiramate monotherapy in the treatment of newly or recently diagnosed epilepsy. Clin Ther. 2008 Jul;30(7):1180–95.
Bialer M, Shekh-Ahmad T, Braun TL, Halvorsen MB. Comparative steady-state pharmacokinetic evaluation of immediate-release topiramate and USL255, a once-daily extended-release topiramate formulation. Epilepsia. 2013 Aug;54(8):1444–52.
Biton V, Montouris GD, Ritter F, Riviello JJ, Reife R, Lim P, Pledger G. A randomized, placebo-controlled study of topiramate in primary generalized tonic-clonic seizures. Topiramate YTC Study Group. Neurology. 1999;52:1330–7.
Bromley RL, Calderbank R, Cheyne CP, Rooney C, Trayner P, Clayton-Smith J, García-Fiñana M, Irwin B, Morrow JI, Shallcross R, Baker GA, UK Epilepsy and Pregnancy Register. Cognition in school-age children exposed to levetiracetam, topiramate, or sodium valproate. Neurology. 2016;87(18):1943–53.
Dell’Orto VG, Belotti EA, Goeggel-Simonetti B, Simonetti GD, Ramelli GP, Bianchetti MG, Lava SA. Metabolic disturbances and renal stone promotion on treatment with topiramate: a systematic review. Br J Clin Pharmacol. 2014;77(6):958–64.
Elterman RD, Glauser TA, Wyllie E, Reife R, Wu SC, Pledger G. A double-blind, randomized trial of topiramate as adjunctive therapy for partial-onset seizures in children. Topiramate YP Study Group. Neurology. 1999;52:1338–44.
Ford L, Goldberg JL, Selan F, Greenberg HE, Shi Y. Comprehensive review of visual defects reported with topiramate. Clin Ophthalmol. 2017;11:983–92.
Gilliam FG, Veloso F, Bomhof MA, et al. A dose-comparison trial of topiramate as monotherapy in recently diagnosed partial epilepsy. Neurology. 2003;60:196–202.
Guberman A, Neto W, Gassmann-Mayer C, EPAJ-119 Study Group. Low-dose topiramate in adults with treatment resistant partial-onset seizures. Acta Neurol Scand. 2002;106:183–9.
Guerrini R, Carpay J, Groselj J, van Oene J, Schreiner A, Lahaye M, Schwalen S, TOP-INT-51 Investigators’ Group. Topiramate monotherapy as broad-spectrum antiepileptic drug in a naturalistic clinical setting. Seizure. 2005;14(6):371–80.
Hernandez-Diaz S, Huybrechts KF, Desai RJ, Cohen JM, Mogun H, Pennell PB, Bateman BT, Patorno E. Topiramate use early in pregnancy and the risk of oral clefts: a pregnancy cohort study. Neurology. 2018;90(4):e342–51.
Herrero AI, Del Olmoa N, Gonzalez-Escaladab JR, Solis JM. Two new actions of topiramate: inhibition of depolarizing GABAA-mediated responses and activation of a potassium conductance. Neuropharmacology. 2002;42:210–20.
Johnston CA, Crawford PM. Anti-epileptic drugs and hormonal treatments. Curr Treat Options Neurol. 2014;16(5):288.
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(2-3):171–8.
Lee SK, Lee SA, Kim DW, Loesch C, Pelgrims B, Osakabe T, Lee B. N01353 study group. A randomized, open-label, multicenter comparative trial of levetiracetam and topiramate as adjunctive treatment for patients with focal epilepsy in Korea. Epilepsy Behav. 2019;97:67–74. https://doi.org/10.1016/j.yebeh.2019.05.014. Epub 2019 Jun 10. PMID: 31195326.
Loring DW, Williamson DJ, Meador KJ, Wiegand F, Hulihan J. Topiramate dose effects on cognition: a randomized double-blind study. Neurology. 2011;76(2):131–7.
Marino SE, Pakhomov SV, Han S, Anderson KL, Ding M, Eberly LE, Loring DW, Hawkins-Taylor C, Rarick JO, Leppik IE, Cibula JE, Birnbaum AK. The effect of topiramate plasma concentration on linguistic behavior, verbal recall and working memory. Epilepsy Behav. 2012;24(3):365–72.
Maryanoff BE. Phenotypic assessment and the discovery of topiramate. ACS MedChem Lett. 2016;7(7):662–5.
Meador KJ, Penovich P, Baker GA, Pennell PB, Bromfield E, Pack A, Liporace JD, Sam M, Kalayjian LA, Thurman DJ, Moore E, Loring DW, NEAD Study Group. Antiepileptic drug use in women of childbearing age. Epilepsy Behav. 2009a;15(3):339–43.
Meador KJ, Baker GA, Browning N, Clayton-Smith J, Combs-Cantrell DT, Cohen M, Kalayjian LA, Kanner A, Liporace JD, Pennell PB, Privitera M, Loring DW, NEAD Study Group. Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs. N Engl J Med. 2009b;360(16):1597–605.
Morimoto M, Shimakawa S, Hashimoto T, Kitaoka T, Kyotani S. Marked efficacy of combined three-drug therapy (Sodium Valproate, Topiramate and Stiripentol) in a patient with Dravet syndrome. J Clin Pharm Ther. 2018;43(4):571–3.
Mula M. Topiramate and cognitive impairment: evidence and clinical implications. Ther Adv Drug Saf. 2012;3(6):279–89.
Mula M, Trimble MR, Lhatoo SD, Sander JW. Topiramate and psychiatric adverse events in patients with epilepsy. Epilepsia. 2003;44(5):659–63.
O’Neal W, Hur EE, Liranso T, Patel B. Real-world assessment of treatment with extended-release topiramate (Trokendi XR(®)) and comparison with previous immediate-release topiramate treatment. J Comp Eff Res. 2018;7(11):1095–105.
Perucca E. Marketed new antiepileptic drugs: are they better than old-generation agents? Ther Drug Monit. 2002;24(1):74–80.
Pigott K, Galizia I, Vasudev K, Watson S, Geddes J, Young AH. Topiramate for acute affective episodes in bipolar disorder in adults. Cochrane Database Syst Rev. 2016;9:CD003384.
Privitera MD, Brodie MJ, Mattson RH, Chadwick DW, Neto W, Wang S. EPMN 105 Study Group. Topiramate, carbamazepine and valproate monotherapy: double-blind comparison in newly diagnosed epilepsy. Acta Neurol Scand. 2003;107(3):165–75. https://doi.org/10.1034/j.1600-0404.2003.00093.x. PMID: 12614309.
Reife RA, Pledger GW. Topiramate as adjunctive therapy in refractory partial epilepsy: pooled analysis of data from five double-blind, placebo-controlled trials. Epilepsia. 1997;38(Suppl 1):S31–3. https://doi.org/10.1111/j.1528-1157.1997.tb04515.x.
Reife RA, Pledger G, Wu SC. Topiramate as add-on therapy: pooled analysis of randomized controlled trials in adults. Epilepsia. 2000;41(Suppl 1):S66–71.
Sachdeo RC, Reife RA, Lim P, Pledger G. Topiramate monotherapy for partial onset seizures. Epilepsia. 1997;38:294–300.
Sachdeo RC, Glauser TA, Ritter F, et al. A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Topiramate YL Study Group. Neurology. 1999;52:1882–7.
Sciegienka A, Argo T, Cantrell M, Alexander B. Association between topiramate use and serum bicarbonate levels in a veteran population. Ann Pharmacother. 2015;49(6):670–3.
Sedighi B, Shafiei K, Azizpour I. Topiramate-induced paresthesia is more frequently reported by migraine than epileptic patients. Neurol Sci. 2016;37(4):585–9. https://doi.org/10.1007/s10072-015-2458-9.
Shank RP, Gardocki JF, Streeter AJ, Maryanoff BE. An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia. 2000;41(Suppl 1):S3–9.
Smith SM, Meyer M, Trinkley KE. Phentermine/topiramate for the treatment of obesity. Ann Pharmacother. 2013;47(3):340–9. https://doi.org/10.1345/aph.1R501.
Spritzer SD, Bravo TP, Drazkowski JF. Topiramate for treatment in patients with migraine and epilepsy. Headache. 2016;56(6):1081–5.
Tatum WO 4th, Galvez R, Benbadis S, Carrazana E. New antiepileptic drugs: into the new millennium. Arch Fam Med. 2000;9(10):1135–41.
Türe H, Keskin Ö, Çakır Ü, Aykut Bingöl C, Türe U. The frequency and severity of metabolic acidosis related to topiramate. J Int Med Res. 2016;44(6):1376–80.
Verrotti A, Scaparrotta A, Agostinelli AS, Di Pillo S, Chiarelli F, Grosso S. Topiramate-induced weight loss: a review. Epilepsy Res. 2011;5(3):189–99.
Wandschneider B, Burdett J, Townsend L, Hill A, Thompson PJ, Duncan JS, Koepp MJ. Effect of topiramate and zonisamide on fMRI cognitive networks. Neurology. 2017;88(12):1165–71.
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Dinkelacker, V., Valenti, M.P., Hirsch, E. (2022). Anti-convulsant Agents: Topiramate. In: Riederer, P., Laux, G., Nagatsu, T., Le, W., Riederer, C. (eds) NeuroPsychopharmacotherapy. Springer, Cham. https://doi.org/10.1007/978-3-030-62059-2_308
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