A viewpoint on rational and irrational fixed-drug combinations

References

• Kerr MP. The impact of epilepsy on patients’ lives. Acta Neurol Scand Suppl. 2012;194:1–9.
   Google Scholar
• Duncan JS, Sander JW, Sisodiya SM, et al. Adult epilepsy. Lancet. 2006;367:1087–1100.
   PubMed Web of Science ®Google Scholar
• Fisher RS. The new classification of seizures by the International League Against Epilepsy 2017. Curr Neurol Neurosci Rep. 2017;17(6):48.
   PubMed Web of Science ®Google Scholar
• Blumenfeld H, Jackson GD. Should consciousness be included in the classification of focal (partial) seizures? Epilepsia. 2013;54(6):1125–1130.
   PubMed Web of Science ®Google Scholar
• Cavanna AE, Monaco F. Brain mechanisms of altered conscious state during epileptic seizures. Nat Rev Neurol. 2009;5(5):267–276.
   PubMed Web of Science ®Google Scholar
• Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia. 2010;51(4):676–685.
   PubMed Web of Science ®Google Scholar
• Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342(5):314–319.
   PubMed Web of Science ®Google Scholar
• Brodie MJ, Barry SJ, Bamagous GA, et al. Patterns of treatment response in newly diagnosed epilepsy. Neurology. 2012;78(20):1548–1554.
   PubMed Web of Science ®Google Scholar
• Ben-Menachem E, Sander JW, Privitera M, et al. Measuring outcomes of treatment with antiepileptic drugs in clinical trials. Epilepsy Behav. 2010;18(1–2):24–30.
   PubMed Web of Science ®Google Scholar
• Deckers CL. Place of polytherapy in the early treatment of epilepsy. CNS Drugs. 2002;16(3):155–163.
   PubMed Web of Science ®Google Scholar
• St Louis EK. Truly rational polytherapy: maximizing efficacy and minimizing drug interactions, drug load, and adverse effects. Curr Neuropharmacol. 2009;7(2):96–105.
   PubMed Web of Science ®Google Scholar
• Kwan P, Brodie MJ. Epilepsy after the first drug fails: substitution or add-on? Seizure. 2000;9(7):464–468.
   PubMed Web of Science ®Google Scholar
• Beghi E, Gatti G, Tonini C, et al. Adjunctive therapy versus alternative monotherapy in patients with partial epilepsy failing on a single drug: a multicentre, randomised, pragmatic controlled trial. Epilepsy Res. 2003;57(1):1–13.
   PubMed Web of Science ®Google Scholar
• Millul A, Iudice A, Adami M, et al. Alternative monotherapy or add-on therapy in patients with epilepsy whose seizures do not respond to the first monotherapy: an Italian multicenter prospective observational study. Epilepsy Behav. 2013;28(3):494–500.
   PubMed Web of Science ®Google Scholar
• Semah F, Thomas P, Coulbaut S, et al. Early add-on treatment vs alternative monotherapy in patients with partial epilepsy. Epileptic Disord. 2014;16(2):165–174.
   PubMed Web of Science ®Google Scholar
• Abou-Khalil B. Selecting rational drug combinations in epilepsy. CNS Drugs. 2017;31(10):835–844.
   PubMed Web of Science ®Google Scholar
• Deckers CL, Czuczwar SJ, Hekster YA, et al. Selection of antiepileptic drug polytherapy based on mechanisms of action: the evidence reviewed. Epilepsia. 2000;41(11):1364–1374.
   PubMed Web of Science ®Google Scholar
• Jonker DM, Voskuyl RA, Danhof M. Synergistic combinations of anticonvulsant agents: what is the evidence from animal experiments? Epilepsia. 2007;48(3):412–434.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Czuczwar SJ. Isobolographic and subthreshold methods in the detection of interactions between oxcarbazepine and conventional antiepileptics–a comparative study. Epilepsy Res. 2003;56(1):27–42.
   PubMed Web of Science ®Google Scholar
• Tallarida RJ. Drug synergism: its detection and applications. J Pharmacol Exp Ther. 2001;298(3):865–872.
   PubMed Web of Science ®Google Scholar
• Berenbaum MC. What is synergy? Pharmacol Rev. Erratum Published in Pharmacol Rev. 1989;41(2):93–141. 1989;41(3): 422.
   PubMed Web of Science ®Google Scholar
• Porreca F, Jiang Q, Tallarida RJ. Modulation of morphine antinociception by peripheral [Leu5]enkephalin: a synergistic interaction. Eur J Pharmacol. 1990;179(3):463–468.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Andres-Mach MM, Ratnaraj N, et al. Levetiracetam and felbamate interact both pharmacodynamically and pharmacokinetically: an isobolographic analysis in the mouse maximal electroshock model. Epilepsia. 2007;48(4):806–815.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Czuczwar SJ. Biphasic characteristic of interactions between stiripentol and carbamazepine in the mouse maximal electroshock-induced seizure model: a three-dimensional isobolographic analysis. Naunyn Schmiedebergs Arch Pharmacol. 2006;374(1):51–64.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Trojnar MK, Ratnaraj N, et al. Interactions of stiripentol with clobazam and valproate in the mouse maximal electroshock-induced seizure model. Epilepsy Res. 2010;90(3):188–198.
   PubMed Web of Science ®Google Scholar
• Baldelli S, Cattaneo D, Giodini L, et al. Development and validation of a HPLC-UV method for the quantification of antiepileptic drugs in dried plasma spots. Clin Chem Lab Med. 2015;53(3):435–444.
   PubMed Web of Science ®Google Scholar
• Naik GS, Kodagali R, Mathew BS, et al. Therapeutic drug monitoring of levetiracetam and lamotrigine: is there a need? Ther Drug Monit. 2015;37(4):437–444.
   PubMed Web of Science ®Google Scholar
• Piskorska B, Miziak B, Czuczwar SJ, et al. Safety issues around misuse of antiepileptics. Expert Opin Drug Saf. 2013;12(5):647–657.
   PubMed Web of Science ®Google Scholar
• Hilgers A, Schaefer M. Systematic adverse drug reaction monitoring of patients under newer antiepileptic drugs using routine clinical data of inpatients. Drugs Real World Outcomes. 2016;3(2):209–221.
   PubMedGoogle Scholar
• Deckers CLP, Genton P, Sills GJ, et al. Current limitations of antiepileptic drug therapy: a conference review. Epilepsy Res. 2003;53(1–2):1–17.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Wu JZ, Raszewski G, et al. Isobolographic characterization of interactions of retigabine with carbamazepine, lamotrigine, and valproate in the mouse maximal electroshock-induced seizure model. Naunyn Schmiedebergs Arch Pharmacol. 2009;379(2):163–179.
   PubMed Web of Science ®Google Scholar
• Chez MG, Bourgeois BFD, Pippenger E, et al. Pharmacodynamic interactions between phenytoin and valproate: individual and combined antiepileptic and neurotoxic action in mice. Clin Neuropharmacol. 1994;17(1):32–37.
   PubMed Web of Science ®Google Scholar
• Bourgeois BFD. Anticonvulsant potency and neurotoxicity of valproate alone and in combination with carbamazepine or phenobarbital. Clin Neuropharmacol. 1988;11(4):348–359.
   PubMed Web of Science ®Google Scholar
• Bourgeois BFD. Antiepileptic drug combinations and experimental background: the case of phenobarbital and phenytoin. Naunyn Schmiedebergs Arch Pharmacol. 1986;333(4):406–411.
   PubMed Web of Science ®Google Scholar
• Gennings C, Sofia RD, Carchman RA, et al. Analysis of anticonvulsant and neurotoxic responses to combination therapy with carbamazepine, felbamate and phenytoin by response-surface modeling. Arzneimittelforschung. 1995;45(7):739–748.
   PubMed Web of Science ®Google Scholar
• Bourgeois BFD. Combination of valproate and ethosuximide: antiepileptic and neurotoxic interaction. J Pharmacol Exp Ther. 1988;247(3):1128–1132.
   PubMed Web of Science ®Google Scholar
• Shank RP, Gardocki JF, Streeter AJ, et al. An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia. 2000;41(Suppl 1):S3–S9.
   PubMed Web of Science ®Google Scholar
• Borowicz KK, Swiader M, Luszczki J, et al. Effect of gabapentin on the anticonvulsant activity of antiepileptic drugs against electroconvulsions in mice: an isobolographic analysis. Epilepsia. 2002;43(9):956–963.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Czuczwar M, Kis J, et al. Interactions of lamotrigine with topiramate and first-generation antiepileptic drugs in the maximal electroshock test in mice: an isobolographic analysis. Epilepsia. 2003;44(8):1003–1013.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Borowicz KK, Swiader M, et al. Interactions between oxcarbazepine and conventional antiepileptic drugs in the maximal electroshock test in mice: an isobolographic analysis. Epilepsia. 2003;44(4):489–499.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Andres MM, Czuczwar P, et al. Pharmacodynamic and pharmacokinetic characterization of interactions between levetiracetam and numerous antiepileptic drugs in the mouse maximal electroshock seizure model: an isobolographic analysis. Epilepsia. 2006;47(1):10–20.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ. Interaction of pregabalin with carbamazepine in the mouse maximal electroshock-induced seizure model: a type I isobolographic analysis for non-parallel dose-response relationship curves. Adv Med Sci. 2010;55(1):43–52.
   PubMed Web of Science ®Google Scholar
• Luszczki J, Swiader M, Czuczwar M, et al. Interactions of tiagabine with some antiepileptics in the maximal electroshock in mice. Pharmacol Biochem Behav. 2003;75(2):319–327.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Ratnaraj N, Patsalos PN, et al. Characterization of the anticonvulsant, behavioral and pharmacokinetic interaction profiles of stiripentol in combination with clonazepam, ethosuximide, phenobarbital, and valproate using isobolographic analysis. Epilepsia. 2006;47(11):1841–1854.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Wojcik-Cwikla J, Andres MM, et al. Pharmacological and behavioral characteristics of interactions between vigabatrin and conventional antiepileptic drugs in pentylenetetrazole-induced seizures in mice: an isobolographic analysis. Neuropsychopharmacology. 2005;30(5):958–973.
   PubMed Web of Science ®Google Scholar
• Dudra-Jastrzebska M, Andres-Mach MM, Ratnaraj N, et al. Isobolographic characterization of the anticonvulsant interaction profiles of levetiracetam in combination with clonazepam, ethosuximide, phenobarbital and valproate in the mouse pentylenetetrazole-induced seizure model. Seizure. 2009;18(9):607–614.
   PubMed Web of Science ®Google Scholar
• Wojda E, Wlaz A, Patsalos PN, et al. Isobolographic characterization of interactions of levetiracetam with the various antiepileptic drugs in the mouse 6 Hz psychomotor seizure model. Epilepsy Res. 2009;86(2–3):163–174.
   PubMed Web of Science ®Google Scholar
• Florek-Luszczki M, Wlaz A, Luszczki JJ. Interactions of levetiracetam with carbamazepine, phenytoin, topiramate and vigabatrin in the mouse 6Hz psychomotor seizure model - a type II isobolographic analysis. Eur J Pharmacol. 2014;723:410–418.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Czuczwar SJ. Preclinical profile of combinations of some second-generation antiepileptic drugs: an isobolographic analysis. Epilepsia. 2004;45(8):895–907.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ. Isobolographic analysis of interaction between drugs with nonparallel dose-response relationship curves: a practical application. Naunyn Schmiedebergs Arch Pharmacol. 2007;375(2):105–114.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Andres MM, Czuczwar SJ. Synergistic interaction of gabapentin and oxcarbazepine in the mouse maximal electroshock seizure model – an isobolographic analysis. Eur J Pharmacol. 2005;515(1–3):54–61.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Filip D, Czuczwar SJ. Additive interactions of pregabalin with lamotrigine, oxcarbazepine and topiramate in the mouse maximal electroshock-induced seizure model: a type I isobolographic analysis for non-parallel dose-response relationship curves. Epilepsy Res. 2010;91(2–3):166–175.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Zagaja M, Miziak B, et al. Beneficial combination of lacosamide with retigabine in experimental animals: an isobolographic analysis. Pharmacology. 2018;101(1–2):22–28.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Zagaja M, Miziak B, et al. Synergistic interaction of retigabine with levetiracetam in the mouse maximal electroshock-induced seizure model: a type ii isobolographic analysis. Pharmacology. 2015;96(1–2):11–15.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Swiader M, Parada-Turska J, et al. Tiagabine synergistically interacts with gabapentin in the electroconvulsive threshold test in mice. Neuropsychopharmacology. 2003;28(10):1817–1830.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Czuczwar SJ. Isobolographic profile of interactions between tiagabine and gabapentin: a preclinical study. Naunyn Schmiedebergs Arch Pharmacol. 2004;369(4):434–446.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Ratnaraj N, Patsalos PN, et al. Isobolographic and behavioral characterizations of interactions between vigabatrin and gabapentin in two experimental models of epilepsy. Eur J Pharmacol. 2008;595(1–3):13–21.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Czuczwar SJ. Isobolographic characterisation of interactions among selected newer antiepileptic drugs in the mouse pentylenetetrazole-induced seizure model. Naunyn Schmiedebergs Arch Pharmacol. 2005;372(1):41–54.
   PubMed Web of Science ®Google Scholar
• Dudra-Jastrzebska M, Andres-Mach MM, Sielski M, et al. Pharmacodynamic and pharmacokinetic interaction profiles of levetiracetam in combination with gabapentin, tiagabine and vigabatrin in the mouse pentylenetetrazole-induced seizure model: an isobolographic analysis. Eur J Pharmacol. 2009;605(1–3):87–94.
   PubMed Web of Science ®Google Scholar
• Shandra A, Shandra P, Kaschenko O, et al. Synergism of lacosamide with established antiepileptic drugs in the 6-Hz seizure model in mice. Epilepsia. 2013;54(7):1167–1175.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ. Isobolographic analysis of interaction for three-drug combination of carbamazepine, phenobarbital and topiramate in the mouse maximal electroshock-induced seizure model. Pharmacology. 2016;97(5–6):259–264.
   PubMed Web of Science ®Google Scholar
• Stephen LJ, Brodie MJ. Seizure freedom with more than one antiepileptic drug. Seizure. 2002;11(6):349–351.
   PubMed Web of Science ®Google Scholar
• Stephen LJ, Forsyth M, Kelly K, et al. Antiepileptic drug combinations–have newer agents altered clinical outcomes? Epilepsy Res. 2012;98(2–3):194–198.
   PubMed Web of Science ®Google Scholar
• Brigo F, Ausserer H, Tezzon F, et al. When one plus one makes three: the quest for rational antiepileptic polytherapy with supraadditive anticonvulsant efficacy. Epilepsy Behav. 2013;27(3):439–442.
   PubMed Web of Science ®Google Scholar
• Brodie MJ, Yuen AW. Lamotrigine substitution study: evidence for synergism with sodium valproate? 105 Study Group. Epilepsy Res. 1997;26(3):423–432.
   PubMed Web of Science ®Google Scholar
• Pisani F, Oteri G, Russo MF, et al. The efficacy of valproate-lamotrigine comedication in refractory complex partial seizures: evidence for a pharmacodynamics interaction. Epilepsia. 1999;40(8):1141–1146.
   PubMed Web of Science ®Google Scholar
• Besag FM, Berry DJ, Pool F, et al. Carbamazepine toxicity with lamotrigine: pharmacokinetic or pharmacodynamic interaction? Epilepsia. 1998;39(2):183–187.
   PubMed Web of Science ®Google Scholar
• De Romanis F, Sopranzi N. Lamotrigine in the therapy of resistant epilepsy. Clin Ter. 1999;150(4):279–282. Italian.
   PubMedGoogle Scholar
• Kaminski RM, Matagne A, Patsalos PN, et al. Benefit of combination therapy in epilepsy: a review of the preclinical evidence with levetiracetam. Epilepsia. 2009;50(3):387–397.
   PubMed Web of Science ®Google Scholar
• Lasoń W, Dudra-Jastrzębska M, Rejdak K, et al. Basic mechanisms of antiepileptic drugs and their pharmacokinetic/pharmacodynamic interactions: an update. Pharmacol Rep. 2011;63(2):271–292.
   PubMed Web of Science ®Google Scholar
• Löscher W. Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs. Seizure. 2011;20(5):359–368.
   PubMed Web of Science ®Google Scholar
• Barton ME, Klein BD, Wolf HH, et al. Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy. Epilepsy Res. 2001;47(3):217–227.
   PubMed Web of Science ®Google Scholar
• Seyfried TN, Todorova MT, Poderycki MJ. Experimental models of multifactorial epilepsies: the EL mouse and mice susceptible to audiogenic seizures. Adv Neurol. 1999;79:279–290.
   PubMedGoogle Scholar
• De Sarro G, Spagnolo C, Gareri P, et al. Gabapentin potentiates the antiseizure activity of certain anticonvulsants in DBA/2 mice. Eur J Pharmacol. 1998;349(2–3):179–185.
   PubMed Web of Science ®Google Scholar
• Schmidt D. Drug treatment strategies for epilepsy revisited: starting early or late? One drug or several drugs? Epileptic Disord. 2016;18(4):356–366.
   PubMed Web of Science ®Google Scholar
• Barker-Haliski M, Sills GJ, White HS. What are the arguments for and against rational therapy for epilepsy? In: scharfman HE, Buckmaster PS, editors. In:: Issues in clinical epileptology: a view from the bench.. Dordrecht: Springer Science. 2014. p. 295–308.
   Google Scholar
• Potschka H. Animal models of drug-resistant epilepsy. Epileptic Disord. 2012;14(3):226–234.
   PubMed Web of Science ®Google Scholar
• Radzik I, Miziak B, Dudka J, et al. Prospects of epileptogenesis prevention. Pharmacol Rep. 2015;67(3):663–668.
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Czuczwar SJ. Three-dimensional isobolographic analysis of interactions between lamotrigine and clonazepam in maximal electroshock-induced seizures in mice. Naunyn Schmiedebergs Arch Pharmacol. 2004;370(5):369–380.
   PubMed Web of Science ®Google Scholar