A 2017 review of pharmacotherapy for treating focal epilepsy: where are we now and how will treatment develop?

References

• WHO. [ cited 2017 Jul]. Available from: http://www.who.int/mediacentre/factsheets/fs999/en/
   Google Scholar
• Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55:475–482.
   PubMed Web of Science ®Google Scholar
• Rheims S, Ryvlin P. Retigabine for partial onset seizures. Expert Rev Neurother. 2012;12:509–517.
   PubMed Web of Science ®Google Scholar
• Schulze-Bonhage A. Perampanel for epilepsy with partial-onset seizures: a pharmacokinetic and pharmacodynamic evaluation. Expert Opin Drug Metab Toxicol. 2015;11:1329–1337.
   PubMed Web of Science ®Google Scholar
• Zaccara G. Brivaracetam: new compound approved for the treatment of epilepsy. Drugs Today (Barc). 2016;52:219–227.
   PubMed Web of Science ®Google Scholar
• Yates SL, Fakhoury T, Liang W, et al. An open-label, prospective, exploratory study of patients with epilepsy switching from levetiracetam to brivaracetam. Epilepsy Behav. 2015;52:165–168.
   PubMed Web of Science ®Google Scholar
• Patsalos PN. Drug interactions with the newer antiepileptic drugs (AEDs)-part 1: pharmacokinetic and pharmacodynamic interactions between AEDs. Clin Pharmacokinet. 2013;52:927–966.
   PubMed Web of Science ®Google Scholar
• Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369:1000–1015.
   PubMed Web of Science ®Google Scholar
• Ferrie CD, Grünewald RA, Livingston JH, et al. Treatment of newly diagnosed epilepsies: the shortcomings of SANAD. Dev Med Child Neurol. 2008;50:247.
   PubMed Web of Science ®Google Scholar
• Campos MS, Ayres LR, Morelo MR, et al. Efficacy and tolerability of antiepileptic drugs in patients with focal epilepsy: systematic review and network meta-analyses Pharmacotherapy. 2016;36:1255–1271.
   Google Scholar
• Stephen LJ, Forsyth M, Kelly K, et al. Antiepileptic drug combinations-have newer agents altered clinical outcomes? Epilepsy Res. 2012;98:194–198.
   PubMed Web of Science ®Google Scholar
• Beyenburg S, Stavem K, Schmidt D. Placebo-corrected efficacy of modern nonenzyme-inducing AEDs for refractory focal epilepsy: systematic review and meta-analysis. Epilepsia. 2012;53:512–520.
   PubMed Web of Science ®Google Scholar
• Walker MC, Sander JW. The impact of new antiepileptic drugs on the prognosis of epilepsy: seizure freedom should be the ultimate goal. Neurology. 1996;46:912–914.
   PubMed Web of Science ®Google Scholar
• Jacoby A, Snape D, Baker GA. Determinants of quality of life in people with epilepsy. Neurol Clin. 2009;27:843–863.
   PubMed Web of Science ®Google Scholar
• Granbichler CA, Oberaigner W, Kuchukhidze G, et al. Decrease in mortality of adult epilepsy patients since 1980: lessons learned from a hospital-based cohort. Eur J Neurol. 2017;24:667–672.
   PubMed Web of Science ®Google Scholar
• Striano P, Belcastro V, Coppola A, et al. Antiepileptic drugs under investigation for treatment of focal epilepsy. Clin Neuropharmacol. 2016;39:281–287.
   PubMed Web of Science ®Google Scholar
• Bialer M, Johannessen SI, Levy RH, et al. Progress report on new antiepileptic drugs: a summary of the Twelfth Eilat Conference (EILAT XII). Epilepsy Res. 2015;111:85–141.
   PubMed Web of Science ®Google Scholar
• Bialer M, Johannessen SI, Levy RH, et al. Progress report on new antiepileptic drugs: a summary of the Thirteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIII). Epilepsia. 2017;58:181–221.
   PubMed Web of Science ®Google Scholar
• Wasterlain CG, Liu H, Naylor DE, et al. Molecular basis of self-sustaining seizures and pharmacoresistance during status epilepticus: the receptor trafficking hypothesis revisited. Epilepsia. 2009;50(S 12):16–18.
   PubMedGoogle Scholar
• Devinsky O, Cross JH, Laux L, et al. Cannabidiol in Dravet Syndrome Study Group. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017;376:2011–2020.
   PubMed Web of Science ®Google Scholar
• Schoonjans A, Paelinck BP, Marchau F, et al. Low-dose fenfluramine significantly reduces seizure frequency in Dravet syndrome: a prospective study of a new cohort of patients. Eur J Neurol. 2017;24:309–314.
   PubMed Web of Science ®Google Scholar
• Broomall E, Natale JE, Grimason M, et al. Pediatric super-refractory status epilepticus treated with allopregnanolone. Ann Neurol. 2014;76:911–915.
   PubMed Web of Science ®Google Scholar
• Schulze-Bonhage A. Epileptogenesis. In: Shorvon S, editor. The causes of epilepsy. Cambridge, UK: Cambridge University Press; 2017. in press
   Google Scholar
• Bialer M, White HS. Key factors in the discovery and development of new antiepileptic drugs. Nat Rev Drug Discov. 2010;9:68–82.
   PubMed Web of Science ®Google Scholar
• Löscher W, Schmidt D. Modern antiepileptic drug development has failed to deliver: ways out of the current dilemma. Epilepsia. 2011;52:657–678.
   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;20:359–368.
   PubMed Web of Science ®Google Scholar
• Simonato M, Löscher W, Cole AJ, et al. Finding a better drug for epilepsy: preclinical screening strategies and experimental trial design. Epilepsia. 2012;53:1860–1867.
   PubMed Web of Science ®Google Scholar
• Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Eng J Med. 2000;342:314–319.
   PubMed Web of Science ®Google Scholar
• Schiller Y, Najjar Y. Quantifying the response to antiepileptic drugs: effect of past treatment history. Neurology. 2008;70:54–56.
   PubMed Web of Science ®Google Scholar
• Rheims S, Perucca E, Cucherat M, et al. Factors determining response to antiepileptic drugs in randomized controlled trials. A systematic review and meta-analysis. Epilepsia. 2011;52:219–233.
   PubMed Web of Science ®Google Scholar
• Callaghan BC, Anand K, Hesdorffer D, et al. Likelihood of seizure remission in an adult population with refractory epilepsy. Ann Neurol. 2007;62:382–389.
   PubMed Web of Science ®Google Scholar
• Luciano AL, Shorvon S. Results of treatment changes in patients with apparently drug-resistant chronic epilepsy. Ann Neurol. 2007;62:375–381.
   PubMed Web of Science ®Google Scholar
• Semah F, Picot MC, Adam C, et al. Is the underlying cause of epilepsy a major prognostic factor for recurrence? Neurology. 1998;51:1256–1262.
   PubMed Web of Science ®Google Scholar
• Smyth MD, Barbaro NM, Baraban SC. Effects of antiepileptic drugs on induced epileptiform activity in a rat model of dysplasia. Epilepsy Res. 2002;50:251–264.
   PubMed Web of Science ®Google Scholar
• Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51:1069–1077.
   PubMed Web of Science ®Google Scholar
• Engel Jr J, McDermott MP, Wiebe S, et al. Early Randomized Surgical Epilepsy Trial (ERSET) study group. Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial. JAMA. 2012;307:922–930.
   PubMed Web of Science ®Google Scholar
• Schulze-Bonhage A. Brain stimulation as a neuromodulatory treatment of epilepsy. Seizure. 2017;44:169–175.
   PubMed Web of Science ®Google Scholar
• Rogawski MA, Targets M. Versus models for new antiepileptic drug discovery. Epilepsy Res. 2006;68:22–28.
   PubMed Web of Science ®Google Scholar
• Temkin NR. Preventing and treating posttraumatic seizures: the human experience. Epilepsia. 2009;50(Suppl 2):10–13.
   PubMed Web of Science ®Google Scholar
• Beghi E. AED discontinuation may not be dangerous in seizure-free patients. J Neural Transm. (Vienna). 2011;118:187–191.
   PubMed Web of Science ®Google Scholar
• Sillanpää M, Anttinen A, Rinne JO, et al. Childhood-onset epilepsy five decades later. A Prospective Population-Based Cohort Study. Epilepsia. 2015;56:1774–1783.
   Google Scholar
• Berdichevsky Y, Saponjian Y, Mail M, et al. Organotypic culture model of post-traumatic epileptogenesis used as a medium-throughput screen of antiepileptic drugs. Am Epilepsy Soc Annu Meet. 2011;3:026.
   Google Scholar
• Fauser S, Huppertz HJ, Bast T, et al. Clinical characteristics in focal cortical dysplasia: a retrospective evaluation in a series of 120 patients. Brain. 2006;129:1907–1916.
   PubMed Web of Science ®Google Scholar
• Manent JB, Wang Y, Chang Y, et al. DCX reexpression reduces subcortical band heterotopia and seizure threshold in an animal model of neuronal migration disorder. Nature Med. 2009;15:84–90.
   PubMed Web of Science ®Google Scholar
• Vezzani A, Fujinami RS, White HS, et al. Infections, inflammation and epilepsy. Acta Neuropathol. 2016;131:211–234.
   PubMed Web of Science ®Google Scholar
• Ravizza T, Lucas SM, Balosso S, et al. Inactivation of caspase-1 in rodent brain: a novel anticonvulsive strategy. Epilepsia. 2006;47:1160–1168.
   PubMed Web of Science ®Google Scholar
• Dey A, Kang X, Qiu J, et al. Anti-inflammatory small molecules to treat seizures and epilepsy: from bench to bedside. Trends Pharmacol Sci. 2016;37:463–484.
   PubMed Web of Science ®Google Scholar
• Terrone G, Pauletti A, Pascente R, et al. Preventing epileptogenesis: a realistic goal? Pharmacol Res. 2016;110:96–100.
   PubMed Web of Science ®Google Scholar
• Abraham J, Fox PD, Condello C, et al. Minocycline attenuates microglia activation and blocks the long-term epileptogenic effects of early-life seizures. Neurobiol Dis. 2012;46:425–430.
158.
   PubMed Web of Science ®Google Scholar
• Wang N, Mi X, Gao B, et al. Minocycline inhibits brain inflammation and attenuates spontaneous recurrent seizures following pilocarpine-induced status epilepticus. Neuroscience. 2015;287:144–156.
   PubMed Web of Science ®Google Scholar
• Overwater IE, Rietman AB, Bindels-De Heus K, et al. Sirolimus for epilepsy in children with tuberous sclerosis complex: a randomized controlled trial. Neurology. 2016;87:1011–1018.
   PubMedGoogle Scholar
• Schmidt D, Sillanpää M. Prevention of epilepsy: issues and innovations. Curr Neurol Neurosci Rep. 2016;16:95.
   PubMed Web of Science ®Google Scholar
• Bragin A, Wilson CL, Almajano J, et al. High-frequency oscillations after status epilepticus: epileptogenesis and seizure genesis. Epilepsia. 2004;45:1017–1023.
   PubMed Web of Science ®Google Scholar
• Meisel C, Schulze-Bonhage A, Freestone D, et al. Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle. P Natl Acad Sci. 2015;112:14694–14699.
   PubMed Web of Science ®Google Scholar
• Meisel C, Plenz D, Schulze-Bonhage A, et al. Quantifying antiepileptic drug effects using intrinsic excitability measures. Epilepsia. 2016;57:e210–e215.
   PubMed Web of Science ®Google Scholar
• Pitkänen A, Lukasiuk K. Molecular biomarkers of epileptogenesis. Biomark Med. 2011;5:629–633.
   PubMed Web of Science ®Google Scholar
• Löscher W, Klitgaard H, Twyman RE, et al. New avenues for anti-epileptic drug discovery and development. Nat Rev Drug Discov. 2013;12:757–776.
   PubMed Web of Science ®Google Scholar
• Anderson GD. Pharmacokinetic, pharmacodynamic, and pharmacogenetic targeted therapy of antiepileptic drugs. Ther Drug Monit. 2008;30:173–180.
   PubMed Web of Science ®Google Scholar
• Balestrini S, Sisodiya SM. Pharmacogenomics in epilepsy. Neurosci Lett. 2017 Jan 10:394. [Epub ahead of print]. DOI:10.1016/j.neulet.2017.01.014.
   Google Scholar
• McCormack M, Alfirevic A, Bourgeois S, et al. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med. 2011;364:1134–1143.
   PubMed Web of Science ®Google Scholar
• Sake JK, Hebert D, Isojärvi J, et al. A pooled analysis of lacosamide clinical trial data grouped by mechanism of action of concomitant antiepileptic drugs. CNS Drugs. 2010;12:1055–1068.
   Google Scholar
• Ryvlin P, Cucherat M, Rheims S. Risk of sudden unexpected death in epilepsy in patients given adjunctive antiepileptic treatment for refractory seizures: a meta-analysis of placebo-controlled randomised trials. Lancet Neurol. 2011;10:961–968.
   PubMed Web of Science ®Google Scholar