Failure of a first regimen of monotherapy to control the newly diagnosed epilepsies. What to do next?
Background. Monotherapy is the choice regimen to treat newly diagnosed epilepsies. However, if it fails, several strategies may be followed. Aim. To discuss the treatment options when an initial monotherapy regimen fails. Methods. We reviewed the relevant literature on the topic by using PubMed. Review and Discussion. Approximately 64% of people with epilepsy (PWE) de novo are free of seizures with the first appropriate antiepileptic drug (AED) in monotherapy. The type (first versus second generation) of the first AED to use depends on the physician's personal choice provided that it is a first-line AED. There is a tendency to prefer a substitution rather than a combination of a failed first AED when it was produced associated with an idiosyncratic reaction, was poorly tolerated at a moderate dose, or produced no improvement in seizure control. In contrast, there is some evidence to prefer secondary polytherapy whenever the PWE tolerate its first AED but with a suboptimal response. In this case, and particularly mainly if a first generation AED was used as a first-line treatment, I prefer to choose a new generation AED given their more favourable pharmacokinetic and pharmacodynamic profiles. A very often used strategy is transitional polytherapy between two regimens of monotherapy. Conclusion. Any therapeutic decision should take into account factors such as seizure type or syndrome, possibility of drug side effects, comorbidities, comedications, age, teratogenic potential, and compliance. Whatever the option to be taken, the PWE, his family or the caregivers should take part in the decision making.
- Andrew T., Milinis K., Baker G., Galimberti C.A.:Self reported adverse effects of mono and polytherapy for epilepsy. Seizure, 2012, 21: 610–613.[WoS][PubMed][Crossref]
- Brodie M.J., Barry S.J.E., Bamagous G.A., Norrie J.D., Kwan P.:Patterns of treatment response in newly diagnosed epilepsy. Neurology, 2012, 78: 1548–1554.[Crossref][PubMed][WoS]
- Canevini M.P., De Sarro G., Galimberti C.A., Gatti G., Licchetta L., Malerba A. et al.:on behalf of the SOPHIE Study Group.: Relationship between adverse effects of antiepileptics drugs, number of coprescribed drugs, and drug load in a large cohort of consecutive patients with drug-refractory epilepsy. Epilepsia, 2010, 51: 797–804.[Crossref][WoS]
- Deckers C.L.P.:Place of politherapy in the early treatment of epilepsy. CNS Drugs, 2002, 16: 155–163.[Crossref]
- Deckers C.L.P., Hekster Y.A., Keyser A., Meinardi H., Renier W.O.:Monotherapy versus polytherapy for epilepsy: a multicenter double-blind randomized study. Epilepsia, 2001, 42: 1387–1394.[PubMed]
- Garnett W.R., St. Louis E.K., Henry T.R., Bramley T.:Transitional polytherapy: tricks of the trade for monotherapy to monotherapy AED conversation. Cur. Neuropharmacol., 2009, 7: 83–95.
- Glauser T., Ben-Menachem E., Bourgeois B., Cnaan A., Guerreiro C., Kälviäinen R., Mattson R., French J.A., Perucca E., Tomsom T. for the ILAE Subcommission on AED Guidelines.:Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia, 2013, 54: 551–563.[WoS][Crossref]
- Kwan P., Brodie M.J.:Early identification of refractory epilepsy. N. Engl. J. Med., 2000a, 342: 314–319.
- Kwan P., Brodie M.J.:Epilepsy after the first drug fails: substitution or add-on? Seizure, 2000b, 9: 464–468.[PubMed][Crossref]
- Kwan P., Brodie M.J.:Combination therapy in epilepsy: when and what to use. Drugs, 2006, 66: 1817–1829.[Crossref][PubMed]
- Marson A.G., Al-Kharusi A.M., Alwaidh M., Appleton R., Baker G.A., Chadwick D.W. et al., on behalf of the SANAD Study group:The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet, 2007a, 369: 1016–1026.[WoS]
- Marson A.G., Al-Kharusi A.M., Alwaidh M., Appleton R., Baker G.A., Chadwick D.W. et al., on behalf of the SANAD Study group:The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet, 2007b, 369: 1000–1015.[WoS]
- Mattson R.H., Cramer J.A., Collins J.F.:Comparision of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. N. Engl. J. Med., 1985, 313: 145–151.[Crossref]
- Millul A., Iudice A., Adami M., Porzio R., Mattana F., Beghi E.: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: 494–500.[WoS][PubMed][Crossref]
- National Institute for Health and Clinical Excellence:The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care. 2012 ()
- Perucca E., Tomson T.:The pharmacological treatment of epilepsy in adults. Lancet Neurol., 2011, 10: 446–456.[WoS][PubMed][Crossref]
- Schmidt D.:Reduction of two-drug therapy in intractable epilepsy. Epilepsia, 1983, 24: 368–376.[Crossref][PubMed]
- Shorvon S.D., Chadwick D., Galbraith A.W., Reynolds E.H.:One drug for epilepsy. Br. Med. J., 1978, 342: 314–319.
- Stephen L.J., Brodie M.J.:Antiepileptic drug monotherapy versus polytherapy: pursuing seizure freedom and tolerability in adults. Curr. Opin. Neurol., 2012, 25:164–172.[WoS][PubMed][Crossref]
- Smith B.J., St. Louis E.K., Stern J.M., Green C., Bramley T.:Concerns with AED conversation: comparison of patient and physician perspectives. Curr. Neuropharmacol., 2009, 7: 120–124.[WoS][Crossref]