Antiseizure medications striving for no seizures, no side effects pediatric perspectives

• smooth sailing epilepsy, the 60% rule • rough riding epilepsy • drug resistance, medical intractability • the Brodie study; how do we predict intractability • at least 14 new anti-epilepsy medications • the age of choice: efficacy verses side-effects • majority approved for partial seizures • pediatric challenges • monotherapy the mantra • combining AED’s, rational or obligatory polytherapy • can one and one make three • “the combinations of bromides with other drugs are of much value in the treatment of epilepsy. In many cases a greater effect is produced by the combination than by • age related epilepsy syndrome • neurologically and developmentally normal • absence seizures, pyknolepsy • eeg: normal BG, hyperventilation activated H • universal tendency to remission • which medications • double blind, randomized, controlled trial • primary outcome: freedom from treatment • freedom from treatment failure – combination of • persistence of absence seizures week 16 or • generalized tonic clonic seizure at any time • platelet count <50,000 per mm3 • moderately severe rash • Increase in BMI • free of treatment failure: 209/446 (47%) • lack of seizure control: 109/446 (24%) • intolerable side effects: 97/446 (22%) • lack of seizure control – ethosuximide: 22/154 (14%) – lamotrigine: 69/146 (47%) – valproic acid: 18/146 (12%) • secondary outcome: continuous performance testing – ethosuximide: 35/106 (33%) – lamotrigine: 25/104 (24%) – valproic acid: 52/106 (48%) • no differences in the confidence index results between seizure free subjects and those who continued to have seizures • attentional difficulties not simply a result of the seizures, • childhood epileptic encephalopathy with slow • 1 to 8 years; cryptogenic or symptomatic • drops, nods, blinks, jerks • slow BG; slow (1 ½ to 2 ½ Hz) spike and wave • generalized paroxysmal fast activity • typically medically intransigent • at the onset of seizures, only 30% to 50% have intellectual delay, but after 4 years 78% to 96% will be affected • no comparative drug studies • six medications approved by the FDA • lamotrigine, topiramare, felbamate, rufinamide, • majority of practitioners still use valproate as • role of “partial” medications: dilantin, lacosamide, oxcarbazepine (multiple independent spike foci) • >50% median seizure reduction rates and • Lamotrigine: 33%: 9% rash (7% placebo) • Topamax: 33%: somnolence, behavioral • Rufinamide: 31%, somnolence, vomiting • Clobazam – high dose: 77%, somnolence, drooling – moderate dose: 58% – low dose: 43% • >50% median seizure reduction rates • VNS: 21% - 83% • corpus callosotomy: >80% reduction in – >23%, a 90% reduction in seizures – waning effectiveness after 12 months • severe myoclonic epilepsy of infancy • 1 in 40,000; M:F = 2:1 • prolonged febrile seizures followed by Todd’s • myoclonic, atypical absence, and partial • cognitive impairment; visual attention, visual motor integration, visual perception and executive function • SCN1a mutation; affects sodium currents in • Topiramate: 3 of 5 had >50% reductions in • Levetiracetam: 18/28 a positive response – 3/28 with tonic clonic seizures, 2/28 with myoclonic seizures, 3/28 with focal seizures and 1/28 with absence seizures became seizure free • Stiripentol: 8/37 in one study seizure free – 15/21 in another study had 50% drop in • combination of valproic acid, clobazam • levetiracetam also a good option • topiramate, mixed results • broad spectrum medications • consider the seizure type • absence, ethosuximide, lamictal, zonisamide, • myoclonic; levetiracetam, lamotrigine, • tonic; lamictal, zonisamide, rufinamide, • the balance between seizure control and • what is optimal seizure control • what are acceptable side effects • rational, methodical trials of effective anti- • obligatory polytherapy • the cross-over trap • early consideration of non-pharmacologic • maximise neurodevelopmental outcomes

Source: http://www.epilepsymichigan.org/ckfinder/userfiles/files/Constantinou%20Pediatric%20Meds%202013.pdf