Innovations in Epilepsy Management – An Overview

Abraham, Suja; Shaju, Minumaria

doi:10.18433/j32k5b

Cited by 18 publications

(8 citation statements)

References 78 publications

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“…Taken together, these results raise public concerns on the bone growth or other medical conditions of children with epilepsy taking AEDs. So far, several newer-generation AEDs, including fosphenytoin, zonisamide, lacosamide, perampanel, eslicarbazepine, felbamate, ezogabine/retigabine, stiripentol, tiagabine, and rufinamide, have been designed and marketed [204]. Most of them have broader spectrums, fewer drug interactions, better tolerance, and minimal side effects, including bone diseases [205].…”

Section: Discussionmentioning

confidence: 99%

The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism

Fan

Lee

Chang

et al. 2016

IJMS

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Epilepsy is a common neurological disorder worldwide and anti-epileptic drugs (AEDs) are always the first choice for treatment. However, more than 50% of patients with epilepsy who take AEDs have reported bone abnormalities. Cytochrome P450 (CYP450) isoenzymes are induced by AEDs, especially the classical AEDs, such as benzodiazepines (BZDs), carbamazepine (CBZ), phenytoin (PT), phenobarbital (PB), and valproic acid (VPA). The induction of CYP450 isoenzymes may cause vitamin D deficiency, hypocalcemia, increased fracture risks, and altered bone turnover, leading to impaired bone mineral density (BMD). Newer AEDs, such as levetiracetam (LEV), oxcarbazepine (OXC), lamotrigine (LTG), topiramate (TPM), gabapentin (GP), and vigabatrin (VB) have broader spectra, and are safer and better tolerated than the classical AEDs. The effects of AEDs on bone health are controversial. This review focuses on the impact of AEDs on growth and bone metabolism and emphasizes the need for caution and timely withdrawal of these medications to avoid serious disabilities.

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Section: Discussionmentioning

confidence: 99%

The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism

Fan

Lee

Chang

et al. 2016

IJMS

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“…There are several anticonvulsants besides ganaxolone which are currently in the stage of clinical development: brivaracetam, seletracetam, talampanel, fluorofelbamate, carisbamate, and losigamone 14 . Being analogues of levetiracetam, brivaracetam and seletracetam bind with high-affinity for synaptic vesicle protein 2A (SV2A) and brivaracetam also inhibits voltage-gated sodium channels; talampanel is non-competitive allosteric blocker of alpha-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and weak inhibitor of kainite receptors for glutamate 15 .…”

Section: New Anticonvulsantsmentioning

confidence: 99%

Antiepileptic potential of ganaxolone

Janković

Lukić

2017

VSP

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Drug name (generic) and route of administration: ganaxolone, oral. Clinical trial phase (for indication under discussion): phase III. Pharmacology description/mechanism of action: Ganaxolone binds for unique recognition site on the GABA-A receptor which is different from the binding sites of GABA, benzodiazepines and barbiturates. After binding, ganaxolone potentiates inhibitory action of GABA on neurons which carry the GABA-A receptor. Indication: drug-resistant, partial onset seizures in adult patients, with or without secondary generalization. Chemical structure: 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one. Key trial(s): Phase I: 7 phase I studies conducted on 87 healthy adult male and 9 healthy adult female volunteers 59 ; Phase II: Assessment of ganaxolone's anticonvulsant activity against complex partial seizures in adults with epilepsy using a randomized, double-blind, presurgical trial design, and another double-blind, placebo controlled and randomized study conducted with 147 patients suffering from partial onset seizures with or without secondary generalization and refractory to previously used anti-convulsants 61. Phase III: An ongoing multicenter, randomized, double-blind and placebo-controlled study investigating efficacy and safety of ganaxolone as add-on antiepileptic therapy for adult patients with partial-onset seizures that were not controlled with previous therapy 66 .

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“…This anachronistic issue concerns any longitudinal study with follow-up of a cohort for many decades. It is to be noted, however, that there is so far no objective evidence of the superiority of the new AEDs to older ones in terms of therapeutic efficacy (Perucca, 2002;Snead and Donner, 2007;Gauffin et al, 2009;Schmidt, 2011;Abraham and Shaju, 2013;Löscher et al, 2013).…”

Section: Cure Of Epilepsy (Sillanpää Et Al 2014)mentioning

confidence: 99%

Natural course of treated epilepsy and medico-social outcomes. Turku studies. Part II

Sillanpää¹

2016

Journal of Epileptology

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SummaryIntroduction. Population-based data on the prognosis of childhood-onset epilepsy were almost nonexistent in the 1960s. This prompted me to start an epidemiological prospective study on children with epilepsy.Aim. To study the medical and social outcome of children with epilepsy.Methods. The most important personal data on the natural course and outcome were reviewed and compared with the relevant data of other investigators.Results and discussion. The natural course of treated epilepsy is remitting, uninterrupted by relapse (in 48%); a remitting-relapsing course (interrupted by relapses, in terminal remission) (19%); worsening course (early or late remission followed by drug-resistant epilepsy) (14%); and never in ≥5-year remission (drug resistance) (19%) The medical and social outcomes based on my unique, five decades followed cohort show that most subjects are in 10-year remission without medications, which is the definition of resolved epilepsy. Normal or subnormal IQ, non-symptomatic etiology, and low seizure frequency both in the first year of AED treatment and prior to medication appear to be clinical predictors of cure in childhood-onset epilepsy. Subjects with 1-year remission during the first five years form onset of treatment have more than 10-fold chance for entering 5-year terminal remission vs those who have no 1-year remission during the first five years. Even about one fourth of difficult-to-treat subjects become seizure free on medication and more than half of them enter one or more 5-year remissions. Epilepsy has a substantial impact on quality of life even in those who are seizure free off medication for many years and particularly those not in remission or in remission but still on medication.Conclusions. The prognosis is excellent for medical and social outcome. The successful outcome is confirmed by several longitudinal studies from recent decades. Good response to early drug therapy does not necessarily guarantee a favorable seizure outcome, and even a late good response may still predict a successful prognosis. Our life-cycle study is being continued and targets to answer the question whether or not childhood-onset epilepsy is a risk factor for premature and/or increased incidence of mental impairment and dementia.

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Innovations in Epilepsy Management – An Overview

Cited by 18 publications

References 78 publications

The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism

The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism

Antiepileptic potential of ganaxolone

Natural course of treated epilepsy and medico-social outcomes. Turku studies. Part II

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