scholarly journals Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy

Neurology ◽  
2018 ◽  
Vol 91 (2) ◽  
pp. 82-90 ◽  
Author(s):  
Andres M. Kanner ◽  
Eric Ashman ◽  
David Gloss ◽  
Cynthia Harden ◽  
Blaise Bourgeois ◽  
...  
Keyword(s):  
Antiepileptic Drugs ◽  
Seizure Frequency ◽  
Extended Release ◽  
Focal Epilepsy ◽  
Immediate Release ◽  
Juvenile Myoclonic Epilepsy ◽  
Review Literature ◽  
Treatment Resistant ◽  
New Antiepileptic Drugs ◽  
Frequency Level

ObjectiveTo update the 2004 American Academy of Neurology guideline for managing treatment-resistant (TR) epilepsy with second- and third-generation antiepileptic drugs (AEDs).Methods2004 criteria were used to systemically review literature (January 2003 to November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength.ResultsForty-two articles were included.RecommendationsThe following are established as effective to reduce seizure frequency (Level A): immediate-release pregabalin and perampanel for TR adult focal epilepsy (TRAFE); vigabatrin for TRAFE (not first-line treatment); rufinamide for Lennox-Gastaut syndrome (LGS) (add-on therapy). The following should be considered to decrease seizure frequency (Level B): lacosamide, eslicarbazepine, and extended-release topiramate for TRAFE (ezogabine production discontinued); immediate- and extended-release lamotrigine for generalized epilepsy with TR generalized tonic-clonic (GTC) seizures in adults; levetiracetam (add-on therapy) for TR childhood focal epilepsy (TRCFE) (1 month–16 years), TR GTC seizures, and TR juvenile myoclonic epilepsy; clobazam for LGS (add-on therapy); zonisamide for TRCFE (6–17 years); oxcarbazepine for TRCFE (1 month–4 years). The text presents Level C recommendations. AED selection depends on seizure/syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. This evidence-based assessment informs AED prescription guidelines for TR epilepsy and indicates seizure types and syndromes needing more evidence. A recent Food and Drug Administration (FDA) strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years of age and perampanel as monotherapy received FDA approval.

scholarly journals Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy

2018 ◽  
Vol 18 (4) ◽  
pp. 269-278 ◽  
Author(s):  
Andres M. Kanner ◽  
Eric Ashman ◽  
David Gloss ◽  
Cynthia Harden ◽  
Blaise Bourgeois ◽  
...  
Keyword(s):  
Antiepileptic Drugs ◽  
Seizure Frequency ◽  
Extended Release ◽  
Focal Epilepsy ◽  
Immediate Release ◽  
Juvenile Myoclonic Epilepsy ◽  
Review Literature ◽  
Treatment Resistant ◽  
New Antiepileptic Drugs ◽  
Frequency Level

Objective: To update the 2004 American Academy of Neurology (AAN) guideline for managing treatment-resistant (TR) epilepsy with second- and third-generation antiepileptic drugs (AEDs). Methods: 2004 criteria were used to systematically review literature (January 2003 to November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. Results: Forty-two articles were included. Recommendations: The following are established as effective to reduce seizure frequency (Level A): immediate-release pregabalin and perampanel for TR adult focal epilepsy (TRAFE); vigabatrin for TRAFE (not first-line treatment; rufinamide for Lennox–Gastuat syndrome (LGS) (add-on therapy). The following should be considered to decrease seizure frequency (Level B): lacosamide, eslicarbazepine, and extended-release topiramate for TRAFE (ezogabine production discontinued); immediate- and extended-release lamotrigine for generalized epilepsy with TR generalized tonic–clonic (GTC) seizures in adults; levetiracetam (add-on therapy) for TR childhood focal epilepsy (TRCFE) (1 month to 16 years), TR GTC seizures, and TR juvenile myoclonic epilepsy; clobazam for LGS (add-on therapy); zonisamide for TRCFE (6–17 years); oxcarbazepine for TRCFE (1 month to 4 years). The text presents Level C recommendations. AED selection depends on seizure/syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. This evidence-based assessment informs AED prescription guidelines for TR epilepsy and indicates seizure types and syndromes needing more evidence. A recent FDA strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years of age and perampanel as monotherapy received FDA approval.

scholarly journals Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy

Neurology ◽  
2018 ◽  
Vol 91 (2) ◽  
pp. 74-81 ◽  
Author(s):  
Andres M. Kanner ◽  
Eric Ashman ◽  
David Gloss ◽  
Cynthia Harden ◽  
Blaise Bourgeois ◽  
...  
Keyword(s):  
Antiepileptic Drugs ◽  
Seizure Frequency ◽  
Focal Epilepsy ◽  
Juvenile Myoclonic Epilepsy ◽  
Absence Epilepsy ◽  
Review Literature ◽  
Third Generation ◽  
High Quality ◽  
New Antiepileptic Drugs ◽  
New Onset

ObjectiveTo update the 2004 American Academy of Neurology (AAN) guideline for treating new-onset focal or generalized epilepsy with second- and third-generation antiepileptic drugs (AEDs).MethodsThe 2004 AAN criteria were used to systematically review literature (January 2003–November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength.ResultsSeveral second-generation AEDs are effective for new-onset focal epilepsy. Data are lacking on efficacy in new-onset generalized tonic-clonic seizures, juvenile myoclonic epilepsy, or juvenile absence epilepsy, and on efficacy of third-generation AEDs in new-onset epilepsy.RecommendationsLamotrigine (LTG) should (Level B) and levetiracetam (LEV) and zonisamide (ZNS) may (Level C) be considered in decreasing seizure frequency in adults with new-onset focal epilepsy. LTG should (Level B) and gabapentin (GBP) may (Level C) be considered in decreasing seizure frequency in patients ≥60 years of age with new-onset focal epilepsy. Unless there are compelling adverse effect–related concerns, ethosuximide or valproic acid should be considered before LTG to decrease seizure frequency in treating absence seizures in childhood absence epilepsy (level B). No high-quality studies suggest clobazam, eslicarbazepine, ezogabine, felbamate, GBP, lacosamide, LEV, LTG, oxcarbazepine, perampanel, pregabalin, rufinamide, tiagabine, topiramate, vigabatrin, or ZNS is effective in treating new-onset epilepsy because no high-quality studies exist in adults of various ages. A recent Food and Drug Administration (FDA) strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years old and perampanel as monotherapy received FDA approval.

scholarly journals Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy

2018 ◽  
Vol 18 (4) ◽  
pp. 260-268 ◽  
Author(s):  
Andres M. Kanner ◽  
Eric Ashman ◽  
David Gloss ◽  
Cynthia Harden ◽  
Blaise Bourgeois ◽  
...  
Keyword(s):  
Antiepileptic Drugs ◽  
Seizure Frequency ◽  
Focal Epilepsy ◽  
Juvenile Myoclonic Epilepsy ◽  
Absence Epilepsy ◽  
Review Literature ◽  
Third Generation ◽  
High Quality ◽  
New Antiepileptic Drugs ◽  
New Onset

Objective: To update the 2004 American Academy of Neurology (AAN) guideline for treating new-onset focal or generalized epilepsy (GE) with second- and third-generation antiepileptic drugs (AEDs). Methods: The 2004 AAN criteria was used to systematically review literature (January 2003 to November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. Results: Several second-generation AEDs are effective for new-onset focal epilepsy. Data are lacking on efficacy in new-onset generalized tonic–clonic seizures, juvenile myoclonic epilepsy, or juvenile absence epilepsy, and on efficacy of third-generation AEDs in new-onset epilepsy. Recommendations: Lamotrigine (LTG) should (Level B) and levetiracetam (LEV) and zonisamide (ZNS) may (Level C) be considered in decreasing seizure frequency in adults with new-onset focal epilepsy. LTG should (Level B) and gabapentin (GBP) may (Level C) be considered in decreasing seizure frequency in patients ≥60 years with new-onset focal epilepsy. Unless there are compelling adverse-effect–related concerns, ethosuximide (ETS) or valproic acid (VPA) should be considered before LTG to decrease seizure frequency in treating absence seizures in childhood absence epilepsy (Level B). No high-quality studies suggest clobazam, eslicarbazepine, ezogabine, felbamate, GBP, lacosamide, LEV, LTG, oxcarbazepine, perampanel, pregabalin, rufinamide, tiagabine, topiramate, vigabatrin, or ZNS is effective in treating new-onset epilepsy because no high-quality studies exist in adults of various ages. A recent FDA strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years old and perampanel as monotherapy received FDA approval.

scholarly journals Seizure Exacerbation by Antiepileptic Drugs

2005 ◽  
Vol 5 (5) ◽  
pp. 192-193 ◽  
Author(s):  
Jacqueline A. French
Keyword(s):  
Antiepileptic Drugs ◽  
De Novo ◽  
Focal Epilepsy ◽  
Juvenile Myoclonic Epilepsy ◽  
Absence Epilepsy ◽  
Absence Seizures ◽  
Incorrect Diagnosis ◽  
Juvenile Absence Epilepsy ◽  
Generalized Epilepsy

Worsening of Seizures by Oxcarbazepine in Juvenile Idiopathic Generalized Epilepsies Gelisse P, Genton P, Kuate C, Pesenti A, Baldy-Moulinier M, Crespel A Epilepsia 2004;45:1282–1286 Purpose Several studies have shown that carbamazepine (CBZ) may aggravate idiopathic generalized epilepsy (IGE). Oxcarbazepine (OXC) is a new drug chemically related to CBZ. We report six cases of juvenile IGE with a clear aggravation by OXC. Methods We retrospectively studied all patients with IGE first referred to our epilepsy department between January 2001 and June 2003 and treated with OXC. Results During this period, six patients were identified. All had an aggravation of their epilepsy in both clinical and EEG activities. OXC had been used because of an incorrect diagnosis of focal epilepsy or generalized tonic–clonic seizures (GTCSs) of undetermined origin (no syndromic classification of the epilepsy). Before OXC, only one patient had experienced a worsening of seizures with an inadequate drug (carbamazepine; CBZ). Four had juvenile myoclonic epilepsy, one had juvenile absence epilepsy, and one had IGE that could not be classified into a precise syndrome. OXC (dosage range, 300–1,200 mg/day) was used in monotherapy in all of them except for one patient. Aggravation consisted of a clear aggravation of myoclonic jerks (five cases) or de novo myoclonic jerks (one case). Three patients had exacerbation of absence seizures. One patient had worsened dramatically and had absence status, and one had de novo absences after OXC treatment. The effects of OXC on GTCSs were less dramatic, with no worsening in frequency in three and a slight increase in three. Conclusions OXC can be added to the list of antiepileptic drugs that can exacerbate myoclonic and absence seizures in IGE.

scholarly journals Women's Issues in the Treatment of Epilepsy

1998 ◽  
Vol 25 (S4) ◽  
pp. S19-S23 ◽  
Author(s):  
J. Bruni
Keyword(s):  
Sexual Dysfunction ◽  
Adverse Effects ◽  
Antiepileptic Drugs ◽  
Seizure Frequency ◽  
Seizure Control ◽  
Teratogenic Effects ◽  
New Agents ◽  
Advantages And Disadvantages ◽  
New Antiepileptic Drugs ◽  
Management Issues

ABSTRACT:Background:The management of women with epilepsy involves a number of important issues including conception control, sexual dysfunction and fertility, the effect of seizures on the fetus, possible changes in seizure frequency during pregnancy, potential teratogenic effects of antiepileptic drugs and management issues during pregnancy. The primary goal in the treatment of women with epilepsy remains optimal seizure control in the absence of unacceptable adverse effects. The advantages and disadvantages of the new antiepileptic drugs in women remain to be fully established but these new agents allow a wider choice for improved seizure control

scholarly journals The peculiarities of focal epilepsy in pregnant women

2017 ◽  
Vol 98 (5) ◽  
pp. 729-732 ◽  
Author(s):  
Sh Y Melikova
Keyword(s):  
Status Epilepticus ◽  
Sleep Deprivation ◽  
Pregnant Women ◽  
Antiepileptic Drug ◽  
Antiepileptic Drugs ◽  
Seizure Frequency ◽  
Focal Epilepsy ◽  
Average Duration ◽  
Convulsive Status Epilepticus

Aim. To investigate the peculiarities of focal epilepsy in pregnant women. Methods. 70 pregnant women with symptomatic focal epilepsy during the period from 2013 to 2017 were studied. Results. The average age at the onset of epilepsy was 18.2±0.6 years. The average duration of epilepsy by the time of pregnancy was 6.6±0.7 years. 15 (21.4±4.9%) women remained seizure-free during pregnancy. Seizures during pregnancy were observed in 55 (78.6±4.9%) women: seizure frequency increased in 22 (31.4±5.5%) cases, decreased in 17 (24.3±5.1%), remained unchanged in 8 (11.4±3.8%), in 8 (11.4±3.8%) women the onset of epilepsy occurred during pregnancy. 72.7% of women who were seizure-free for 1 year prior to pregnancy remained seizure-free during pregnancy. In 21 (40.4%) of 52 women with epilepsy diagnosed prior to pregnancy and treated with antiepileptic drugs, the increase of seizure frequency was observed, which can be explained by non-compliance with the regimen and therapy and sleep deprivation in 15 (71.4%) of them. Generalized convulsive status epilepticus during pregnancy was observed in 1 (1.4±1.4%) woman after a sudden withdrawal of the antiepileptic drug. Conclusion. The risk of seizures during pregnancy is lower in women who were seziure-free for 1 year prior to pregnancy; non-compliance with the regimen and therapy and sleep deprivation may lead to worsening of epilepsy during pregnancy.

scholarly journals Efficacy and tolerability of rufinamide in the treatment of epilepsy (experience of the Svt. Luka’s Institute of Child Neurology and Epilepsy)

2018 ◽  
Vol 13 (2) ◽  
pp. 7-19
Author(s):  
K. Yu. Mukhin ◽  
O. A. Pylaeva ◽  
M. Yu. Bobylova ◽  
N. V. Freydkova ◽  
L. Yu. Glukhova ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Side Effects ◽  
Antiepileptic Drugs ◽  
Seizure Frequency ◽  
Focal Epilepsy ◽  
Alternative Methods ◽  
Chromosomal Microarray ◽  
Study Cohort ◽  
Chromosomal Microarray Analysis ◽  
Drug Resistant

Background. Despite significant advances in epileptology, approximately one-third of epilepsy patients suffer from drug-resistant seizures. Numerous approaches are currently available to treat epilepsy; however, there are still many patients with treatment-resistant epilepsy, in whom surgical treatment is impossible and alternative methods (vagus nerve stimulation and ketogenic diet) are ineffective. Therefore, searching for novel effective antiepileptic drugs (AEDs) is crucial for these patients.Objective: analysis of own data on the efficacy and tolerability of rufinamide in patients with severe forms of epilepsy and seizures typical of Lennox–Gastaut syndrome (LGS).Materials and methods. The study included 31 patients aged between 4 and 26 years (mean age 7.5 years) that received rufinamide (inovelon). The study cohort comprised 21 males and 10 females. Fifteen patients were diagnosed with LGS, whereas 16 patients were diagnosed with structural focal epilepsy with a phenocopy of LGS. Five patients had an evolution of West syndrome to LGS. The majority of patients (n = 22) experienced predominantly axial tonic seizures and epileptic spasms that were considered as indications for introduction of rufinamide. All patients underwent electroencephalography, video-electroencephalography monitoring during wakefulness and sleep, magnetic resonance imaging (MRI) (including high-resolution MRI with special epilepsy protocols when indicated), genetic examination (tandem mass spectrometry, hereditary epilepsy gene panel test and chromosomal microarray analysis) when indicated, and laboratory tests to assess tolerability of antiepileptic drugs.Results. Good therapeutic effect (more than 50 % reduction in seizure frequency) was achieved in 14 (45.2 %) patients. A less than 50 % reduction in seizure frequency occurred in 5 (16.1 %) patients; in 2 of them seizures became shorter and milder without a significant reduction in their frequency. Rufinamide was ineffective in 9 (29 %) patients. Three (9.7 %) patients experienced aggravation (increased seizure frequency) after the introduction of rufinamide. Thus, treatment with rufinamide was effective in 19 (61.3 %) patients. Rufinamide was well tolerated by most of the patients. Side effects were observed in 6 (19 %) participants. Side effects (forced normalization) caused withdrawal of rufinamide in 1 (3.2 %) patient. Currently, 10 (32 %) patients continue to take rufinamide. Sixteen patients received rufinamide for <6 months, 17 patients – for >6 months, 5 patients – for >12 months, and 1 patient – for >2 years.Conclusion. Our findings are consistent with the results obtained by foreign authors in routine clinical practice. In our study, rufinamide was used only in patients with drug-resistant epilepsy that earlier received many of currently available AEDs (both in monotherapy and in combination with other drugs). All study participants were earlier treated with at least three different AEDs that were ineffective. Seven patients received more than 8 AEDs in various combinations. This initial drug resistance should be taken into account when analyzing the data, which can not be extrapolated to patients with unknown drug resistance. We assume that the early introduction of rufinamide (prior to the detection of drug resistance) might have yielded better results.

scholarly journals Padsevonil randomized Phase IIa trial in treatment-resistant focal epilepsy: a translational approach

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Pierandrea Muglia ◽  
Jonas Hannestad ◽  
Christian Brandt ◽  
Steven DeBruyn ◽  
Massimiliano Germani ◽  
...  
Keyword(s):  
Adverse Events ◽  
Antiepileptic Drug ◽  
Synaptic Vesicle ◽  
Antiepileptic Drugs ◽  
Seizure Frequency ◽  
Unmet Need ◽  
Proof Of Concept ◽  
Treatment Resistant ◽  
Synaptic Vesicle Protein ◽  
Translational Approach

Abstract Therapeutic options for patients with treatment-resistant epilepsy represent an important unmet need. Addressing this unmet need was the main factor driving the drug discovery program that led to the synthesis of padsevonil, a first-in-class antiepileptic drug candidate that interacts with two therapeutic targets: synaptic vesicle protein 2 and GABAA receptors. Two PET imaging studies were conducted in healthy volunteers to identify optimal padsevonil target occupancy corresponding to levels associated with effective antiseizure activity in rodent models. Optimal padsevonil occupancy associated with non-clinical efficacy was translatable to humans for both molecular targets: high (&gt;90%), sustained synaptic vesicle protein 2A occupancy and 10–15% transient GABAA receptor occupancy. Rational dose selection enabled clinical evaluation of padsevonil in a Phase IIa proof-of-concept trial (NCT02495844), with a single-dose arm (400 mg bid). Adults with highly treatment-resistant epilepsy, who were experiencing ≥4 focal seizures/week, and had failed to respond to ≥4 antiepileptic drugs, were randomized to receive placebo or padsevonil as add-on to their stable regimen. After a 3-week inpatient double-blind period, all patients received padsevonil during an 8-week outpatient open-label period. The primary endpoint was ≥75% reduction in seizure frequency. Of 55 patients randomized, 50 completed the trial (placebo n = 26; padsevonil n = 24). Their median age was 36 years (range 18–60), and they had been living with epilepsy for an average of 25 years. They were experiencing a median of 10 seizures/week and 75% had failed ≥8 antiepileptic drugs. At the end of the inpatient period, 30.8% of patients on padsevonil and 11.1% on placebo were ≥75% responders (odds ratio 4.14; P = 0.067). Reduction in median weekly seizure frequency was 53.7% and 12.5% with padsevonil and placebo, respectively (unadjusted P = 0.026). At the end of the outpatient period, 31.4% were ≥75% responders and reduction in median seizure frequency was 55.2% (all patients). During the inpatient period, 63.0% of patients on placebo and 85.7% on padsevonil reported treatment-emergent adverse events. Overall, 50 (90.9%) patients who received padsevonil reported treatment-emergent adverse events, most frequently somnolence (45.5%), dizziness (43.6%) and headache (25.5%); only one patient discontinued due to a treatment-emergent adverse event. Padsevonil was associated with a favourable safety profile and displayed clinically meaningful efficacy in patients with treatment-resistant epilepsy. The novel translational approach and the innovative proof-of-concept trial design maximized signal detection in a small patient population in a short duration, expediting antiepileptic drug development for the population with the greatest unmet need in epilepsy.

scholarly journals Investigation of the Roles of New Antiepileptic Drugs and Serum BDNF Levels in Efficacy and Safety Monitoring and Quality of Life: A Clinical Research

2020 ◽  
Vol 15 (1) ◽  
pp. 49-63
Author(s):  
Meral Demir ◽  
Emel O. Akarsu ◽  
Hava O. Dede ◽  
Nerses Bebek ◽  
Sevda O. Yıldız ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Antiepileptic Drugs ◽  
Focal Epilepsy ◽  
Education Level ◽  
Therapeutic Drug ◽  
Cross Sectional ◽  
New Antiepileptic Drugs ◽  
Healthy Participants ◽  
Serum Bdnf

Objective: We aimed to determine the therapeutic drug monitoring (TDM) features and the relation to Brain-Derived Neurotrophic Factor (BDNF) of frequently used new antiepileptic drugs (NADs) including lamotrigine (LTG), oxcarbazepine (OXC), zonisamide (ZNS) and lacosamide (LCM). Moreover, we investigated their effect on the quality of life (QoL). Methods: Eighty epileptic patients who had been using the NADs, and thirteen healthy participants were included in this cross-sectional study. The participants were randomized into groups. The QOLIE-31 test was used for the assessment of QoL. We also prepared and applied "Safety Test". HPLC method for TDM, and ELISA method for BDNF measurements were used consecutively. Results: In comparison to healthy participants, epileptic participants had lower marriage rate (p=0.049), education level (p˂0.001), alcohol use (p=0.002). BDNF levels were higher in patients with focal epilepsy (p=0.013) and in those with higher education level (p=0.016). There were negative correlations between serum BDNF levels and serum ZNS levels (p=0.042) with LTGpolytherapy, serum MHD levels (a 10-monohydroxy derivative of OXC, p=0.041) with OXCmonotherapy. There was no difference in BDNF according to monotherapy-polytherapy, drugresistant groups, regarding seizure frequency. There was a positive correlation between total health status and QoL (p˂0.001). QOLIE-31 overall score (OS) was higher in those with OXCmonotherapy (76.5±14.5). OS (p˂0.001), seizure worry (SW, p=0.004), cognition (C, p˂0.001), social function (SF, p˂0.001) were different in the main groups. Forgetfulness was the most common unwanted effect. Conclusion: While TDM helps the clinician to use more effective and safe NADs, BDNF may assist in TDM for reaching the therapeutic target in epilepsy.

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