Use of Cannabidiol in the Treatment of Epilepsy: Efficacy and Security in Clinical Trials.
Silvestro Serena,Mammana Santa,Cavalli Eugenio,Bramanti Placido,Mazzon Emanuela
Molecules (Basel, Switzerland)
Cannabidiol (CBD) is one of the cannabinoids with non-psychotropic action, extracted from . CBD is a terpenophenol and it has received a great scientific interest thanks to its medical applications. This compound showed efficacy as anti-seizure, antipsychotic, neuroprotective, antidepressant and anxiolytic. The neuroprotective activity appears linked to its excellent anti-inflammatory and antioxidant properties. The purpose of this paper is to evaluate the use of CBD, in addition to common anti-epileptic drugs, in the severe treatment-resistant epilepsy through an overview of recent literature and clinical trials aimed to study the effects of the CBD treatment in different forms of epilepsy. The results of scientific studies obtained so far the use of CBD in clinical applications could represent hope for patients who are resistant to all conventional anti-epileptic drugs.
Vagus Nerve Stimulation for the Treatment of Epilepsy.
González Hernán F J,Yengo-Kahn Aaron,Englot Dario J
Neurosurgery clinics of North America
Vagus nerve stimulation (VNS) was the first neuromodulation device approved for treatment of epilepsy. In more than 20 years of study, VNS has consistently demonstrated efficacy in treating epilepsy. After 2 years, approximately 50% of patients experience at least 50% reduced seizure frequency. Adverse events with VNS treatment are rare and include surgical adverse events (including infection, vocal cord paresis, and so forth) and stimulation side effects (hoarseness, voice change, and cough). Future developments in VNS, including closed-loop and noninvasive stimulation, may reduce side effects or increase efficacy of VNS.
Treatment of Women With Epilepsy.
Continuum (Minneapolis, Minn.)
PURPOSE OF REVIEW:This article provides the latest information to guide practitioners in counseling and treating women with epilepsy. RECENT FINDINGS:There is an increasing body of literature on the multidirectional effects of sex hormones on seizure frequency and severity and of seizures altering areas of the brain involved in neuroendocrine function. Ongoing pregnancy outcome data from pregnancy registries and meta-analysis of observational studies have provided key information on the safety of using antiseizure medications during pregnancy and the risk to the fetus. SUMMARY:In treating and counseling women with epilepsy from puberty to menopause, it is important to understand the complex interactions of sex hormones, seizures, and antiseizure medications on reproductive health and pregnancy outcomes.
Recent advances in the neurosurgical treatment of pediatric epilepsy: JNSPG 75th Anniversary Invited Review Article
Roland Jarod,Smyth Matthew
Journal of neurosurgery. Pediatrics
The field of epilepsy surgery has seen tremendous growth in recent years. Innovative new devices have driven much of this growth, but some has been driven by revisions of existing products. Devices have also helped to rejuvenate existing procedures, as in the case of robotic assistance for electrode placement for stereo-electroencephalography, and these devices have brought significant attention along with their introduction. Other devices, such as responsive neurostimulators or laser interstitial thermal therapy systems, have introduced novel treatment modalities and broadened the surgical indications. Collectively, these advances are rapidly changing much of the landscape in the world of pediatric neurosurgery for medically refractory epilepsy. The foundations for indications for neurosurgical intervention are well supported in strong research data, which has also been expanded in recent years. In this article, the authors review advances in the neurosurgical treatment of pediatric epilepsy, beginning with trials that have repeatedly demonstrated the value of neurosurgical procedures for medically refractory epilepsy and following with several recent advances that are largely focused on less-invasive intervention.ABBREVIATIONS AED = antiepileptic drug; ANT = anterior nucleus of the thalamus; BOLD = blood oxygen level dependent; CCEP = cortico-cortical evoked potential; DBS = deep brain stimulation; ECoG = electrocorticography; ERSET = Early Randomized Surgical Epilepsy Trial; FCD = focal cortical dysplasia; HH = hypothalamic hamartoma; LITT = laser interstitial thermal therapy; RCT = randomized controlled trial; r-fMRI = resting-state functional MRI; RNS = responsive neurostimulation; SEEG = stereo-electroencephalography; VNS = vagus nerve stimulation.
Epilepsy in the Elderly: Treatment and Consideration of Comorbid Diseases.
Lee Sang Kun
Journal of epilepsy research
Epilepsy is the third most common neurological disorder affecting older adults after stroke and dementia, and the incidence of epilepsy is increasing rapidly in this population. A further increase in the incidence and prevalence of epilepsy is expected in aging societies. The establishment of a correct differential diagnosis between epilepsy and other seizure disorders that are common in the elderly is crucial. The symptoms of seizures in the elderly may be different from those in younger populations. The diagnosis is difficult, probably because of nonspecific characteristics, short-term symptoms, and absence of witnesses. There are three important issues in the treatment of epilepsy in the elderly: changes in pharmacokinetic parameters, polytherapy (including non-antiepileptic and antiepileptic drugs), and susceptibility to adverse drug effects. Antiepileptic drugs (AEDs) with fewer adverse effects, including cognitive effects, and AEDs without significant pharmacokinetic drug interactions are needed. Several studies found that stroke was strongly associated with a high incidence of early seizures and epilepsy. Stroke is also one of the major causes of status epilepticus. Cortical involvement and large lesions are strongly associated with the development of seizures and epilepsy. The severity of the initial neurological deficit is a strong clinical predictor of seizures after ischemic stroke. The optimal quality of life of dementia patients cannot be achieved without a proper diagnosis of coexisting epilepsy.
Neuroinflammatory pathways as treatment targets and biomarkers in epilepsy.
Vezzani Annamaria,Balosso Silvia,Ravizza Teresa
Nature reviews. Neurology
Epilepsy is a chronic neurological disease characterized by an enduring propensity for generation of seizures. The pathogenic processes of seizure generation and recurrence are the subject of intensive preclinical and clinical investigations as their identification would enable development of novel treatments that prevent epileptic seizures and reduce seizure burden. Such treatments are particularly needed for pharmacoresistant epilepsies, which affect ~30% of patients. Neuroinflammation is commonly activated in epileptogenic brain regions in humans and is clearly involved in animal models of epilepsy. An increased understanding of neuroinflammatory mechanisms in epilepsy has identified cellular and molecular targets for new mechanistic therapies or existing anti-inflammatory drugs that could overcome the limitations of current medications, which provide only symptomatic control of seizures. Moreover, inflammatory mediators in the blood and molecular imaging of neuroinflammation could provide diagnostic, prognostic and predictive biomarkers for epilepsy, which will be instrumental for patient stratification in future clinical studies. In this Review, we focus on our understanding of the IL-1 receptor-Toll-like receptor 4 axis, the arachidonic acid-prostaglandin cascade, oxidative stress and transforming growth factor-β signalling associated with blood-brain barrier dysfunction, all of which are pathways that are activated in pharmacoresistant epilepsy in humans and that can be modulated in animal models to produce therapeutic effects on seizures, neuronal cell loss and neurological comorbidities.
[Exploring Molecular Targets for Epilepsy Treatment from the Perspective of Neuronal Homeostasis].
Nagai Taku,Shan Wei,Yamada Kiyofumi
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
Brain function is controlled by the balance between the excitatory and inhibitory systems. If this balance is disrupted and the excitatory system dominates, convulsions or epileptic seizures are induced. Neuronal hyperexcitability in the brain leads to marked changes in the function of the neurons, which adversely affect the stability of the neural network. Many of the currently used antiepileptic drugs are symptomatic treatments that suppress the electrical hyperexcitability of the cerebrum. Although patients with epilepsy should continuously take antiepileptic drugs to control their seizures, approximately 20% of patients are drug resistant. The brain has the ability to control neuronal functions within acceptable limits while it maintains the amount of synaptic inputs that form the basis of information accumulation. Neuronal self-regulation is known as homeostatic scaling by which the intensity of all excitatory synapses is suppressed when neuronal excitability is increased. However, the molecular mechanisms of homeostatic scaling and their pathophysiological significance in vivo remain unclear. Repeated treatment with a subconvulsive dosage of pentylenetetrazol (PTZ), a γ-aminobutyric acid (GABA) receptor antagonist, is known to induce kindling in mice, which is a common animal model used to study epilepsy. We found that PTZ-induced kindling was potentiated in mice deficient in the transcription factor neuronal PAS domain protein 4 (Npas4), the expression of which is immediately induced in response to neuronal activity. At this symposium, we will discuss the possibility of Npas4 as a novel target molecule for epilepsy treatment.
Current and emerging drug therapies for the treatment of depression in adults with epilepsy.
Mula Marco,Sander Josemir W
Expert opinion on pharmacotherapy
INTRODUCTION:Depression is the most frequent psychiatric comorbidity among people with epilepsy. It can impact on quality of life and increases the risk of morbidity and premature mortality. AREAS COVERED:The authors review the available data on current and emerging drug treatments for depression in epilepsy. Sources have been identified through Medline/PubMed searches while ongoing clinical trials have been identified through a ClinicalTrials.gov search EXPERT OPINION:SSRIs are the drug class with the largest amount of data. Though promising, the level of evidence provided by these studies is still low as the majority have relevant methodological limitations. Antiepileptic drugs under development have the unique opportunity to be of multi-use in the treatment of epilepsy and depression. The serotoninergic system has already been identified as a potential area of interest, but new targets are still needed in epilepsy and depression. For this reason, it is important that basic scientists working on these two conditions develop collaborative projects and integrate findings.
Epilepsy in Children: From Diagnosis to Treatment with Focus on Emergency.
Minardi Carmelo,Minacapelli Roberta,Valastro Pietro,Vasile Francesco,Pitino Sofia,Pavone Piero,Astuto Marinella,Murabito Paolo
Journal of clinical medicine
Seizures are defined as a transient occurrence of signs and symptoms due to the abnormal, excessive, or synchronous neuronal activity in the brain characterized by abrupt and involuntary skeletal muscle activity. An early diagnosis, treatment, and specific medical support must be performed to prevent Status Epilepticus (SE). Seizure onset, especially in the child population, is related to specific risk factors like positive family history, fever, infections, neurological comorbidity, premature birth, mother's alcohol abuse, and smoking in pregnancy. Early death risk in children without neurological comorbidity is similar to the general population. Diagnosis is generally based on the identification of continuous or recurrent seizures but Electroencephalogram (EEG) evaluation could be useful if SE condition is suspected. The main goal of therapy is to counteract the pathological mechanism which occurs in SE before neural cells are irreversibly damaged. According to the latest International Guidelines and Recommendations of seizure related diseases, a schematic and multi-stage pharmacological and diagnostic approach is proposed especially in the management of SE and its related causes in children. First measures should focus on early and appropriate drugs administration at adequate dosage, airway management, monitoring vital signs, Pediatric Intensive Care Unit (PICU) admission, and management of parent anxiety.
Pharmacological treatment of attention-deficit/hyperactivity disorder in children and adolescents with epilepsy.
Attention-deficit/hyperactivity disorder (ADHD) is the most frequent comorbidities in children with epilepsy with an increased risk of other psychiatric comorbidities and academic underachievement. In children with epilepsy, the attentive form is the most common clinical presentation in pediatric epilepsies. A systemic review and a consensus from the ILAE have been recently published on diagnosis, screening and management of ADHD in children with epilepsy. We give an overview of the pharmacological treatment of ADHD in children with epilepsy based on the lecture given at the International League Against Epilepsy (ILAE) French Chapter meeting, (October 2018, Lyon). Although only class II and class III studies are available, methylphenidate is the most appropriate pharmacological option for the treatment of ADHD in children with epilepsy with a limited risk of seizure worsening. The medical treatment should be used in combination of the global management including optimal antiepileptic drug treatment avoiding polytherapy, management of psychiatric comorbidities and support at school.
Epilepsy treatment in the elderly.
Biraben Arnaud,De Clerck Lucie,Nica Anca
Geriatrie et psychologie neuropsychiatrie du vieillissement
The population is aging in all countries. The incidence of epilepsy increases with age, leading to an increase in the number of elderly epileptic patients. In addition to the diagnostic problems specific to this population, there are particular treatment difficulties for these age groups. Indeed, in addition to the physiological aging that modifies the metabolism of many drugs is added frequent comorbidities and consequently frequent co-medications. These comorbidities can be neurological, psychiatric, degenerative, but also cardiovascular, renal or hepatic... The availability of many new anti-epileptic drugs has not been very effective in comparison to the old ones. Studies show that new molecules are better tolerated and associated with a better compliance. They are also easier to use, some need just a single daily dose, systematic biological control is not necessary, and they have fewer interactions with co-medications than older anti-epileptic drugs. Thus, at present, these advances make the management of epilepsy more complex but also allow a better personalization of the treatment adapted to a particular patient in this fragile population.
Treatment of psychoses in patients with epilepsy: an update.
Agrawal Niruj,Mula Marco
Therapeutic advances in psychopharmacology
Psychotic disorders represent a relatively rare but serious comorbidity in epilepsy. Current epidemiological studies are showing a point prevalence of 5.6% in unselected samples of people with epilepsy going up to 7% in patients with temporal lobe epilepsy, with a pooled odds ratio of 7.8 as compared with the general population. This is a narrative review of the most recent updates in the management of psychotic disorders in epilepsy, taking into account the clinical scenarios where psychotic symptoms occur in epilepsy, interactions with antiepileptic drugs (AEDs) and the risk of seizures with antipsychotics. Psychotic symptoms in epilepsy can arise in a number of different clinical scenarios from peri-ictal symptoms, to chronic interictal psychoses, comorbid schizophrenia and related disorders to the so-called forced normalization phenomenon. Data on the treatment of psychotic disorders in epilepsy are still limited and the management of these problems is still based on individual clinical experience. For this reason, guidelines of treatment outside epilepsy should be adopted taking into account epilepsy-related issues including interactions with AEDs and seizure risk. Second-generation antipsychotics, especially risperidone, can represent a reasonable first-line option because of the low propensity for drug-drug interactions and the low risk of seizures. Quetiapine is burdened by a clinically significant pharmacokinetic interaction with enzyme-inducing drugs leading to undetectable levels of the antipsychotic, even for dosages up to 700 mg per day.
Review: Neuroinflammatory pathways as treatment targets and biomarker candidates in epilepsy: emerging evidence from preclinical and clinical studies.
van Vliet E A,Aronica E,Vezzani A,Ravizza T
Neuropathology and applied neurobiology
Accumulating evidence indicates an important pathophysiological role of brain inflammation in epilepsy. In this review, we will provide an update of specific inflammatory pathways that have been proposed to be crucial in the underlying molecular mechanisms of epilepsy, including the interleukin-1 receptor/toll-like receptor signalling, cyclooxygenase-2, tumour necrosis factor-alpha, complement signalling and chemokines. Furthermore, by drawing on evidence from preclinical and clinical studies we will discuss the potential of these signalling pathways targets for novel therapeutic interventions that control drug-resistant seizures or have disease-modifying effects. Finally, we will assess the use of these inflammatory pathways as potential biomarkers for the development of epilepsy or to measure the effectiveness of therapeutic interventions.
A meta-analysis of randomized controlled trials on levetiracetam in the treatment of pediatric patients with epilepsy.
Zhang Lanlan,Wang Chengzhong,Li Wei
Neuropsychiatric disease and treatment
Objective:To evaluate clinical efficacy, safety, and tolerability of levetiracetam as mono- or adjunctive therapy in the treatment of children and adolescents with epilepsy. Materials and methods:We performed a meta-analysis of randomized controlled trials published from January 2007 to December 2016 in the databases Web of Science, Medline, Embase, Cochrane Library, and PubMed, Bing, Baidu, Google Scholar, Chinese National Knowledge Infrastructure (CNKI), and Wanfang Data. All of the studies eligible were compared for the efficacy, safety, and tolerability of levetiracetam with other antiepileptic drugs (AEDs) in epilepsy. Results:Thirteen randomized controlled trials on a total of 1,013 patients met the inclusion criteria in present study. Compared with other AEDs (oxcarbazepine, valproate, sulthiame, carbamazepine, and placebo), we found that levetiracetam had a comparable seizure-free rate (RR 1.16, 95% CI 1.03-1.31; =0.30). Regarding seizure-frequency reduction ≥50% from baseline, levetiracetam also seemed equivalent to other AEDs (RR 1.08, 95% CI 1.01-1.16; =0.35). In spite of patients treated with levetiracetam having a lower incidence of side effects compared with patients treated with other AEDs (RR 0.90, 95% CI 0.77-1.06), the difference between them was minute and not statistically significant (=0.22). Conclusion:Based on this meta-analysis, it seemed that levetiracetam had comparable effects concerning efficacy, tolerability, and adverse events. Nevertheless, 13 studies were insufficient to draw a conclusion that levetiracetam is effective as mono- and adjunctive therapy for all types of epilepsy syndromes and seizures. Larger-sample and more well-designed trials are needed to justify the widespread use of levetiracetam in the treatment of children and adolescents.
Diagnosis and Surgical Treatment of Drug-Resistant Epilepsy.
Anyanwu Chinekwu,Motamedi Gholam K
Despite appropriate trials of at least two antiepileptic drugs, about a third of patients with epilepsy remain drug resistant (intractable; refractory). Epilepsy surgery offers a potential cure or significant improvement to those with focal onset drug-resistant seizures. Unfortunately, epilepsy surgery is still underutilized which might be in part because of the complexity of presurgical evaluation. This process includes classifying the seizure type, lateralizing and localizing the seizure onset focus (epileptogenic zone), confirming the safety of the prospective brain surgery in terms of potential neurocognitive deficits (language and memory functions), before devising a surgical plan. Each one of the above steps requires special tests. In this paper, we have reviewed the process of presurgical evaluation in patients with drug-resistant focal onset epilepsy.
Epidemiologist's view: Addressing the epilepsy surgery treatment gap with minimally-invasive techniques.
Schiltz Nicholas K,Fernandez-Baca Vaca Guadalupe
Despite the fact that epilepsy surgery is both safe and effective, a considerable "surgical treatment gap" remains in that most persons who are eligible for surgery do not receive it. It has been argued that epilepsy surgery is one of the most underutilized of all accepted medical treatments in the world. In this article, we review the epidemiology of the epilepsy surgery treatment gap, and consider the role minimally-invasive epilepsy surgery may play in reducing this gap.
Extended-release drug formulations for the treatment of epilepsy.
Brandt Christian,May Theodor W
Expert opinion on pharmacotherapy
INTRODUCTION:Extended-release (ER) preparations are either available or have been tested for several antiepileptic drugs (AEDs). Indeed, they may be helpful in improving efficacy, tolerability, adherence, compared to the corresponding immediate release (IR) preparations available. The use of ER preparations has been advocated in women of childbearing age and is - depending on the drug - especially helpful in patients who are treated in combination with enzyme inducing AEDs as well as in children. AREAS COVERED:Clinical and pharmacokinetic studies on ER formulations of AEDs were identified by a PubMed literature research. Further references were added from the authors' personal knowledge and from the reference lists of the identified studies. Reviews and expert commentaries were included, where necessary. EXPERT OPINION:Unfortunately, studies providing direct comparisons of ER and IR formulations of a given drug are only available for a handful of drugs. ER preparations are especially helpful in drugs with a short elimination half-life and concentration-depending efficacy and tolerability.
Surgical Treatment of Lesional Mesial Temporal Lobe Epilepsy.
Chong Sangjoon,Phi Ji Hoon,Lee Ji Yeoun,Kim Seung-Ki
Journal of epilepsy research
Lesional mesial temporal lobe epilepsy (mTLE) concerns a lesion other than mesial hippocampal sclerosis present in the mesial temporal lobe and causing seizures. The lesions are usually composed of focal cortical dysplasia (FCD) or are tumorous. These are good candidates for surgical treatment. Sometimes, it is difficult to distinguish between tumors and FCD and to determine the extent of required removal. C-methionine positron emission tomography (PET) is helpful in differentiating lesions before surgery in lesional mTLE. In C-methionine PET imaging, tumors show a hot uptake, whereas FCD does not. In case of tumorous conditions, the removal of only specific lesions may be considered because the seizure outcome is dependent on complete excision of the tumor. There are several ways to safely access mesial temporal structures. The transsylvian-transcisternal approach is a good way to access the mesial structures while preserving the lateral and basal temporal structures. Actual lesions associated with epileptogenesis in FCD may be larger than they appear on magnetic resonance imaging. For this reason, evaluations to locate sufficient epileptogenic foci, including invasive studies, should be completed for FCD, and epilepsy surgery should be performed according to these results. Regardless, the ultimate goal of all epilepsy surgeries is to maximize seizure control while maintaining neurological function. Therefore, a tailored approach based on the properties of the lesion is needed.
A review of treatment options for behavioural manifestations of clinical anxiety as a comorbidity in dogs with idiopathic epilepsy.
Watson F,Rusbridge C,Packer R M A,Casey R A,Heath S,Volk H A
Veterinary journal (London, England : 1997)
Psychiatric comorbidities affect a large percentage of people with epilepsy and have a detrimental impact on their quality of life. Recently, behavioural comorbidities, with similar characteristics to human psychiatric diseases, have been identified in dogs with idiopathic epilepsy. In particular, behaviours motivated by the fear-anxiety emotional system have been found to be associated with the occurrence of idiopathic epilepsy in both dogs receiving anti-epileptic drugs, and drug-naïve dogs. There has been little research into the relationship between epilepsy and behavioural signs, and even less into potential treatment protocols. The following article will review available literature from human medicine to describe the current state of knowledge about the bi-directional relationship between anxiety and epilepsy, draw parallels from reported anxiogenic and anxiolytic properties of anti-epileptic drugs and attempt to provide pharmaceutical and behavioural guidance for veterinary patients with epilepsy and comorbid anxiety.
Cannabis for the Treatment of Epilepsy: an Update.
Gaston Tyler E,Szaflarski Jerzy P
Current neurology and neuroscience reports
PURPOSE OF REVIEW:For millennia, there has been interest in the use of cannabis for the treatment of epilepsy. However, it is only recently that appropriately powered controlled studies have been completed. In this review, we present an update on the research investigating the use of cannabidiol (CBD), a non-psychoactive component of cannabis, in the treatment of epilepsy. RECENT FINDINGS:While the anticonvulsant mechanism of action of CBD has not been entirely elucidated, we discuss the most recent data available including its low affinity for the endocannabinoid receptors and possible indirect modulation of these receptors via blocking the breakdown of anandamide. Additional targets include activation of the transient receptor potential of vanilloid type-1 (TRPV1), antagonist action at GPR55, targeting of abnormal sodium channels, blocking of T-type calcium channels, modulation of adenosine receptors, modulation of voltage-dependent anion selective channel protein (VDAC1), and modulation of tumor necrosis factor alpha release. We also discuss the most recent studies on various artisanal CBD products conducted in patients with epilepsy in the USA and internationally. While a high percentage of patients in these studies reported improvement in seizures, these studies were either retrospective or conducted via survey. Dosage/preparation of CBD was either unknown or not controlled in the majority of these studies. Finally, we present data from both open-label expanded access programs (EAPs) and randomized placebo-controlled trials (RCTs) of a highly purified oral preparation of CBD, which was recently approved by the FDA in the treatment of epilepsy. In the EAPs, there was a significant improvement in seizure frequency seen in a large number of patients with various types of treatment-refractory epilepsy. The RCTs have shown significant seizure reduction compared to placebo in patients with Dravet syndrome and Lennox-Gastaut syndrome. Finally, we describe the available data on adverse effects and drug-drug interactions with highly purified CBD. While this product is overall well tolerated, the most common side effects are diarrhea and sedation, with sedation being much more common in patients taking concomitant clobazam. There was also an increased incidence of aspartate aminotransferase and alanine aminotransferase elevations while taking CBD, with many of the patients with these abnormalities also taking concomitant valproate. CBD has a clear interaction with clobazam, significantly increasing the levels of its active metabolite N-desmethylclobazam in several studies; this is felt to be due to CBD's inhibition of CYP2C19. EAP data demonstrate other possible interactions with rufinamide, zonisamide, topiramate, and eslicarbazepine. Additionally, there is one case report demonstrating need for warfarin dose adjustment with concomitant CBD. Understanding of CBD's efficacy and safety in the treatment of TRE has expanded significantly in the last few years. Future controlled studies of various ratios of CBD and THC are needed as there could be further therapeutic potential of these compounds for patients with epilepsy.
Safety and tolerability profile of new antiepileptic drug treatment in children with epilepsy.
Moavero Romina,Pisani Laura Rosa,Pisani Francesco,Curatolo Paolo
Expert opinion on drug safety
INTRODUCTION:Treatment of pediatric epilepsy requires a careful evaluation of the safety and tolerability profile of antiepileptic drugs (AEDs) to avoid or minimize as much as possible adverse events (AEs) on various organs, hematological parameters, and growth, pubertal, motor, cognitive and behavioral development. AREAS COVERED:Treatment-emergent AEs (TEAEs) reported in the literature 2000-2018 regarding second- and third-generation AEDs used in the pediatric age, with exclusion of the neonatal period that exhibits specific peculiarities, have been described on the basis of their frequency, severity/tolerability, and particular association with a given AED. EXPERT OPINION:Somnolence/sedation and behavioral changes, like irritability and nervousness, are among the most commonly observed TEAEs associated with almost all AEDs. Lamotrigine, Gabapentin, Oxcarbazepine, and Levetiracetam appear to be the best-tolerated AEDs with a ≤2% withdrawal rate, while Tiagabine and Everolimus are discontinued in up to >20% of the patients because of intolerable TEAEs. For some AEDs, literature data are scanty to draw a high-level evidence on their safety and tolerability profile. The reasons are: insufficient population size, short duration of treatments, or lack of controlled trials. A future goal is that of identifying clearer, easier, and more homogeneous methodological strategies to facilitate AED testing in pediatric populations.
Pharmacological treatment of anxiety disorders in adults with epilepsy.
Expert opinion on pharmacotherapy
INTRODUCTION:Anxiety disorders represent one of the most frequently encountered comorbidities in patients with epilepsy, affecting the quality of life and increasing, morbidity, mortality, and healthcare costs. However, they are still underdiagnosed and undertreated. AREAS COVERED:This is a narrative review of the pharmacological treatment of anxiety disorders in adult patients with epilepsy discussing also major issues regarding pathophysiology and diagnosis. EXPERT OPINION:There are a lack of studies concerning the treatment of anxiety disorders in epilepsy, which is a serious gap in the literature. There is an urgent need for treatment and outcome data in order to provide information to patients. Current evidence outside epilepsy focuses on Selective Serotonin Reuptake Inhibitors and Serotonin Noradrenalin Reuptake Inhibitor with strong evidence especially for the acute and long-term treatment of Generalized Anxiety Disorder and Social Anxiety Disorder. Although it is reasonable to adopt treatment guidelines outside of epilepsy, it is completely unknown whether anxiety disorders in people with epilepsy have the same response and remission rates observed outside epilepsy. Future research strategies for new drug treatments in epilepsy will probably take comorbidities into account. At this point, pregabalin and buspirone represent an interesting starting point for the development of new compounds potentially indicated in both conditions.
Treatment of epilepsy - towards precision.
Leach John Paul
Epilepsy was among the first disease areas to begin to apply principles of precision medicine to its treatment. This review looks at the role of investigation in ensuring the safety and effectiveness of antiepileptic drug treatment. Using sound principles, we can see that the use of genetic testing will advance treatment of epilepsy in reducing harm and adverse effects and enhancing efficacy.
Epilepsy in patients with autism: links, risks and treatment challenges.
Besag Frank Mc
Neuropsychiatric disease and treatment
Autism is more common in people with epilepsy, approximately 20%, and epilepsy is more common in people with autism with reported rates of approximately 20%. However, these figures are likely to be affected by the current broader criteria for autism spectrum disorder (ASD), which have contributed to an increased prevalence of autism, with the result that the rate for ASD in epilepsy is likely to be higher and the figure for epilepsy in ASD is likely to be lower. Some evidence suggests that there are two peaks of epilepsy onset in autism, in infancy and adolescence. The rate of autism in epilepsy is much higher in those with intellectual disability. In conditions such as the Landau-Kleffner syndrome and nonconvulsive status epilepticus, the epilepsy itself may present with autistic features. There is no plausible mechanism for autism causing epilepsy, however. The co-occurrence of autism and epilepsy is almost certainly the result of underlying factors predisposing to both conditions, including both genetic and environmental factors. Conditions such as attention deficit hyperactivity disorder, anxiety and sleep disorders are common in both epilepsy and autism. Epilepsy is generally not a contraindication to treating these conditions with suitable medication, but it is important to take account of relevant drug interactions. One of the greatest challenges in autism is to determine why early childhood regression occurs in perhaps 25%. Further research should focus on finding the cause for such regression. Whether epilepsy plays a role in the regression of a subgroup of children with autism who lose skills remains to be determined.