Effects of antiseizure medications on alternative psychosis and strategies for their application

Forced normalization(FN)is a unique phenomenon that is often seen in the treatment of epilepsy.FN is characterized by abnormal mental behavior and disordered emotions in epilepsy patients despite a significantly improved electroencephalogram and successful seizure control;the occurrence of FN seriously affects patients’quality of life.The causes of FN include antiseizure medications(ASMs),epilepsy surgery and vagus nerve stimulation,with ASMs being the most common cause.However,with the timely reduction or discontinuation of ASMs and the use of antipsychotic drugs,the overall prognosis is good.Here,we perform an extensive review of the literature pertaining to FN,including its epidemiology,possible mechanisms,clinical features,treatment and prognosis.

Did pediatric drug development advance epilepsy treatment in young patients?It is time for new research goals

Modern drugs have changed epilepsy,which affects people of all ages.However,for young people with epilepsy,the framework of drug development has stalled.In the wake of the thalidomide catastrophe,the misconception emerged that for people<18 years of age drugs,including antiseizure medications(ASMs),need separate proof of efficacy and safety,overall called"pediatric drug development".For ASMs,this has changed to some degree.Authorities now accept that ASMs are effective in<18 years as well,but they still require"extrapolation of efficacy,"as if minors were another species.As a result,some of the pediatric clinical epilepsy research over the past decades was unnecessary.Even more importantly,this has hampered research on meaningful research goals.We do not need to confirm that ASMs work before as they do after the 18th birthday.Instead,we need to learn how to prevent brain damage in young patients by preventing seizures and optimize ASMs’uses.Herein we discuss how to proceed in this endeavor.

The pharmacological treatment of epilepsy:recent advances and future perspectives

The pharmacological armamentarium against epilepsy has expanded considerably over the last three decades,and currently includes over 30 different antiseizure medications.Despite this large armamentarium,about one third of people with epilepsy fail to achieve sustained seizure freedom with currently available medications.This sobering fact,however,is mitigated by evidence that clinical outcomes for many people with epilepsy have improved over the years.In particular,physicians now have unprecedented opportunities to tailor treatment choices to the characteristics of the individual,in order to maximize efficacy and tolerability.The present article discusses advances in the drug treatment of epilepsy in the last 5 years,focusing in particular on comparative effectiveness trials of second-generation drugs,the introduction of new pharmaceutical formulations for emergency use,and the results achieved with the newest medications.The article also includes a discussion of potential future developments,including those derived from advances in information technology,the development of novel precision treatments,the introduction of disease modifying agents,and the discovery of biomarkers to facilitate conduction of clinical trials as well as routine clinical management.

Managing reproductive problems in women with epilepsy of childbearing age

Girls and women constitute nearly 50%of all epilepsy cases.Apart from the disease symptoms,epilepsy and antiseizure medications(ASMs)may also affect the reproductive function,pregnancy and even the health of their offspring.Therefore,it is very important to identify and summarize the problems and risks for women with epilepsy(WWE)of childbearing age,and offer internationally recognized methods through multidisciplinary collaboration.In this review,we summarize the reproduction-related problems with WWE and propose multidisciplinary management by epileptologists,gynecologists and obstetricians,as well as other experts,from preconception to delivery.Large,multicenter registries are needed to advance our knowledge on new ASMs and their effects on WWE and their offspring.

Development of SV2A Ligands for Epilepsy Treatment:A Review of Levetiracetam,Brivaracetam,and Padsevonil

Epilepsy is a common neurological disorder that is primarily treated with antiseizure medications(ASMs).Although dozens of ASMs are available in the clinic,approximately 30%of epileptic patients have medically refractory seizures;other limitations in most traditional ASMs include poor tolerability and drug-drug interactions.Therefore,there is an urgent need to develop alternative ASMs.Levetiracetam(LEV)is a first-line ASM that is well tolerated,has promising efficacy,and has little drug-drug interaction.Although it is widely accepted that LEV acts through a unique therapeutic target synaptic vesicle protein(SV)2A,the molecular basis of its action remains unknown.Even so,the next-generation SV2A ligands against epilepsy based on the structure of LEV have achieved clinical success.This review highlights the research and development(R&D)process of LEV and its analogs,brivaracetam and padsevonil,to provide ideas and experience for the R&D of novel ASMs.