Deciding When Less Is More: The Crossroads of Withdrawing Antiepileptic Drugs.
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ABSTRACT:
SUBMITTER: Ruiz NV
PROVIDER: S-EPMC5887331 | biostudies-literature | 2018 Jan-Feb
REPOSITORIES: biostudies-literature
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Deciding When Less Is More: The Crossroads of Withdrawing Antiepileptic Drugs.
Epilepsy currents 20180101 1
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Project description: Not available
| S-EPMC1570847 | biostudies-literature
Project description:There are now 24 antiepileptic drugs (AEDs) approved for use in epilepsy in the United States by the Food and Drug Administration. A literature search was conducted using PubMed, MEDLINE, and Google for all English-language articles that discuss newly approved AEDs and the use of AEDs in epilepsy in the United States from January 1, 2008, through December 31, 2011. Five new agents were identified that have come onto the market within the past 2 years. Moreover, 3 trends involving AEDs have become clinically important and must be considered by all who treat patients with epilepsy. These trends include issues of generic substitution of AEDs, pharmacogenomics predicting serious adverse events in certain ethnic populations, and the issue of the suicide risk involving the entire class of AEDs. This article discusses the most recent AEDs approved for use in the United States and the 3 important trends shaping the modern medical management of epilepsy.
| S-EPMC3538494 | biostudies-literature
Project description:The goal of pharmacogenetic research is to assist clinicians in predicting patient response to medications when genetic variations are identified. The pharmacogenetic variation of antiepileptic drug response and side effects has yielded findings that have been included in drug labeling and guidelines. The goal of this review is to provide a brief overview of the pharmacogenetic research on antiepileptic drugs. It will focus on findings that have been included in drug labeling, guidelines, and candidate pharmacogenetic variation. Overall, several genes have been included in guidelines by national and international organizations; however, much work is needed to implement and evaluate their use in clinical settings.
| S-EPMC6009246 | biostudies-literature
Project description:ObjectiveTo evaluate the real world durability of contemporary ART for treatment-naïve people living with HIV (PLWH).DesignA retrospective follow-up study in a multisite cohort.MethodsThis study of the CNICS (CFAR Network of Integrated Clinical Systems) cohort integrates data from eight Center for AIDS Research (CFARs). PLWH initiating ART between 2007 and 2014 were included. Durability was defined as time from the initiation until discontinuation/modification using Kaplan-Meier survival curves. Cox Proportional Hazards measured associations with various sociodemographic and clinical characteristics.ResultsAmong 5373 PLWH, the initial regimen was modified in 2285 (43%) patients. Efavirenz/emtricitabine/tenofovir (n = 2173, 40%) was the most commonly prescribed initial ART regimen; elvitegravir/cobicistat/emtricitabine/tenofovir became more common after 2012. Median durability for all regimens was 48.6 months. There were statistically significant differences in median durability for NNRTI, InSTI, and protease inhibitor-based regimens, which lasted 61, 44, and 32 months, respectively. Female sex (aHR = 1.4; 95% CI 1.2-1.6), intravenous drug use (aHR = 1.6; 95% CI 1.3-1.9), and CD4 cell count less than 200 cells/μl (aHR = 1.2; 95% CI 1.1-1.3) were significantly associated with regimen modification. Compared with InSTI, those receiving an InSTI/protease inhibitor (aHR = 2.7; 95% CI 2.0-3.7) or protease inhibitor-based ART (aHR = 1.9; 95% CI 1.6-2.2) were significantly more likely to be modified; but those receiving NNRTI (aHR = 1.1; 95% CI 0.9-1.3) were not.ConclusionIn treatment-naive PLWH, NNRTI and InSTI-based ART were most durable, relative to protease inhibitor and InSTI/protease inhibitor-based ART, and were least likely to be modified/discontinued. A greater understanding of reasons for regimen modification/discontinuation is needed to analyze contemporary regimen durability.
| S-EPMC6604808 | biostudies-literature
Project description:Epilepsy is the most common neurological disorder which significantly affects the quality of life and poses a health as well as economic burden on society. Epilepsy affects approximately 70 million people in the world. The present article reviews the scientific rationale, brief pathophysiology of epilepsy and newer antiepileptic drugs which are presently under clinical development. We have searched the investigational drugs using the key words 'antiepileptic drugs,' 'epilepsy,' 'Phase I,' 'Phase II' and 'Phase III' in American clinical trial registers (clinicaltrials.gov), the relevant published articles using National Library of Medicine's PubMed database, company websites and supplemented results with a manual search of cross-references and conference abstracts. This review provides a brief description about the antiepileptic drugs which are targeting different mechanisms and the clinical development status of these drugs. Besides the presence of old as well as new AEDs, still there is a need of new drugs or the modified version of old drugs in order to make affected people free of seizures. An optimistic approach should be used to translate the success of preclinical testing to clinical practice. There is an urgent need to improve animal models and to explore new targets with better understanding in order to develop the novel drugs with more efficacy and safety.
| S-EPMC5803110 | biostudies-other
Project description:Background: Pharmacological evaluation of antiepileptic drugs (AEDs) using mammalian animals takes long time and is expensive. The zebrafish is a species commonly used to study brain functions, neurological diseases, and drug toxicity, and attracts more attention as an alternative animal model to substitute or supplement mammalian animals in drug development. Electroencephalogram (EEG) is a key indicator for diagnosing brain diseases such as epilepsy, by directly measuring the brain activity. We propose a novel method for pharmacological evaluation of AEDs based on EEG from adult zebrafish, which allows researchers to select more clinically valuable drugs at the early stage of AED screening. Methods: To evaluate the efficacy of AEDs, zebrafish EEG signals were measured after administering six AEDs (valproate acid, gabapentin, ethosuximide, oxcarbazepine, tiagabine, and topiramate) at various doses to pentylenetetrazol (PTZ)-induced seizure models. The change in seizure activity was investigated according to doses. The antiepileptic effect was determined by observing a significant decrease in at least one out of three indicators of the number, total duration, and mean duration of ictal events. Results: Using EEG signals from adult zebrafish, antiepileptic effects were observed with all six AEDs. Among them, antiepileptic effects depending on dose were confirmed with valproate acid, gabapentin, ethosuximide, and tiagabine. Moreover, the 50% effective doses (ED50) of valproate acid and tiagabine were determined based on zebrafish EEG for the first time, indicating that the quantitative inter-species comparison of the AED efficacy is possible between zebrafish and mammals such as rodents. Significance: The results show that zebrafish can be used to effectively and quantitatively evaluate the efficacy of AEDs based on EEG, the same method to evaluate antiepileptic effects in mammals, suggesting that the proposed method can contribute in reducing the cost and duration of search for AEDs and thus accelerate the drug development cycles.
| S-EPMC9772616 | biostudies-literature
Project description:ImportanceRecent studies have highlighted an association between epilepsy and Parkinson disease (PD). The role of antiepileptic drugs (AEDs) has not been explored.ObjectiveTo investigate the association between AEDs and incident PD.Design, setting, and participantsThis nested case-control study started collecting data from the UK Biobank (UKB) in 2006, and data were extracted on June 30, 2021. Individuals with linked primary care prescription data were included. Cases were defined as individuals with a Hospital Episode Statistics (HES)-coded diagnosis of PD. Controls were matched 6:1 for age, sex, race and ethnicity, and socioeconomic status. Prescription records were searched for AEDs prescribed prior to diagnosis of PD. The UKB is a longitudinal cohort study with more than 500 000 participants; 45% of individuals in the UKB have linked primary care prescription data. Participants living in the UK aged between 40 and 69 years were recruited to the UKB between 2006 and 2010. All participants with UKB-linked primary care prescription data (n = 222 106) were eligible for enrollment in the study. Individuals with only a self-reported PD diagnosis or missing data for the matching variables were excluded. In total, 1477 individuals were excluded; 49 were excluded due to having only self-reported PD, and 1428 were excluded due to missing data.ExposuresExposure to AEDs (carbamazepine, lamotrigine, levetiracetam, and sodium valproate) was defined using routinely collected prescription data derived from primary care.Main outcomes and measuresOdds ratios and 95% CIs were calculated using adjusted logistic regression models for individuals prescribed AEDs before the first date of HES-coded diagnosis of PD.ResultsIn this case-control study, there were 1433 individuals with an HES-coded PD diagnosis (cases) and 8598 controls in the analysis. Of the 1433 individuals, 873 (60.9%) were male, 1397 (97.5%) had their race and ethnicity recorded as White, and their median age was 71 years (IQR, 65-75 years). An association was found between AED prescriptions and incident PD (odds ratio, 1.80; 95% CI, 1.35-2.40). There was a trend for a greater number of prescription issues and multiple AEDs being associated with a greater risk of PD.Conclusions and relevanceThis study, the first to systematically look at PD risk in individuals prescribed the most common AEDs, to our knowledge, found evidence of an association between AEDs and incident PD. With the recent literature demonstrating an association between epilepsy and PD, this study provides further insights.
| S-EPMC9857018 | biostudies-literature
Project description:Epilepsy is one of the most frequent chronic neurologic disorders that affects nearly 1% of the population worldwide, especially in developing countries. Currently, several antiepileptic drugs (AEDs) are available for its therapy, and although the prognosis is good for most patients, 20%-30% amongst them do not reach seizure freedom. Numerous factors may explain AED-resistance such as sex, age, ethnicity, type of seizure, early epilepsy onset, suboptimal dosing, poor drug compliance, alcohol abuse, and in particular, genetic factors. Specifically, the interindividual differences in drug response can be caused by single nucleotide polymorphisms (SNPs) in genes encoding for drug efflux transporters, for the brain targets of AEDs, and for enzymes involved in drug metabolism. In this review, we used the PubMed database to retrieve studies that assessed the influence of SNPs on the pharmacokinetic (PK), pharmacodynamic (PD), and efficacy of new antiepileptic drugs. Our results showed that polymorphisms in the ABCB1, ABCC2, UGT1A4, UGT2B7, UGT2B15, CYP2C9, and CYP2C19 genes have an influence on the PK and efficacy of AEDs, suggesting that a genetic pre-evaluation of epileptic patients could help clinicians in prescribing a personalized treatment to improve the efficacy and the safety of the therapy.
| S-EPMC9917302 | biostudies-literature
Project description:Although prenatal exposure to antiepileptic drugs (AEDs) is known to impart relatively higher risks of major congenital malformations, prospective studies have provided refined data that allow us to differentiate the risks of different types and doses of AEDs. As the number of AED prescriptions has dramatically increased in reproductive-aged women with a variety of neuropsychiatric indications, the evolving concepts learned from studies in women with epilepsy can be applied to a much larger group of pregnant women to improve child outcomes while maintaining maternal disease control. In addition to careful selection of the type of medication, the amount of fetal exposure at conception and in the first trimester probably matters across all AEDs. Some AED polytherapy regimens are not associated with a higher risk of malformations, although other outcomes have not yet been formally studied. The individual woman's drug target concentration should be established preconception and maintained during pregnancy, to prevent seizure worsening. Substantial pharmacokinetic changes occur with many of the medications during pregnancy and postpartum, and interindividual variability supports the use of therapeutic drug monitoring for most AEDs. During pregnancy, vigilance and close monitoring should also include intrauterine fetal growth, obstetric complications, and neonatal complications. Breastfeeding can provide additional neurodevelopmental benefit and should be an option for women on AEDs. Knowledge of these key principles enhances our ability to make treatment recommendations with resultant improved maternal and child outcomes. Additional prospective studies are needed to further define the risk-benefit ratio across a variety of medications, dosing strategies, and neuropsychiatric disorders.
| S-EPMC5081129 | biostudies-literature
Project description:ObjectivesThe purpose of this study was to determine how closely generic modified-release antiepileptic drugs (MR-AEDs) resemble reference (brand) formulations by comparing peak concentrations (Cmax), total absorption (area under the curve [AUC]), time to Cmax (Tmax), intersubject variability, and food effects between generic and reference products.MethodsWe tabulated Cmax and AUC data from the bioequivalence (BE) studies used to support the approvals of generic Food and Drug Administration-approved MR-AEDs. We compared differences in 90% confidence intervals of the generic/reference AUC and Cmax geometric mean ratios, and intersubject variability, Tmax and delivery profiles and food effects.ResultsForty-two MR-AED formulations were studied in 3,175 healthy participants without epilepsy in 97 BE studies. BE ratios for AUC and Cmax were similar between most generic and reference products: AUC ratios varied by >15% in 11.4% of BE studies; Cmax varied by >15% in 25.8% of studies. Tmax was more variable, with >30% difference in 13 studies (usually delayed in the fed compared to fasting BE studies). Generic and reference MR products had similar intersubject variability. Immediate-release AEDs showed less intersubject variability in AUC than did MR-AEDs.ConclusionsMost generic and reference MR-AEDs have similar AUC and Cmax values. Ratios for some products, however, are near acceptance limits and Tmax values may vary. Food effects are common with MR-AED products. High variability in pharmacokinetic values for once-a-day MR-AEDs suggests their major advantage compared to immediate-release AED formulations may be the convenience of less frequent dosing to improve adherence.
| S-EPMC4844239 | biostudies-literature