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Frontiers in Neurology 2023We evaluate the effect of distinct clinical features on anti-seizure medication (ASM) doses in seizure-free and not seizure-free patients aged ≥16 years with new-onset...
OBJECTIVE
We evaluate the effect of distinct clinical features on anti-seizure medication (ASM) doses in seizure-free and not seizure-free patients aged ≥16 years with new-onset epilepsy.
MATERIALS AND METHODS
This study included 459 patients with a validated diagnosis of epilepsy. The most prescribed ASMs were oxcarbazepine (OXC; = 307), followed by valproic acid (VPA; = 115), carbamazepine (CBZ; = 81), and lamotrigine (LTG; = 67). The seizure freedom rate with their first or subsequent ASM was 88.0%. A retrospective analysis of patient records was performed to determine any association between doses of ASMs and patient characteristics.
RESULTS
The median OXC dose in seizure-free patients aged >60 years was 600 mg compared to 900 mg in younger patients. When controlling for age but not in an unadjusted model, the median dose of OXC was lower (300 mg, = 0.018) for seizure-free patients compared to non-seizure-free patients, and the median dose of OXC was also 300 mg lower among older patients aged >60 years ( < 0.001). The median OXC doses for men aged ≤60 years were 300 mg higher than for women aged >60 years (900 mg vs. 600 mg, = 0.021). The median dose of VPA was 400 mg higher in men than in women ( < 0.001) and 400 mg higher in not seizure-free patients compared to seizure-free patients only when adjusting for sex ( < 0.001). Higher median doses for CBZ were registered with FAS compared with FBTCS (difference in median doses of 200 mg; = 0.017).
CONCLUSION
Significant OXC dose differences were detected between age groups, whereas VPA dosing was different in men and women. Moreover, CBZ doses were dependent on some seizure types. These data allow for the individualization of the initial target dosing based on key clinical characteristics.
PubMed: 37609660
DOI: 10.3389/fneur.2023.1159339 -
Pharmaceuticals (Basel, Switzerland) Jun 2023Despite receiving appropriate antiseizure medications (ASMs), a relevant percentage of neuropsychiatric patients do not benefit from this approach, and one reason is...
Despite receiving appropriate antiseizure medications (ASMs), a relevant percentage of neuropsychiatric patients do not benefit from this approach, and one reason is subtherapeutic ASMs plasma concentration (C(p)) due to improper drug adherence, interindividual pharmacokinetic differences, or metabolic interactions among different drugs. For these reasons, therapeutic drug monitoring (TDM) by measuring ASMs C(p) is an effective tool that improves pharmacological therapies in clinical practice. Based on these premises, in the present real-world study, we analyzed the C(p) of the most used ASMs in diverse medical conditions, which were assayed during the years 2018-2022 at the University Hospital of Pisa, including about 24,000 samples. This population was largely heterogeneous, and our database did not contain clinical information about the patients. The most used ASMs were Valproate (VPA: 54.5%) and Levetiracetam (LEV: 18.6%), followed by Oxcarbazepine (OxCBZ: 8.3%) and Carbamazepine (CBZ: 7.2%), whereas the associations LEV/VPA, Ethosuximide (ESM)/VPA, and CBZ/VPA were the most frequently proposed. In about 2/3 of assays, ASMs C(p) was in range, except for VPA, which was underdosed in almost half of the samples. Importantly, toxic levels of ASMs C(p) were found very rarely. For VPA, there was a decrease of mean C(p) across ages, from adolescents to older patients, while the C(p) of LEV, CBZ, OxCBZ, and Topiramate (TPM) showed a slight tendency to increase. When we compared females and males, we found that for VPA, the average age was higher for females, whereas women taking Lamotrigine (LTG) and OxCBZ were younger than men. Then, comparing ASMs used in neurologic and psychiatric disorders, based on the request form, it emerged that the mean C(p) of CBZ, OxCBZ, and LTG on samples collected in the Psychiatric Unit was lower compared to the Neurology and Child Neuropsychiatry Units. Finally, the ASMs subjected to multiple dosing starting from an initial subtherapeutic C(p) increased their level at different time points within a year, reaching the reference range for some of them. In conclusion, the present study suggests that TDM is widely applied to monitor ASMs C(p), finding many of them within the reference range, as a demonstration of its utility in clinical practice.
PubMed: 37513857
DOI: 10.3390/ph16070945 -
Journal of Personalized Medicine Jul 2023Despite the high prevalence of epilepsy in individuals with autism spectrum disorder (ASD), there is little information regarding whether seizure characteristics and...
Despite the high prevalence of epilepsy in individuals with autism spectrum disorder (ASD), there is little information regarding whether seizure characteristics and treatment effectiveness change across age. Using an online survey, seizure characteristics, effectiveness of antiepileptic treatments, comorbidities, potential etiologies, and ASD diagnosis were collected from individuals with ASD and seizures. We previously reported overall general patterns of treatment effectiveness but did not examine the effect of seizure characteristics or age on antiepileptic treatment effectiveness. Such information would improve the personalized medicine approach to the treatment of seizures in ASD. Survey data from 570 individuals with ASD and clinical seizures were analyzed. Seizure severity (seizure/week) decreased with age of onset of seizures, plateauing in adolescence, with a greater reduction in generalized tonic-clonic (GTC) seizures with age. Seizure severity was worse in those with genetic disorders, neurodevelopmental regression (NDR) and poor sleep maintenance. Carbamazepine and oxcarbazepine were reported to be more effective when seizures started in later childhood, while surgery and the Atkins/modified Atkins Diet (A/MAD) were reported to be more effective when seizures started early in life. A/MAD and the ketogenic diet were reported to be more effective in those with NDR. Interestingly, atypical Landau-Kleffner syndrome was associated with mitochondrial dysfunction and NDR, suggesting a novel syndrome. These interesting findings need to be verified in independent, prospectively collected cohorts, but nonetheless, these data provide insights into novel relationships that may assist in a better understanding of epilepsy in ASD and provide insight into personalizing epilepsy care in ASD.
PubMed: 37511780
DOI: 10.3390/jpm13071167 -
Molecular Biology Reports Sep 2023Antiepileptic drugs are versatile drugs with the potential to be used in functional drug formulations with drug repurposing approaches. In the present review, we... (Review)
Review
Antiepileptic drugs are versatile drugs with the potential to be used in functional drug formulations with drug repurposing approaches. In the present review, we investigated the anticancer properties of antiepileptic drugs and interlinked cancer and epileptic pathways. Our focus was primarily on those drugs that have entered clinical trials with positive results and those that provided good results in preclinical studies. Many contributing factors make cancer therapy fail, like drug resistance, tumor heterogeneity, and cost; exploring all alternatives for efficient treatment is important. It is crucial to find new drug targets to find out new antitumor molecules from the already clinically validated and approved drugs utilizing drug repurposing methods. The advancements in genomics, proteomics, and other computational approaches speed up drug repurposing. This review summarizes the potential of antiepileptic drugs in different cancers and tumor progression in the brain. Valproic acid, oxcarbazepine, lacosamide, lamotrigine, and levetiracetam are the drugs that showed potential beneficial outcomes against different cancers. Antiepileptic drugs might be a good option for adjuvant cancer therapy, but there is a need to investigate further their efficacy in cancer therapy clinical trials.
Topics: Neoplasms; Humans; Anticonvulsants; Drug Resistance, Neoplasm; Cell Proliferation; Signal Transduction; Animals
PubMed: 37418080
DOI: 10.1007/s11033-023-08568-1 -
Medicines (Basel, Switzerland) Jun 2023Adverse effects of antiseizure medications (ASMs) remain one of the major causes of non-adherence. Cosmetic side effects (CSEs) are among the most commonly reported... (Review)
Review
Adverse effects of antiseizure medications (ASMs) remain one of the major causes of non-adherence. Cosmetic side effects (CSEs) are among the most commonly reported side effects of ASMs. In this context, alopecia is one of the CSEs that has a high intolerance rate leading to poor therapeutical compliance. We performed a literature review concerning alopecia as a secondary effect of ASMs. There are 1656 individuals reported with ASM-induced alopecia. Valproate (983), lamotrigine (355), and carbamazepine (225) have been extensively reported. Other ASMs associated with alopecia were cenobamate (18), levetiracetam (14), topiramate (13), lacosamide (7), vigabatrin (6), phenobarbital (5), gabapentin (5), phenytoin (4), pregabalin (4), eslicarbazepine (3), brivaracetam (2), clobazam (2), perampanel (2), trimethadione (2), rufinamide (2), zonisamide (2), primidone (1), and tiagabine (1). There were no reports of oxcarbazepine and felbamate with drug-induced alopecia. Hair loss seen with ASMs was diffuse and non-scarring. Telogen effluvium was the most common cause of alopecia. A characteristic feature was the reversibility of alopecia after ASM dose adjustment. Alopecia should be considered one important adverse effect of ASMs. Patients reporting hair loss with ASM therapy should be further investigated, and specialist consultation is recommended.
PubMed: 37367730
DOI: 10.3390/medicines10060035 -
Pharmaceutical Research Jul 2023Oxcarbazepine (OXC) is a frequently prescribed antiepileptic drug for managing focal and generalized seizures. Its therapeutic benefits are limited by its dose-dependent...
BACKGROUND
Oxcarbazepine (OXC) is a frequently prescribed antiepileptic drug for managing focal and generalized seizures. Its therapeutic benefits are limited by its dose-dependent side effects. Nose-to-brain delivery is a novel route for improving the efficacy of antiepileptics. Drug encapsulation in mucoadhesive nanoparticles offers even more advantages for the nasal route.
OBJECTIVE
The study aimed to develop oxcarbazepine-loaded chitosan nanoparticles (OXC-NP) added to a mucoadhesive thermo-reversible gel for intranasal delivery and enhancement of antiepileptic activity.
METHODS
The formulation was optimized based on entrapment efficiency, polydispersity index, particle size, zeta potential, and in vitro release analysis. The therapeutic efficacy of OXC-NP was assessed in an epileptic rat model and compared to intranasal OXC and oral OXC.
RESULTS
The optimized OXC-NPs with chitosan exhibited particle size, zeta potential, and entrapment efficiency of 189 nm, + 31.4 mV ± 2.5 and 97.6% ± 0.14, respectively. The release of OXC was prolonged, reaching 47.1% after 6 h and 55% after 24 h. Enhanced antiepileptic activity of OXC-NP was manifested as decreased seizure score and prolonged survival. Halting of hippocampal TNF-α and IL-6 together with upregulated IL-10 could explain its anti-inflammatory mechanisms.
CONCLUSIONS
Intranasal OXC-NP-loaded in situ gel represents a promising formulation for enhanced antiepileptic potential achieved at low drug concentrations.
Topics: Rats; Animals; Anticonvulsants; Oxcarbazepine; Chitosan; Brain; Administration, Intranasal; Nanoparticles; Particle Size; Drug Carriers
PubMed: 37353628
DOI: 10.1007/s11095-023-03552-7 -
Cureus May 2023Currently, we have a shortage of comprehensive information about newer antiepileptic drugs (AEDs) in the pediatric population. This might explain the discrepancies among...
BACKGROUND AND OBJECTIVES
Currently, we have a shortage of comprehensive information about newer antiepileptic drugs (AEDs) in the pediatric population. This might explain the discrepancies among pediatricians' preferences in this regard. Therefore, it is crucial to study the multifaceted impacts of these drugs on children. The endpoints of our study were non-AED predictors of the requirement of combination therapy for seizure management, seizure-free period >6 months and >12 months, change in Quality of Life in Childhood Epilepsy Questionnaire - 55 (QOLCE-55), and incidence of adverse events.
METHODS
This prospective, observational study was conducted in KIMS, Bhubaneswar, India, from January 2021 to November 2022. Children of 2-12 years of age were treated with monotherapy of either newer antiepileptics, e.g., levetiracetam, topiramate, and oxcarbazepine or older antiepileptics, e.g., valproic acid, phenytoin, phenobarbital, and carbamazepine. Univariate and multivariate analyses were performed for the assessment of predictors. We used R software (version 4.1.1) for data analysis.
RESULTS
One hundred and ninety-eight (91.7%) of 216 enrolled participants completed this study. The mean age of the study population was 5.2 years and 117 (59%) of them were males. The univariate analysis showed that male gender, low birth weight, preterm birth, assisted vaginal delivery and site-specific epilepsy, and maternal history of epilepsy were significant predictors of combination therapy and reduced seizure-free period. There was a non-significant difference regarding the improvement of QOLCE-55 scores. None of the adverse events were serious.
CONCLUSIONS
Perinatal complications and maternal history of epilepsy contribute significantly toward the efficacy of antiepileptics. However, multivariate analysis did not yield statistically significant results.
PubMed: 37332450
DOI: 10.7759/cureus.39173 -
Supportive Care in Cancer : Official... Jun 2023The purpose of this retrospective cohort study was to evaluate whether several potentially preventive therapies reduced the rate of oxaliplatin-induced peripheral...
PURPOSE
The purpose of this retrospective cohort study was to evaluate whether several potentially preventive therapies reduced the rate of oxaliplatin-induced peripheral neuropathy (OIPN) in colorectal cancer patients and to assess the relationship of sociodemographic/clinical factors with OIPN diagnosis.
METHODS
Data were obtained from the Surveillance, Epidemiology, and End Results database combined with Medicare claims. Eligible patients were diagnosed with colorectal cancer between 2007 and 2015, ≥ 66 years of age, and treated with oxaliplatin. Two definitions were used to denote diagnosis of OIPN based on diagnosis codes: OIPN 1 (specific definition, drug-induced polyneuropathy) and OIPN 2 (broader definition, additional codes for peripheral neuropathy). Cox regression was used to obtain hazard ratios (HR) with 95% confidence intervals (CI) for the relative rate of OIPN within 2 years of oxaliplatin initiation.
RESULTS
There were 4792 subjects available for analysis. At 2 years, the unadjusted cumulative incidence of OIPN 1 was 13.1% and 27.1% for OIPN 2. For both outcomes, no therapies reduced the rate of OIPN diagnosis. The anticonvulsants gabapentin and oxcarbazepine/carbamazepine were associated with an increased rate of OIPN (both definitions) as were increasing cycles of oxaliplatin. Compared to younger patients, those 75-84 years of age experienced a 15% decreased rate of OIPN. For OIPN 2, prior peripheral neuropathy and moderate/severe liver disease were also associated with an increased hazard rate. For OIPN 1, state buy-in health insurance coverage was associated with a decreased hazard rate.
CONCLUSION
Additional studies are needed to identify preventive therapeutics for OIPN in cancer patients treated with oxaliplatin.
Topics: United States; Humans; Aged; Oxaliplatin; Antineoplastic Agents; Retrospective Studies; Organoplatinum Compounds; Medicare; Peripheral Nervous System Diseases; Colorectal Neoplasms
PubMed: 37294347
DOI: 10.1007/s00520-023-07850-z -
Indian Pediatrics Jun 2023A prospective longitudinal study was conducted to assess the Apo B100/A1 ratio as a marker of cardiovascular risk in children with epilepsy aged 5-14 years on long-term...
A prospective longitudinal study was conducted to assess the Apo B100/A1 ratio as a marker of cardiovascular risk in children with epilepsy aged 5-14 years on long-term anti-seizure medication monotherapy with either sodium valproate, oxcarbazepine, or levetiracetam. Apo B100/A1 ratio showed an increase after six months of monotherapy with oxcarbazepine (P=0.05).
Topics: Child; Humans; Oxcarbazepine; Levetiracetam; Valproic Acid; Anticonvulsants; Longitudinal Studies; Prospective Studies; Carbamazepine; Epilepsy
PubMed: 37293912
DOI: No ID Found -
Frontiers in Psychiatry 2023Patients treated with anticonvulsant mood stabilizers have a higher incidence of polycystic ovary syndrome (PCOS). However, there is no comparison between different...
Comparison of the probability of four anticonvulsant mood stabilizers to facilitate polycystic ovary syndrome in women with epilepsies or bipolar disorder-A systematic review and meta-analysis.
BACKGROUND
Patients treated with anticonvulsant mood stabilizers have a higher incidence of polycystic ovary syndrome (PCOS). However, there is no comparison between different anticonvulsant mood stabilizers. The purpose of this study was to systematically evaluate the prevalence of PCOS in women taking anticonvulsant mood stabilizers and compare the probability of PCOS caused by different anticonvulsant mood stabilizers.
METHODS
Five databases, namely PubMed, Embase, Web of Science, Cochrane Library, and Clinical Trials, were searched for literature on anticonvulsant mood stabilizers and PCOS published up to October 28, 2022. This meta-analysis was performed using Revman 5.4, Stata 14.0, and R4.1.0, and effect size pooling was performed in fixed- or random-effects models based on the results of and Q-test, and the surface under the cumulative ranking curve (SUCRA) was used for analysis to assess the cumulative probability of drug-induced PCOS. Publication bias was assessed by funnel plot Egger's test and meta regression.
RESULTS
Twenty studies with a total of 1,524 patients were included in a single-arm analysis, which showed a combined effect size (95% CI) of 0.21 (0.15-0.28) for PCOS in patients taking anticonvulsant mood stabilizers. Nine controlled studies, including 500 patients taking medication and 457 healthy controls, were included in a meta-analysis, which showed OR = 3.23 and 95% CI = 2.19-4.76 for PCOS in women taking anticonvulsant mood stabilizers. Sixteen studies with a total of 1416 patients were included in a network meta-analysis involving four drugs, valproate (VPA), carbamazepine (CBZ), oxcarbazepine (OXC), and lamotrigine (LTG), and the results of the network meta-analysis showed that VPA (OR = 6.86, 95% CI = 2.92-24.07), CBZ (OR = 3.28, 95% CI = 0.99-12.64), OXC (OR = 4.30, 95% CI = 0.40-49.49), and LTG (OR = 1.99, 95% CI = 0.16-10.30), with cumulative probabilities ranked as VPA (90.1%), OXC (63.9%), CBZ (50.1%), and LTG (44.0%).
CONCLUSION
The incidence of PCOS was higher in female patients treated with anticonvulsant mood stabilizers than in the healthy population, with VPA having the highest likelihood of causing PCOS. The most recommended medication when considering PCOS factors is LTG.
SYSTEMATIC REVIEW REGISTRATION
identifier: CRD42022380927.
PubMed: 37229383
DOI: 10.3389/fpsyt.2023.1128011