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American Journal of Translational... 2024To explore the effect of levetiracetam combined with oxcarbazepine on the memory and cognitive function of adult patients with temporal lobe epilepsy.
OBJECTIVE
To explore the effect of levetiracetam combined with oxcarbazepine on the memory and cognitive function of adult patients with temporal lobe epilepsy.
METHODS
This retrospective analysis included 91 adult patients with temporal lobe epilepsy treated at Xianyang Hospital from June 2020 to December 2022. Based on their medication regimen, patients were categorized into an observation group (n=51) receiving levetiracetam plus oxcarbazepine and a control group (n=40) receiving only levetiracetam. Both groups underwent 3 months of continuous treatment. Therapeutic efficacy, pre- and post-treatment memory function (assessed using the Clinical Memory Scale, CMS), cognitive function (evaluated with the Wechsler Adult Intelligence Scale-Revised in China, WAISRC), anxiety and depression levels (measured by the Hamilton Anxiety Scale, HAMA, and Hamilton Depression Scale, HAMD), as well as adverse reactions, were compared between the two groups. Independent factors influencing treatment efficacy were also analyzed.
RESULTS
CMS and WAISRC scores significantly increased in both groups after treatment (both P=0.001), with the observation group showing more significant improvements than the control group (P=0.001). The improvements in HAMA and HAMD scores in the observation group were significantly better than the control group (all P<0.001). Adverse reaction occurrence showed no significant difference between the two groups (P>0.05). Prognostic analysis identified seizure frequency and treatment regimen as independent factors influencing efficacy.
CONCLUSION
Levetiracetam combined with oxcarbazepine effectively improves cognitive dysfunction in adults with temporal lobe epilepsy, with superior efficacy to levetiracetam alone, and good safety.
PubMed: 38586112
DOI: 10.62347/KNTE8578 -
Journal of Pharmacy Practice Jun 2024Phenytoin (PHT) has been approved for the treatment of epilepsy. It belongs to the category of medications with a limited therapeutic window and requires therapeutic...
Phenytoin (PHT) has been approved for the treatment of epilepsy. It belongs to the category of medications with a limited therapeutic window and requires therapeutic drug monitoring (TDM). PTH has been observed to induce a variety of Adverse drug reactions (ADRs) including ataxia, dystonia, nystagmus, dyskinesia, etc. Phenytoin-induced ataxia is an uncommonly observed ADR of Phenytoin whose reports are extremely limited. Herein, we present a case report of a 16-year-old Asian patient with a past history of epilepsy that was admitted to a tertiary care hospital due to the development of ataxia, giddiness, and vomiting when taking Phenytoin in addition to Oxcarbazepine, Clobazam, and Levetiracetam to treat seizures. On admission, Magnetic resonance imaging (MRI) findings revealed bilateral variable cerebrospinal fluid (CSF) lesions in the parieto-occipital region of the periventricular area (periventricular leukomalacia). Additionally, serum Phenytoin levels were observed to be in the toxic range (40 μg/mL) due to which physicians confirmed the ADR to be due to Phenytoin toxicity. Thus, the Phenytoin drug was discontinued in the patient gradually and he was continued on clobazam, oxcarbazepine, and brivaracetam which led to reversal of the ADR in the patient. In this case, ataxia resulted from Phenytoin overdose, as confirmed by MRI and serum tests suggesting that TDM of Phenytoin is essential to prevent ADRs. Given the scarcity of ataxia cases caused by Phenytoin, awareness is lacking within the scientific community. Our aim is to provide insights to promote better monitoring and patient-centered treatment outcomes for epileptic patients.
PubMed: 38871356
DOI: 10.1177/08971900241262379 -
JAMA Network Open Feb 2024Use of valproate and certain other antiseizure medications (ASMs) in pregnancy is associated with abnormal fetal brain development with potential long-term implications...
IMPORTANCE
Use of valproate and certain other antiseizure medications (ASMs) in pregnancy is associated with abnormal fetal brain development with potential long-term implications for the child.
OBJECTIVE
To examine whether use of valproate and other ASMs in pregnancy among mothers with epilepsy is associated with epilepsy risk in their children.
DESIGN, SETTING, AND PARTICIPANTS
This prospective, population-based register cohort study included singletons born to mothers with epilepsy in Denmark, Finland, Iceland, Norway, and Sweden from January 1, 1996, to December 31, 2017. Data analysis was performed from October 2022 to December 2023.
EXPOSURE
Redeemed prescription for an ASM from 30 days before pregnancy until birth.
MAIN OUTCOMES AND MEASURES
The main outcome was epilepsy in children, assessed using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses from hospital care. Adjusted hazard ratios (AHRs) and 95% CIs were estimated using Cox proportional hazards regression. Secondary analyses included dose-response analyses, analyses using children of mothers who discontinued ASM prior to pregnancy as the reference, and sibling analyses.
RESULTS
This cohort study included 38 663 children of mothers with epilepsy (19 854 [51.4%] boys). Children were followed up from birth; the mean length of follow-up was 7.2 years (range 0-22 years). Compared with 22 207 children of mothers not using an ASM in pregnancy, increased risks of epilepsy in children of mothers who used valproate in pregnancy (monotherapy: AHR, 2.18; 95% CI, 1.70-2.79; polytherapy: AHR, 2.10; 95% CI, 1.49-2.96) were observed. However, there was no dose-dependent association, and there was a similar risk of epilepsy in siblings who were exposed and unexposed to valproate (AHR, 0.95; 95% CI, 0.50-1.82). Prenatal exposure to topiramate monotherapy was associated with increased risk of epilepsy (AHR, 2.32; 95% CI, 1.30-4.16), and the risk was greater for higher doses, but the risk attenuated in comparisons with children of mothers who discontinued topiramate before pregnancy (AHR, 1.19; 95% CI, 0.26-5.44). Prenatal exposure to clonazepam monotherapy was also associated with increased epilepsy risk (AHR, 1.90; 95% CI, 1.16-3.12), but limited follow-up and low numbers precluded further analyses. No associations were observed for prenatal exposure to lamotrigine (AHR, 1.18; 95% CI, 0.95-1.47), levetiracetam (AHR, 1.28; 95% CI, 0.77-2.14), carbamazepine (AHR, 1.13; 95% CI, 0.85-1.50), or oxcarbazepine (AHR, 0.68; 95% CI, 0.44-1.05).
CONCLUSIONS AND RELEVANCE
In this cohort study of children born to mothers with epilepsy, the associations found between prenatal exposure to certain ASMs and the child's risk of epilepsy did not persist in sensitivity analyses, suggesting that maternal ASM use in pregnancy may not increase epilepsy risk in children beyond that associated with the maternal epilepsy itself. These findings are reassuring for women in need of treatment with ASM in pregnancy.
Topics: Male; Child; Pregnancy; Humans; Female; Valproic Acid; Topiramate; Cohort Studies; Prenatal Exposure Delayed Effects; Prospective Studies; Epilepsy; Vitamins; Mothers
PubMed: 38407908
DOI: 10.1001/jamanetworkopen.2023.56425 -
Epilepsia Feb 2024Antiseizure medications (ASMs) are commonly categorized as enzyme-inducers and non-enzyme-inducers based on their propensity to enhance the metabolism of concomitantly... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Antiseizure medications (ASMs) are commonly categorized as enzyme-inducers and non-enzyme-inducers based on their propensity to enhance the metabolism of concomitantly administered drugs. This systematic review and network meta-analysis aimed to rank ASMs as cytochrome P450 3A (CYP3A)-inducers based on a comparative assessment of ASM-induced reduction in the concentrations of sensitive substrate drugs.
METHODS
The protocol was registered with PROSPERO (International Prospective Register of Systematic Reviews; CRD42022335846), and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) standards were followed. We searched MEDLINE, Embase, and Cochrane until March 14, 2023 without an initial date restriction. Data were additionally obtained via the US Food and Drug Administration database. Studies had to be prospective, with ASM monotherapy for ≥5 days. The primary parameter was the magnitude of change in the area under the concentration-time curve of CYP3A substrates following treatment with the ASM. The standardized mean difference (SMD) was used as the point estimate for the indirect comparisons between ASMs using the pairwise method. Bias risk was assessed using the PKclin tool.
RESULTS
We identified 14 open-label, fixed-sequence studies with 370 participants. The effect size of 600 mg/day carbamazepine did not differ from those of 300 mg/day phenytoin (SMD = -.06, 95% confidence interval [CI] = -.18 to .07) and 200 mg/day cenobamate (SMD = -.11, 95% CI = -.26 to .04). Carbamazepine at 600 mg/day was the strongest CYP3A-inducer (P-score = .88), followed by carbamazepine 400 mg/day (.83), phenytoin 300 mg/day (.79), and cenobamate 200 mg/day (.73). Eslicarbazepine (800 mg/day) ranked higher than cenobamate 100 mg/day and oxcarbazepine 900 mg/day (.60, .39, and .37, respectively).
SIGNIFICANCE
Despite the limited number of studies, our network meta-analysis emphasizes that the magnitude of ASM effects on CYP3A substrate metabolism is a dose-dependent continuum. When possible, ASM classification as inducers should apply cutoff values tailored to the outcome. Prescribers should monitor plasma concentrations or clinical effects of CYP3A substrates and consider selecting concomitant medications accordingly.
Topics: Humans; Cytochrome P-450 CYP3A; Phenytoin; Network Meta-Analysis; Pharmaceutical Preparations; Carbamazepine; Benzodiazepines; Carbamates; Chlorophenols; Tetrazoles
PubMed: 38010146
DOI: 10.1111/epi.17822 -
Children (Basel, Switzerland) Nov 2023Epilepsy is a chronic neurological disease characterized by the presence of spontaneous seizures, with a higher incidence in the pediatric population. Anti-seizure...
Epilepsy is a chronic neurological disease characterized by the presence of spontaneous seizures, with a higher incidence in the pediatric population. Anti-seizure medication (ASM) may produce adverse drug reactions (ADRs) with an elevated frequency and a high severity. Thus, the objective of the present study was to analyze, through intensive pharmacovigilance over 112 months, the ADRs produced by valproic acid (VPA), oxcarbazepine (OXC), phenytoin (PHT), and levetiracetam (LEV), among others, administered to monotherapy or polytherapy for Mexican hospitalized pediatric epilepsy patients. A total of 1034 patients were interviewed; 315 met the inclusion criteria, 211 patients presented ADRs, and 104 did not. A total of 548 ASM-ADRs were identified, and VPA, LEV, and PHT were the main culprit drugs. The most frequent ADRs were drowsiness, irritability, and thrombocytopenia, and the main systems affected were hematologic, nervous, and dermatologic. LEV and OXC caused more nonsevere ADRs, and PHT caused more severe ADRs. The risk analysis showed an association between belonging to the younger groups and polytherapy with ADR presence and between polytherapy and malnutrition with severe ADRs. In addition, most of the severe ADRs were preventable, and most of the nonsevere ADRs were nonpreventable.
PubMed: 38002866
DOI: 10.3390/children10111775 -
CNS Drugs May 2024Post-stroke epilepsy represents an important clinical challenge as it often requires both treatment with direct oral anticoagulants (DOACs) and antiseizure medications... (Comparative Study)
Comparative Study Observational Study
BACKGROUND AND OBJECTIVE
Post-stroke epilepsy represents an important clinical challenge as it often requires both treatment with direct oral anticoagulants (DOACs) and antiseizure medications (ASMs). Levetiracetam (LEV), an ASM not known to induce metabolizing enzymes, has been suggested as a safer alternative to enzyme-inducing (EI)-ASMs in patients treated with DOACs; however, current clinical guidelines suggest caution when LEV is used with DOACs because of possible P-glycoprotein induction and competition (based on preclinical studies). We investigated whether LEV affects apixaban and rivaroxaban concentrations compared with two control groups: (a) patients treated with EI-ASMs and (b) patients not treated with any ASM.
METHODS
In this retrospective observational study, we monitored apixaban and rivaroxaban peak plasma concentrations (C) in 203 patients treated with LEV (n = 28) and with EI-ASM (n = 33), and in patients not treated with any ASM (n = 142). Enzyme-inducing ASMs included carbamazepine, phenytoin, phenobarbital, primidone, and oxcarbazepine. We collected clinical and laboratory data for analysis, and DOAC C of patients taking LEV were compared with the other two groups.
RESULTS
In 203 patients, 55% were female and the mean age was 78 ± 0.8 years. One hundred and eighty-six patients received apixaban and 17 patients received rivaroxaban. The proportion of patients with DOAC C below their therapeutic range was 7.1% in the LEV group, 10.6% in the non-ASM group, and 36.4% in the EI-ASM group (p < 0.001). The odds of having DOAC C below the therapeutic range (compared with control groups) was not significantly different in patients taking LEV (adjusted odds ratio 0.70, 95% confidence interval 0.19-2.67, p = 0.61), but it was 12.7-fold higher in patients taking EI-ASM (p < 0.001). In an analysis in patients treated with apixaban, there was no difference in apixaban C between patients treated with LEV and non-ASM controls, and LEV clinical use was not associated with variability in apixaban C in a multivariate linear regression.
CONCLUSIONS
In this study, we show that unlike EI-ASMs, LEV clinical use was not significantly associated with lower apixaban C and was similar to that in patients not treated with any ASM. Our findings suggest that the combination of LEV with apixaban and rivaroxaban may not be associated with decreased apixaban and rivaroxaban C. Therefore, prospective controlled studies are required to examine the possible non-pharmacokinetic mechanism of the effect of the LEV-apixaban or LEV-rivaroxaban combination on patients' outcomes.
Topics: Aged; Female; Humans; Male; Anticoagulants; Atrial Fibrillation; Dabigatran; Levetiracetam; Prospective Studies; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban
PubMed: 38520503
DOI: 10.1007/s40263-024-01077-0 -
Frontiers in Pharmacology 2023[This corrects the article DOI: 10.3389/fphar.2023.1189058.].
[This corrects the article DOI: 10.3389/fphar.2023.1189058.].
PubMed: 37841932
DOI: 10.3389/fphar.2023.1295784 -
Neurology India 2023Most pregnant epilepsy patients need to continue using anti-seizure medications (ASMs) to control epileptic seizures.
BACKGROUND
Most pregnant epilepsy patients need to continue using anti-seizure medications (ASMs) to control epileptic seizures.
OBJECTIVE
This study aimed to evaluate the risk of early abortion in pregnant epilepsy patients exposed to anti-seizure monotherapy.
METHODS AND MATERIAL
We prospectively followed up pregnant epilepsy patients treated with anti-seizure monotherapy in our epilepsy center between January 2010 and January 2020 under real-world conditions. Early abortion (spontaneous abortion in the first trimester of pregnancy) was the endpoint.
RESULTS
Of 211 pregnancies exposed to monotherapy, including 40% (n = 85) to lamotrigine (LTG), 28% (n = 58) to oxcarbazepine (OXC), 15% (n = 32) to sodium valproate (VPA), 9% (n = 19) to levetiracetam, and 8% (n = 17) to carbamazepine, six ended in early abortion. The overall risk of early abortion in pregnant patients exposed to ASM monotherapy was 2.8% (n = 6) [95% confidence interval (CI) = 0.013-0.073]. The risk of early abortion was 2.4% (n = 2) (95% CI = 0.003-0.082) in women treated with LTG, 3.5% (n = 2) (95% CI = 0.004-0.115) in women treated with OXC, and 6.3% (n = 2) (95% CI = 0.008-0.208) in women treated with VPA. The relative risk of early abortion in the LTG, OXC, and VPA groups did not reach statistical significance.
CONCLUSIONS
Although the sample size of our study was small, these results indicate that the use of anti-seizure monotherapy in pregnant epilepsy patients may not increase the risk of early miscarriage. Larger prospective studies are needed for sufficient statistical analysis.
Topics: Pregnancy; Humans; Female; Anticonvulsants; Epilepsy; Lamotrigine; Oxcarbazepine; Carbamazepine; Valproic Acid
PubMed: 37929429
DOI: 10.4103/0028-3886.388098 -
Annals of the Child Neurology Society Mar 2024Ninety percent of infants with Sturge-Weber syndrome (SWS) brain involvement have seizure onset before 2 years of age; this is associated with worse neurologic outcome....
BACKGROUND
Ninety percent of infants with Sturge-Weber syndrome (SWS) brain involvement have seizure onset before 2 years of age; this is associated with worse neurologic outcome. Presymptomatic treatment before seizure onset may delay seizure onset and improve outcome, as has been shown in other conditions with a high-risk of developing epilepsy such as tuberous sclerosis complex. Electroencephalogram (EEG) may be a biomarker to predict seizure onset. This retrospective clinical data analysis aims to assess impact of presymptomatic treatment in SWS.
METHODS
This two-centered, IRB-approved, retrospective study analyzed records from patients with SWS brain involvement. Clinical data recorded included demographics, age of seizure onset (if present), brain involvement extent (unilateral versus bilateral), port-wine birthmark (PWB) extent, family history of seizure, presymptomatic treatment if received, neuroscore, and anti-seizure medication. EEG reports prior to seizure onset were analyzed.
RESULTS
Ninety-two patients were included (48 females), and 32 received presymptomatic treatment outside of a formal protocol (5 aspirin, 16 aspirin and levetiracetam; 9 aspirin and oxcarbazepine, 2 valproic acid). Presymptomatically-treated patients were more likely to be seizure-free at 2 years (15 of 32; 47% versus 7 of 60; 12%; p<.001). A percentage of presymptomatically-treated patients had bilateral brain involvement (38% treated versus 17% untreated; p=.026). Median hemiparesis neuroscore at 2 years was better in presymptomatically-treated patients. In EEG reports prior to seizure onset, the presence of slowing, epileptiform discharges, or EEG-identified seizures was associated with seizure onset by 2 (p=.001).
CONCLUSION
Presymptomatic treatment is a promising approach to children diagnosed with SWS prior to seizure onset. Further study is needed, including prospective drug trials, long-term neuropsychological outcome, and prospective EEG analysis to assess this approach and determine biomarkers for presymptomatic treatment.
PubMed: 38745912
DOI: 10.1002/cns3.20058 -
Zhonghua Er Ke Za Zhi = Chinese Journal... Nov 2023To analyze the efficacy and safety of the sodium channel blockers (SCB) antiseizure medication in the treatment of focal epilepsy in infants under 6 months of age....
To analyze the efficacy and safety of the sodium channel blockers (SCB) antiseizure medication in the treatment of focal epilepsy in infants under 6 months of age. This was a case series study. Infants with focal epilepsy with onset within 6 months of age and treated with SCB attending the Department of Neurology of Beijing Children's Hospital from June 2016 to April 2022 were collected. The clinical data, auxiliary examinations, SCB application, efficacy, adverse reactions, and prognosis were analyzed retrospectively. Patients were grouped according to type of seizure and epileptic syndrome, age of onset and etiology. Chi square test and Fisher exact test were used to analyze the differences between groups statistically. A total of 118 infants were enrolled, 65 males and 53 females, with an age of epilepsy onset of 56 (4, 114) days. Developmental and epileptic encephalopathy was diagnosed in 60 infants, 39 had self-limited neonatal and (or) infantile epilepsy, and 19 had non-syndromic focal epilepsy. Application of SCB: 106 used oxcarbazepine, 2 used lacosamide, 9 switched from oxcarbazepine to lacosamide or a combination of 2 SCB, and 1 used oxcarbazepine, lacosamide, and lamotrigine successively; oxcarbazepine was the first choice in 46 cases. The age at which SCB was applied was 103 (53, 144) days. The children were followed up for 6 months to 6 years. SCB was effective in 89 cases (75.4%), including 70 cases (59.3%) who achieved seizure freedom. The seizure-free rate was higher in the focal epilepsy only group than in the group with other seizure types (64.4% (65/101) 4/17, ²=9.99, <0.05). The responder and seizure-free rates were all higher in the group with the onset age of >3-6 months than the group >1-3 months (84.4% (38/45) 62.5% (20/32), 73.3% (33/45) 46.9% (15/32), ²=4.85 and 5.58, both <0.05). With the exception of variants in the PRRT2 gene, those with variants in sodium or potassium channels had higher responder and seizure-free rates than those with variants in other genes(86.2% (25/29) 45.5% (10/22), 62.1% (18/29) 22.7% (5/22), ²=9.65 and 7.82,both <0.05). The most common adverse event was transient hyponatremia, which happened in 66 cases (55.9%). There were 9 cases of rash, which subsided in 6 cases after discontinuing oxcarbazepine and switching to lacosamide, and 7 cases of electrocardiogram abnormalities, which improved after withdrawing oxcarbazepine and changing to lacosamide in 1 case. SCB are effective and tolerable in the treatment of focal epilepsy in infants under 6 months of age, with better efficacy in patients with genetic variants of the sodium or potassium channel, focal seizures only, and seizure onset >3-6 months of age.
Topics: Child; Female; Male; Infant, Newborn; Humans; Infant; Sodium Channel Blockers; Oxcarbazepine; Lacosamide; Retrospective Studies; Epilepsies, Partial; Seizures; Sodium; Anticonvulsants
PubMed: 37899337
DOI: 10.3760/cma.j.cn112140-20230731-00057