-
Brain Sciences Jul 2021Carbamazepine and oxcarbazepine are used for behavioral disorders following organic diseases. After severe acquired brain injury, patients may develop frontal symptoms....
Carbamazepine and oxcarbazepine are used for behavioral disorders following organic diseases. After severe acquired brain injury, patients may develop frontal symptoms. In our neurological rehabilitation routine, oxcarbazepine is used for better safety over carbamazepine, although its efficacy is not clarified. We aimed to improve knowledge on this use of oxcarbazepine, by probing clinical factors associated with response. We retrospectively examined the clinical records of our patients, collecting clinical variables and outcomes of efficacy, both clinician-rated and caregiver/self-rated. We described the distribution of clinical variables and examined their associations via logistic regressions. Patients in our cohort were predominantly pediatric, with frontal lobe damage and irritable/reactive. With an oxcarbazepine median dose of 975 mg, almost half of patients improved. We found several clinical factors associated with clinician-rated efficacy: absence of frontal damage and absence of irritability/reactivity symptoms; clinical factors associated with caregivers/patients-rated efficacy were: higher DRS score at baseline and higher patient age. In this retrospective study, we observed that oxcarbazepine was differentially efficacious in patients with specific characteristics. Our study could not examine drug therapy separately from neuropsychological therapy, nor the influence of dose. Our associative results should be verified experimentally, also assessing causality and establishing dose-related efficacy and safety.
PubMed: 34356183
DOI: 10.3390/brainsci11070949 -
The Cochrane Database of Systematic... Mar 2020Epilepsy is a common neurological disorder. In approximately 30% of epilepsy cases, seizures are uncontrolled by one antiepileptic drug (AED). These people require... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epilepsy is a common neurological disorder. In approximately 30% of epilepsy cases, seizures are uncontrolled by one antiepileptic drug (AED). These people require treatment with a combination of multiple AEDs and are described as having drug-resistant epilepsy. Oxcarbazepine is a keto-analogue of carbamazepine, an established AED, and can be used as an add-on treatment for drug-resistant epilepsy.
OBJECTIVES
To assess the efficacy and tolerability of oxcarbazepine as an add-on treatment for people with drug-resistant focal epilepsy.
SEARCH METHODS
The following databases were searched on 24 September 2018: Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL); Medline (Ovid) 1946 to 21 September 2018; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). Originally, we also searched SCOPUS as a substitute for Embase, but this is no longer necessary, because randomised and quasi-randomised controlled trials in Embase are now included in CENTRAL.
SELECTION CRITERIA
Randomised controlled trials with parallel-group or cross-over design, recruiting people of any age with drug-resistant focal epilepsy. We accepted any level of blinding and trials could be placebo- or active-controlled.
DATA COLLECTION AND ANALYSIS
In accordance with the methodological procedures expected by the Cochrane Collaboration, two review authors independently assessed trial eligibility before extracting data and assessing risk of bias. We assessed the primary outcomes: median percentage seizure reduction per 28 days; 50% or greater reduction in seizure frequency; and adverse effects including ataxia, hyponatraemia, and somnolence. We assessed the secondary outcomes: seizure freedom; treatment withdrawal; cognitive effects; and quality of life. We used an intention-to-treat population for all primary analyses. We present results as risk ratios (RR) with 95% confidence intervals (CI), with the exception of adverse effects which we present with 99% CI.
MAIN RESULTS
We identified six eligible studies, involving 1593 participants. We judged that three studies were at unclear risk of bias and three were at high risk of bias. Bias mainly arose from lack of methodological details and from high attrition rates. Participants were aged 1 month to 65 years, with a diagnosis of drug-resistant focal epilepsy. All studies were either placebo- or alternative-dose-controlled with parallel-group design. The treatment period varied from 9 days to 26 weeks. The median percentage seizure reduction per 28 days (3 studies; moderate-certainty evidence) ranged from 26% to 83.3% for participants randomised to experimental oxcarbazepine compared to 7.6% to 28.7% for participants randomised to control treatment. Oxcarbazepine may increase the responder rate for 50% or greater reduction in seizure frequency compared to control treatment (RR 1.80, 95% CI 1.27 to 2.56; random-effects model; 6 studies; low-certainty evidence). For seizure freedom, the RR was 2.86 (95% CI 1.19 to 6.87; random-effects model; 5 studies; low-certainty evidence), suggesting an advantageous effectiveness of oxcarbazepine over control treatment. Treatment with oxcarbazepine was associated with an increased treatment withdrawal rate compared to control (RR 1.75, 95% CI 1.44 to 2.13; fixed-effect model; 6 studies; moderate-certainty evidence). The largest oxcarbazepine dose used, 2400 mg/d, was associated with a higher treatment withdrawal rate (RR 2.38, 95% CI 1.92 to 2.94; fixed-effect model; 2 studies) compared to control, than 1200 mg/d (RR 1.54, 95% CI 1.21 to 1.95; fixed-effect model; 3 studies) or 600 mg/d oxcarbazepine (RR 0.79, 95% CI 0.55 to 1.15; fixed-effect model; 1 study). Treatment with oxcarbazepine was associated with an increased incidence of multiple adverse effects including: ataxia (RR 2.54, 99% CI 0.86 to 7.54; random-effects model; 5 studies; moderate-certainty evidence); and somnolence (RR 2.03, 99% CI 1.17 to 3.54; random-effects model; 6 studies; low-certainty evidence). Hyponatraemia occurred more frequently with oxcarbazepine treatment but not significantly so (RR 2.53, 99% CI 0.27 to 23.85; fixed-effect model; 6 studies; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Oxcarbazepine might be effective at reducing seizure frequency when used as an add-on for drug-resistant focal epilepsy. The efficacy outcomes - 50% or greater seizure reduction and seizure freedom - were derived from low-certainty evidence. We are, therefore, uncertain whether the estimated effect size is representative of the true effect. In contrast, the evidence for median percentage seizure reduction and treatment withdrawal were of moderate certainty: thus, we are fairly certain of the effect estimates' reliability. Overall, we are unsure of the true efficacy of oxcarbazepine, but have concerns about its tolerability.
Topics: Anticonvulsants; Drug Resistant Epilepsy; Drug Therapy, Combination; Humans; Intention to Treat Analysis; Oxcarbazepine; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32129501
DOI: 10.1002/14651858.CD012433.pub2 -
Epilepsia Jan 2013To evaluate the pharmacokinetics and tolerability of once-daily eslicarbazepine acetate (ESL) and twice-daily oxcarbazepine (OXC) and their metabolites in cerebrospinal... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate the pharmacokinetics and tolerability of once-daily eslicarbazepine acetate (ESL) and twice-daily oxcarbazepine (OXC) and their metabolites in cerebrospinal fluid (CSF) and plasma following repeated oral administration.
METHODS
Single-center, open-label, randomized, parallel-group study in healthy volunteers. Volunteers in ESL group (n = 7) received 600 mg on days 1-3 and 1,200 mg on days 4-9, once daily. Volunteers in the OXC group (n = 7) received 300 mg on days 1-3 and 600 mg on days 4-9, twice daily. Plasma and CSF sampling was performed following the last dose.
KEY FINDINGS
Eslicarbazepine was the major drug entity in plasma and CSF, accounting for, respectively, 93.84% and 91.96% of total exposure in the ESL group and 78.06% and 76.42% in the OXC group. The extent of exposure to drug entities R-licarbazepine and oxcarbazepine was approximately four-fold higher with OXC as compared with ESL. There was relatively little fluctuation from peak-to-trough (ratio) in the CSF for both eslicarbazepine (ESL = 1.5; OXC = 1.2) and R-licarbazepine (ESL = 1.2; OXC = 1.2). In contrast, oxcarbazepine showed larger differences between peak and trough (ESL = 3.1; OXC = 6.4). A total of 84 and 24 treatment-emergent adverse events (TEAEs) were reported with OXC and ESL, respectively.
SIGNIFICANCE
In comparison to OXC, administration of ESL resulted in more eslicarbazepine, less R-licarbazepine, and less oxcarbazepine in plasma and CSF, which may correlate with the tolerability profile reported with ESL. The smaller peak-to-trough fluctuation of eslicarbazepine in CSF (a measure of sustained delivery to the brain) than in plasma supports once-daily dosing of ESL.
Topics: Administration, Oral; Adult; Anticonvulsants; Carbamazepine; Dibenzazepines; Female; Humans; Male; Middle Aged
PubMed: 22812691
DOI: 10.1111/j.1528-1167.2012.03595.x -
CNS Drugs Apr 2013Partial-onset seizures contribute the bulk of seizure burden in childhood epilepsy. The therapeutic decision making involves consideration of factors specific to drug,... (Review)
Review
BACKGROUND
Partial-onset seizures contribute the bulk of seizure burden in childhood epilepsy. The therapeutic decision making involves consideration of factors specific to drug, patient and socioeconomic situation.
OBJECTIVES
This paper systematically reviews the available efficacy/effectiveness evidence for various anti-epileptic drugs (AED) as monotherapy and adjunctive therapy for partial-onset seizures in children.
DATA SOURCES
Relevant randomized clinical trials (RCTs) were identified by a structured PubMed search, supplemented by an additional hand search of reference lists and authors' files.
STUDY APPRAISAL AND SYNTHESIS METHODS
Eligible studies were reviewed and data extracted into tables. Included RCTs were classified based on accepted published criteria.
OUTCOMES
Only efficacy and effectiveness outcome measures were evaluated since there is little scientifically rigorous comprehensive AED adverse effects data.
RESULTS
Oxcarbazepine is the only AED with Class I evidence for efficacy/effectiveness as initial monotherapy for partial-onset seizures in children. Carbamazepine, clobazam, lamotrigine, phenobarbital, phenytoin, topiramate, valproate, vigabatrin and zonisamide have, at best, Class III efficacy/effectiveness evidence for monotherapy of partial-onset seizures in children. For adjunctive therapy, gabapentin, lamotrigine, levetiracetam, oxcarbazepine and topiramate have Class I efficacy/effectiveness evidence for treatment of pediatric partial-onset seizures.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
This efficacy/effectiveness analysis must not be used in isolation when selecting therapy. AED selection for a specific child needs to integrate a drug's efficacy/effectiveness data with its safety and tolerability profile, pharmacokinetic properties, available formulations, and patient specific characteristics. It is critical that physicians and patients incorporate all these relevant variables when choosing AED therapy.
Topics: Anticonvulsants; Child; Decision Making; Drug Approval; Epilepsies, Partial; Humans; Randomized Controlled Trials as Topic; Socioeconomic Factors; Treatment Outcome
PubMed: 23515971
DOI: 10.1007/s40263-013-0048-z -
International Journal of Molecular... Jan 2021Accumulating experimental studies show that antiarrhythmic and antiepileptic drugs share some molecular mechanisms of action and can interact with each other. In this...
Accumulating experimental studies show that antiarrhythmic and antiepileptic drugs share some molecular mechanisms of action and can interact with each other. In this study, the influence of amiodarone (a class III antiarrhythmic drug) on the antiseizure action of four second-generation antiepileptic drugs was evaluated in the maximal electroshock model in mice. Amiodarone, although ineffective in the electroconvulsive threshold test, significantly potentiated the antielectroshock activity of oxcarbazepine and pregabalin. Amiodarone, given alone or in combination with oxcarbazepine, lamotrigine, or topiramate, significantly disturbed long-term memory in the passive-avoidance task in mice. Brain concentrations of antiepileptic drugs were not affected by amiodarone. However, the brain concentration of amiodarone was significantly elevated by oxcarbazepine, topiramate, and pregabalin. Additionally, oxcarbazepine and pregabalin elevated the brain concentration of desethylamiodarone, the main metabolite of amiodarone. In conclusion, potentially beneficial action of amiodarone in epilepsy patients seems to be limited by neurotoxic effects of amiodarone. Although results of this study should still be confirmed in chronic protocols of treatment, special precautions are recommended in clinical conditions. Coadministration of amiodarone, even at low therapeutic doses, with antiepileptic drugs should be carefully monitored to exclude undesired effects related to accumulation of the antiarrhythmic drug and its main metabolite, desethylamiodarone.
Topics: Amiodarone; Animals; Anticonvulsants; Avoidance Learning; Behavior, Animal; Brain; Disease Models, Animal; Electroshock; Epilepsy; Mice; Oxcarbazepine; Pregabalin
PubMed: 33494393
DOI: 10.3390/ijms22031041 -
Neurology Sep 2018To characterize the magnitude and time course of pregnancy-related clearance changes for different antiepileptic drugs (AEDs): levetiracetam, oxcarbazepine, topiramate,... (Observational Study)
Observational Study
OBJECTIVE
To characterize the magnitude and time course of pregnancy-related clearance changes for different antiepileptic drugs (AEDs): levetiracetam, oxcarbazepine, topiramate, phenytoin, and valproate. A secondary aim was to determine if a decreased AED serum concentration was associated with increased seizure frequency.
METHODS
Women with epilepsy were enrolled preconception or early in pregnancy and prospectively followed throughout pregnancy and the first postpartum year with daily diaries of AED doses, adherence, and seizures. Study visits with AED concentration measurements occurred every 1-3 months. AED clearances in each trimester were compared to nonpregnant baseline using a mixed linear regression model, with adjustments for age, race, and hours postdose. In women on monotherapy, 2-sample test was used to compare the ratio to target concentrations (RTC) between women with seizure worsening each trimester and those without.
RESULTS
AED clearances were calculated for levetiracetam (n = 18 pregnancies), oxcarbazepine (n = 4), topiramate (n = 10), valproate (n = 5), and phenytoin (n = 7). Mean maximal clearances were reached for (1) levetiracetam in first trimester (1.71-fold baseline clearance) ( = 0.0001), (2) oxcarbazepine in second trimester (1.63-fold) ( = 0.0001), and (3) topiramate in second trimester (1.39-fold) ( = 0.025). In 15 women on AED monotherapy, increased seizure frequency in the first, second, and all trimesters was associated with a lower RTC ( < 0.05).
CONCLUSION
AED clearance significantly changes by the first trimester for levetiracetam and by the second trimester for oxcarbazepine and topiramate. Lower RTC was associated with seizure worsening. Early therapeutic drug monitoring and dose adjustment may be helpful to avoid increased seizure frequency.
Topics: Adolescent; Adult; Anticonvulsants; Epilepsy; Female; Humans; Postpartum Period; Pregnancy; Pregnancy Complications; Pregnancy Trimesters; Preliminary Data; Prospective Studies; Seizures; Young Adult
PubMed: 30185446
DOI: 10.1212/WNL.0000000000006240 -
Pediatric Neurology Jul 2023Knowledge on antiseizure medication (ASM) use and retention for children with epilepsy is limited, partly because of extensive off-label use of newer drugs with limited...
BACKGROUND
Knowledge on antiseizure medication (ASM) use and retention for children with epilepsy is limited, partly because of extensive off-label use of newer drugs with limited registration. We used prescription data to study prescription patterns on a population-wide scale and compared the proportion of patients remaining on monotherapy of ASMs with and without formal indication for different age groups.
METHODS
A total of 14,681 individuals aged <18 years were included, using cross-referenced Swedish registers from 2007 to 2020. Kaplan-Meier retention rates were calculated for all ASMs. The most common pathways of the first three medications per patient were analyzed.
RESULTS
In children older than one month and up to age one year, monotherapy retention rates were the highest for oxcarbazepine, valproic acid, and carbamazepine. Among children aged one to five years, oxcarbazepine and levetiracetam were among ASMs that do not have a monotherapy indication in Sweden but still had high retention rates. In the age group five to 12 years, lamotrigine and oxcarbazepine had the highest retention rate. In males aged 12 to 18 years, valproic acid was the most common choice followed by lamotrigine, whereas lamotrigine was the first choice of ASM for females, exceeding the second and third most common options levetiracetam and oxcarbazepine by a factor of two and three, respectively.
CONCLUSION
Off-label medication is common in children with epilepsy but does not seem to be associated with lower retention. The restrictions regarding valproic acid for females of childbearing age seem to have been well implemented in Swedish neuropediatric care.
Topics: Male; Female; Humans; Child; Infant; Child, Preschool; Lamotrigine; Oxcarbazepine; Levetiracetam; Sweden; Valproic Acid; Triazines; Epilepsy; Anticonvulsants
PubMed: 37116405
DOI: 10.1016/j.pediatrneurol.2023.03.016 -
Antioxidants (Basel, Switzerland) Dec 2022Research reports using animal models of ischemic insults have demonstrated that oxcarbazepine (a carbamazepine analog: one of the anticonvulsant compounds) extends...
Therapeutic Administration of Oxcarbazepine Saves Cerebellar Purkinje Cells from Ischemia and Reperfusion Injury Induced by Cardiac Arrest through Attenuation of Oxidative Stress.
Research reports using animal models of ischemic insults have demonstrated that oxcarbazepine (a carbamazepine analog: one of the anticonvulsant compounds) extends neuroprotective effects against cerebral or forebrain injury induced by ischemia and reperfusion. However, research on protective effects against ischemia and reperfusion cerebellar injury induced by cardiac arrest (CA) and the return of spontaneous circulation has been poor. Rats were assigned to four groups as follows: (Groups 1 and 2) sham asphyxial CA and vehicle- or oxcarbazepine-treated, and (Groups 3 and 4) CA and vehicle- or oxcarbazepine-treated. Vehicle (0.3% dimethyl sulfoxide/saline) or oxcarbazepine (200 mg/kg) was administered intravenously ten minutes after the return of spontaneous circulation. In this study, CA was induced by asphyxia using vecuronium bromide (2 mg/kg). We conducted immunohistochemistry for calbindin D-28kDa and Fluoro-Jade B histofluorescence to examine Purkinje cell death induced by CA. In addition, immunohistochemistry for 4-hydroxy-2-nonenal (4HNE) was carried out to investigate CA-induced oxidative stress, and immunohistochemistry for Cu, Zn-superoxide dismutase (SOD1) and Mn-superoxide dismutase (SOD2) was performed to examine changes in endogenous antioxidant enzymes. Oxcarbazepine treatment after CA significantly increased the survival rate and improved neurological deficit when compared with vehicle-treated rats with CA (survival rates ≥ 63.6 versus 6.5%), showing that oxcarbazepine treatment dramatically protected cerebellar Purkinje cells from ischemia and reperfusion injury induced by CA. The salvation of the Purkinje cells from ischemic injury by oxcarbazepine treatment paralleled a dramatic reduction in 4HNE (an end-product of lipid peroxidation) and increased or maintained the endogenous antioxidant enzymes (SOD1 and SOD2). In brief, this study shows that therapeutic treatment with oxcarbazepine after CA apparently saved cerebellar neurons (Purkinje cells) from CA-induced neuronal death by attenuating oxidative stress and suggests that oxcarbazepine can be utilized as a therapeutic medicine for ischemia and reperfusion brain (cerebellar) injury induced by CA.
PubMed: 36552657
DOI: 10.3390/antiox11122450 -
Frontiers in Neurology 2022We performed a prospective cohort study to compare the efficacy, safety, effect on mood, and quality of life between lamotrigine (LTG) and oxcarbazepine (OXC)...
OBJECTIVE
We performed a prospective cohort study to compare the efficacy, safety, effect on mood, and quality of life between lamotrigine (LTG) and oxcarbazepine (OXC) monotherapy among Chinese adult patients with newly-diagnosed focal-onset epilepsy (FOE) with or without secondarily generalized tonic-clonic seizures.
METHODS
We enrolled 106 adult patients with new-onset FOE, of whom 56 were in the OXC group and 50 in the LTG group. Their clinical characteristics were detailly recorded especially basic seizure frequency, seizure types, and drug-related adverse events. Efficacy was evaluated as seizure-free (no seizure for 6 months), effective (seizure reduction by more than 50%), and ineffective (seizure reduction by less than 50%). Both intention-to-treat and per-protocol analyses were performed. We also assessed their mood state with the Zung Self-rating Scale for anxiety (Z-SAS) and Zung Self-rating Scale for Depression (Z-SDS) and quality of life (QOL) with Quality of Life in Epilepsy (QOLIE-31) at their baseline visit, 3-month visits, and 6-month visit. Intra-group comparisons in each group and inter-group comparisons between the two groups were made. Correlation analysis and multiple regression analysis were also conducted.
RESULTS
Except for gender, the two groups were well matched in any other characteristics such as primary seizure frequency and seizure types. In terms of efficacy, 33 patients in the OXC group were evaluated as seizure-free and 15 as effective, while in the LTG group, 31 were seizure-free, and nine were effective. No significant differences could be observed in efficacy between the two groups ( = 0.429). Through multiple logistic regression analysis, we found that OXC monotherapy was more likely to predict a seizure-free state (OR = 1.76) than LTG, but the difference didn't reach statistical significance ( = 0.322) after correcting for other clinical variables. Both groups had adverse events such as fatigue, drowsiness, dizziness, rash, and gastrointestinal discomfort, most of which were mild and transient. In the OXC group, the scores of SAS ( = 0.067) and SDS ( = 0.004) reduced at the 6-month visit, while the score of QOLIE-31 significantly increased ( = 0.001). In the LTG group, a significant decrease in SAS and SDS scores and an increase in QOLIE-31 scores could be witnessed (All < 0.001). The inter-group comparison showed that improvement of SAS and SDS in the LTG group was more evident than that in the OXC group, which was of statistical significance. Correlational analysis indicated that the improvement of mood and life quality scales in both groups was independent of baseline seizure frequency and treatment efficacy. Multiple linear regression analysis indicated that LTG monotherapy was the only independent factor that could predict a better SAS ( = 0.01) and SDS ( = 0.019) outcome.
CONCLUSIONS
OXC and LTG are effective as monotherapy and can be considered first-line selection among adult patients with new-onset FOE. Most adverse events are mild, transient, and tolerable. The two drugs improve the mood state of patients, though LTG is superior to OXC in this respect. OXC and LTG have great power in enhancing patients' quality of life. The positive effect on the psychosocial well-being of epilepsy patients may be one of the intrinsic pharmacological properties of LTG and OXC.
PubMed: 35756921
DOI: 10.3389/fneur.2022.855498 -
Epilepsia Apr 2002
Topics: Anticonvulsants; Carbamazepine; Humans; Oxcarbazepine; Porphyrias, Hepatic; Seizures
PubMed: 11952779
DOI: 10.1046/j.1528-1157.2002.d01-2_1.x