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Epilepsy Research Aug 2022There have been several reports that switching formulations of antiseizure medications (ASMs) has been associated with a deterioration of seizure control, seizure...
There have been several reports that switching formulations of antiseizure medications (ASMs) has been associated with a deterioration of seizure control, seizure relapse or increased adverse effects. Considering recent findings that excipients, namely purported inactive ingredients, may nevertheless exert biological effects, it is possible that the variation in adverse event profile of antiseizure drugs may be related to differences in excipients. To test our hypothesis, we constructed a new research tool to connect FDA-compiled adverse event reports to the excipient in the medicine. Analysis of adverse events to formulations of five different second-generation antiseizure drugs - gabapentin, lamotrigine, levetiracetam, oxcarbazepine, and topiramate - showed several significant associations between specific excipient in the formulations and an adverse event when compared to the same medicine formulated with other excipients. Epilepsy and seizure adverse events were associated with multiple excipients across gabapentin, lamotrigine, and levetiracetam formulations. A different group of excipients were associated with reports of hypersensitivity reactions including urticaria, rash, erythema, and Stevens-Johnson syndrome. Our study provides a novel approach to analyzing post-market surveillance reports by including excipients. It may be useful to clinicians when evaluating select patient groups that may be refractory to pharmacological treatment or experience worsening adverse events when switching formulations of the same antiseizure medicine.
Topics: Anticonvulsants; Drug Compounding; Excipients; Gabapentin; Humans; Lamotrigine; Levetiracetam; Seizures
PubMed: 35661571
DOI: 10.1016/j.eplepsyres.2022.106947 -
Medicine Nov 2023Posterior reversible encephalopathy syndrome (PRES) is a rare complication commonly associated with headache and acute changes in blood pressure that results from a...
RATIONALE
Posterior reversible encephalopathy syndrome (PRES) is a rare complication commonly associated with headache and acute changes in blood pressure that results from a variety of causes, culminating in vasogenic cerebral edema in the occipital and parietal lobes of the brain.
PATIENT CONCERNS
We report here a woman who suffered from headache, generalized tonic-clonic seizures, and cortical blindness in the late postpartum period.
DIAGNOSES
Posterior reversible encephalopathy syndrome.
INTERVENTIONS
The patient was treated with amlodipine besylate tablets for hypertension, dehydration with mannitol and glycerin fructose, and antispasmodic treatment with sodium valproate and oxcarbazepine.
OUTCOMES
On day 2, the patient became conscious, headache and vision improved. One week later, symptoms and signs disappeared, blood pressure returned to normal, and brain MRI lesions disappeared in re-examination.
LESSONS
Eclampsia associated with PRES is reversible in most cases, but it is a serious and potentially life-threatening obstetric emergency. If adequate treatment is provided in a timely manner, most women will make a full recovery. Attention needs to be paid to timely and adequate treatment, as well as appropriate follow-up and support for patients with PRES.
Topics: Pregnancy; Humans; Female; Eclampsia; Posterior Leukoencephalopathy Syndrome; Postpartum Period; Brain Diseases; Puerperal Disorders; Headache
PubMed: 37960797
DOI: 10.1097/MD.0000000000035867 -
Experimental and Therapeutic Medicine Dec 2020This study aimed to investigate the clinical efficacy of oxcarbazepine and lamotrigine combined with escitalopram in treating patients with epilepsy and depressive...
Comparison of clinical efficacy of oxcarbazepine and lamotrigine combined with escitalopram, and impact on prognostic quality of life in treating patients with epilepsy and depressive disorder.
This study aimed to investigate the clinical efficacy of oxcarbazepine and lamotrigine combined with escitalopram in treating patients with epilepsy and depressive disorder, and their influence on the prognostic quality of life. A total of 108 patients with epilepsy and depression were selected as research participants. Among them, 53 patients were treated by oxcarbazepine combined with escitalopram (group A) and 55 patients were treated by lamotrigine combined with escitalopram (group B). Following six-month treatment, efficacy, epilepsy frequency and duration, Hamilton Depression Rating (HAMD) and Montgomery-Asberg Depression Rating (MADRS) scores, adverse reactions, improvement of electroencephalogram (EEG) epileptic discharge, quality of life, 1-year drug retention rate and withdrawal reasons of the two groups were compared. There was no remarkable difference in the total efficacy rate between both groups. The number and duration of epileptic seizures, improvement of EEG epileptic discharge and quality of life in the two groups significantly improved after treatment, with no marked difference. HAMD and MADRS scores of patients from group B were significantly lower after treatment compared with those of patients from group A. The incidence rate of adverse reactions in group B was dramatically lower compared with group A, and the 1-year drug retention rate of group B was dramatically higher compared with that in group A. Both oxcarbazepine and lamotrigine combined with escitalopram exhibited good efficacy in patients with epilepsy and depressive disorder, and they may effectively improve the prognostic quality of life of patients. Lamotrigine combined with escitalopram presented with a better antidepressant effect and safety, with higher patient tolerance.
PubMed: 33093884
DOI: 10.3892/etm.2020.9275 -
Proceedings (Baylor University. Medical... Oct 2020The primary aims of this study were to determine if oxcarbazepine is a safely tolerated option for treatment of psychiatric symptoms in children and whether its use...
The primary aims of this study were to determine if oxcarbazepine is a safely tolerated option for treatment of psychiatric symptoms in children and whether its use facilitates dose modification of other psychotropic medications. A retrospective chart review was completed using data extracted from the electronic medical record of a large outpatient child psychiatry clinic. A total of 507 of 740 children prescribed oxcarbazepine for psychiatric indications for 3 months or more had adequate data to assess clinical responses and medication outcomes. Most patients prescribed oxcarbazepine experienced clinically significant control of irritability/anger, mood stabilization, aggressive outbursts, impulsivity, or anxiety, with over 80% achieving at least maintenance symptom control. In all, 51% and 25% fully discontinued second- or third-generation antipsychotic or antidepressant medication, respectively, after starting oxcarbazepine; 8% discontinued oxcarbazepine for nonresponse, while 9% stopped oxcarbazepine because of emergent side effects. In patients fully discontinuing or reducing the second- or third-generation antipsychotic dose by 50% or more, improvements in body mass index were observed. Oxcarbazepine may prove to be an appropriate alternative to antipsychotic and antidepressant medications for treating psychiatric symptoms in children and adolescents. In particular, it may be a more metabolically neutral psychotropic medication.
PubMed: 33456141
DOI: 10.1080/08998280.2020.1826259 -
RSC Advances Feb 2021Structurally related carbamazepine (CBZ) and oxcarbazepine (OX) are two of the most commonly used antipsychotic drugs. The main impurities of CBZ, as described in both...
Appraisal of the greenness profile of a chromatographic method for the simultaneous estimation of carbamazepine and oxcarbazepine, along with two potential impurities and three formulation excipients.
Structurally related carbamazepine (CBZ) and oxcarbazepine (OX) are two of the most commonly used antipsychotic drugs. The main impurities of CBZ, as described in both the USP and the BP, are iminodibenzyl (IMD) and iminostilbene (IST). Meanwhile, for non-pharmacopeial OX, the declared impurities include CBZ and IST. Prescribed oral suspensions of CBZ and OX contain additives including methyl paraben (MP), propyl paraben (PP) and sorbic acid (SA) as preservatives. An HPTLC method was introduced and developed for resolving the interference between CBZ, OX, their impurities, and the suspension additives in a single run, in addition to their quantitation with a high sensitivity that satisfies the USP requirements for the detection and quantitation of drug impurities. In the developed HPTLC method, CBZ and OX were measured in the range of 40-4000 ng per band, while IMD, IST, MP, PP and SA were in the range of 20-2000 ng per band, using a mixture of hexane : ethylacetate : formic acid : acetic acid (8 : 2 : 0.5 : 0.3, by volume) and UV scanning at 254 nm. The greenness profile of the method was evaluated by two different tools, the analytical Eco-Scale and the Green Analytical Procedure Index (GAPI), then a comparison between their results was conducted. This is the first time that the studied drugs, along with their impurities and suspension additives, were analyzed by a HPTLC method in a single run and within the limits required by the USP guidelines.
PubMed: 35423303
DOI: 10.1039/d0ra10521j -
Molecules (Basel, Switzerland) Sep 2022A sensitive and rapid bioanalytical method based on the LC-triple-stage fragmentation (LC-MS) strategy on a hybrid triple quadrupole-linear ion trap mass spectrometer in...
Development and Validation of a Highly Sensitive and Rapid LC-MS Strategy to Determine Oxcarbazepine and Its Active Metabolite in the Serum of Patients with Epilepsy and Its Application in Therapeutic Drug Monitoring.
A sensitive and rapid bioanalytical method based on the LC-triple-stage fragmentation (LC-MS) strategy on a hybrid triple quadrupole-linear ion trap mass spectrometer in combination with protein precipitation extraction for sample pretreatment has been developed and validated for the simultaneous determination of the antiepileptic drug oxcarbazepine (OXC) and its main active metabolite (MHD) in human serum. The separation was performed on a Waters XBridge BEH C18 column (2.5 µm, 2.1 × 50 mm) in isocratic elution with 0.1% formic acid in water and methanol (50:50, ) as the mobile phase. The run time for each sample was 2.0 min. The calibration curves ranging from 25 to 1600 ng/mL for OXC and from 0.5 to 32 μg/mL for MHD showed correlation coefficients (r) better than 0.99. All of the validation data, such as precision, accuracy and other parameters, fit the requirements of the current bioanalytical method validation guidelines. The LC-MS method for quantitation of OXC and MHD was compared with the LC-MRM based method. Passing-Bablok regression coefficients and Bland-Altman plots showed that the developed LC-MS method is a reliable method for quantitative analysis of OXC and MHD. The proposed LC-MS method was successfully applied to determine the serum concentrations of OXC and MHD to support a clinical study.
Topics: Carbamazepine; Chromatography, High Pressure Liquid; Chromatography, Liquid; Drug Monitoring; Epilepsy; Humans; Oxcarbazepine; Reproducibility of Results; Tandem Mass Spectrometry
PubMed: 36080439
DOI: 10.3390/molecules27175670 -
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 -
Translational Pediatrics Apr 2021Epilepsy is the most common chronic neurological disease in children, and focal epileptic seizures are the most common subtype. Unlike the data supporting treatment...
BACKGROUND
Epilepsy is the most common chronic neurological disease in children, and focal epileptic seizures are the most common subtype. Unlike the data supporting treatment options for adults with epilepsy, evidence regarding the most effective first-line drug therapy for focal epilepsy in children and adolescents is limited. While lamotrigine is a therapeutic option for adults, there are disagreements surrounding its efficacy and tolerability in the younger population. Therefore, we performed a meta-analysis to determine if there was sufficient evidence to support a more definitive recommendation.
METHODS
We undertook electronic search strategies using Medline via Ovid SP, Embase via Ovid SP up to February 05, 2021. We also searched relevant articles through Chinese BioMedical Literature (CBM), Chinese National Knowledge Infrastructure (CNKI), WANFANG, and VIP databases up to February 05, 2021. Study selection and data extraction were performed by 2 authors independently. The randomized controlled trials on focal epilepsy in children were included, and we made risk of bias judgments based on the methods endorsed by The Cochrane Collaboration. We used fifty percent or greater reduction in seizure frequency as an indicator of efficacy, the incidence of adverse events and treatment withdrawal as indicators of tolerability. The strength of the correlation was assessed via risk ratios (RRs) and their 95% confidence intervals (95% CIs).
RESULTS
A total of 7 randomized trials involving 757 participants fulfilled the eligibility criteria. Of the 7 trials, 3 were placebo-controlled, and 4 compared lamotrigine with carbamazepine or oxcarbazepine. Lamotrigine was significantly more effective than placebo in achieving ≥50% reduction in seizure frequency, but its efficacy was not significantly different from that of carbamazepine or oxcarbazepine (lamotrigine placebo: RR 2.95, 95% CI, 1.88 to 4.61; lamotrigine carbamazepine/oxcarbazepine: RR 0.95, 95% CI, 0.85 to 1.05. There was significant difference in the incidence of overall adverse events between the lamotrigine- and carbamazepine/oxcarbazepine-treated groups (RR 0.64, 95% CI, 0.45 to 0.90).
CONCLUSIONS
Lamotrigine was effective in reducing the seizure frequency when used as an add-on treatment in children with focal epilepsy, but current evidence does not suggest that lamotrigine is superior to carbamazepine/oxcarbazepine as monotherapy. For overall adverse events, lamotrigine has significantly fewer than carbamazepine/oxcarbazepine, suggesting that lamotrigine has better tolerability.
PubMed: 34012830
DOI: 10.21037/tp-20-379 -
Frontiers in Neurology 2023No interventional study has been conducted in China to assess efficacy and safety of perampanel in treating Chinese patients with epilepsy, nor has there been any study...
BACKGROUND
No interventional study has been conducted in China to assess efficacy and safety of perampanel in treating Chinese patients with epilepsy, nor has there been any study on perampanel early add-on therapy in China. This interventional study aimed to assess efficacy and safety of perampanel as an early add-on treatment of focal-onset seizures (FOS) with or without focal-to-bilateral tonic-clonic seizures (FBTCS) in Chinese patients.
METHODS
In this multicenter, open-label, single-arm, phase 4 interventional study, Chinese patients ≥ 12 years old with FOS with or without FBTCS who failed anti-seizure medication (ASM) monotherapy from 15 hospitals in China were enrolled and treated with perampanel add-on therapy (8-week titration followed by 24-week maintenance). The primary endpoint was 50% responder rate. Secondary endpoints included seizure-freedom rate and changes in seizure frequency from baseline. Treatment-emergent adverse events (TEAEs) and drug-related TEAEs were recorded.
RESULTS
The full analysis set included 150 patients. The mean maintenance perampanel dose was 5.9 ± 1.5 mg/day and the 8-month retention rate was 72%. The 50% responder rate and seizure-freedom rate for all patients during maintenance were 67.9 and 30.5%, respectively. Patients with FBTCS had higher 50% responder rate (96.0%) and seizure-freedom rate (76.0%) during maintenance. Patients on concomitant sodium valproate had a significantly higher seizure-freedom rate than those on concomitant oxcarbazepine. Eight-six (55.1%) patients experienced treatment-related TEAEs, and the most common TEAEs were dizziness (36.5%), hypersomnia (11.5%), headache (3.9%), somnolence (3.2%), and irritability (3.2%). Withdrawal due to TEAEs occurred to 14.7% of the patients.
CONCLUSION
Perampanel early add-on was effective and safe in treating Chinese patients≥12 years old with FOS with or without FBTCS.www.chictr.org.cn, Identifier ChiCTR2000039510.
PubMed: 37712083
DOI: 10.3389/fneur.2023.1236046 -
CNS Neuroscience & Therapeutics Jul 2022This multicenter, open-label, randomized study (Registration No. ChiCTR-OCH-14004528) aimed to compare the efficacy and effects of oxcarbazepine (OXC) with levetiracetam... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy comparison of oxcarbazepine and levetiracetam monotherapy among patients with newly diagnosed focal epilepsy in China: A multicenter, open-label, randomized study.
AIMS
This multicenter, open-label, randomized study (Registration No. ChiCTR-OCH-14004528) aimed to compare the efficacy and effects of oxcarbazepine (OXC) with levetiracetam (LEV) as monotherapies on patient quality of life and mental health for patients with newly diagnosed focal epilepsy from China.
METHODS
Patients with newly diagnosed focal epilepsy who had experienced 2 or more unprovoked seizures at greater than a 24-h interval during the previous year were recruited. Participants were randomly assigned to the OXC group or LEV group. Efficacy, safety, quality of life, and mental health were evaluated over 12-week and 24-week periods.
RESULTS
In total, we recruited 271 newly diagnosed patients from 23 centers. Forty-four patients were excluded before treatment for reasons. The rate of seizure freedom of OXC was significantly superior to that of LEV at 12 weeks and 24 weeks (p < 0.05). The quality of life (except for the seizure worry subsection) and anxiety scale scores also showed significant differences from before to after treatment in the OXC and LEV groups.
CONCLUSIONS
OXC monotherapy may be more effective than LEV monotherapy in patients with newly diagnosed focal epilepsy. Both OXC and LEV could improve the quality of life and anxiety state in adult patients with focal epilepsy.
Topics: Adult; Anticonvulsants; Epilepsies, Partial; Humans; Levetiracetam; Oxcarbazepine; Quality of Life; Seizures; Treatment Outcome
PubMed: 35429132
DOI: 10.1111/cns.13840