Valproic acid could help in the fight against COVID-19: A case-control study.

OBJECTIVE: There is early evidence about Valproic acid (VPA) antiviral effect. Our aim was to investigate the incidence and severity of SARS-CoV-2 infection in VPA users as compared with the general population. MATERIAL AND METHODS: A case-control study nested within a cohort, carried out between March 1 and December 17, 2020. Retrospectively, we identified confirmed SARS-CoV-2 infection patients exposed to VPA in our health department (defined as case). We ascertained VPA regimen (all the time (AT) (292 days) or at least 20% of the study period (notAT) (≥58 days) and if VPA levels were in therapeutic range (ATR) (50-100mcg/mL) in the last 24 months. We calculated the cumulative incidence of SARS-CoV-2 infection and hospital admission in the cases, comparing it with the general unexposed VPA population (controls). RESULTS: During the study period, 6183 PCR+ were detected among 281,035 inhabitants, of these, 746 were hospitalized. 691 patients were on VPA notAT and 628 (90.1%) AT. The indication for VPA use was epilepsy in 54.9%. The incidence of PCR+ was 1.736% (OR 0.785 (95%CI 0.443-1.390) and 1.910% (OR 0.865 (95%CI 0.488-1.533), on VPA notAT and VPA AT patients, respectively vs. 2.201% in people without VPA regimen. Those patients with VPA ATR had a lower risk of PCR + (OR 0.233 (95%CI 0.057-0.951) notAT; OR 0.218 (95%CI 0.053-0.890) AT). Hospital admission incidence was lower in patient on VPA (OR was 0.543 (95% CI 0.076-3.871). CONCLUSION: Patients with VPA within the therapeutic range had a reduction of SARS-Cov-2 infection incidence greater than 75%. There is a downward trend in the risk of COVID-19 admission by SARS-CoV-2 in patients on VPA therapy. These findings warrant further investigation.

Stevens-Johnson Syndrome/Toxic epidermal necrolysis complicated with fulminant type 1 diabetes mellitus: a case report and literature review.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening skin lesion triggered by hypersensitive drug reaction. They are characterized by extensive epidermal necrosis and skin exfoliation. Fulminant type 1 diabetes mellitus (FT1DM) is featured by a rapid-onset of hyperglycemia with ketoacidosis due to severely destroyed ß-cell function. Fulminant type 1 diabetes mellitus as a sequela of SJS/TEN has rarely been reported. CASE PRESENTATION: We present a 73-year-old female patient who developed SJS/TEN skin allergic reaction after taking carbamazepine and phenytoin for 35 days. Then, hyperglycemia and diabetic ketoacidosis occurred 20 days after discontinuation of antiepileptic drugs. A very low serum C-peptide level (8.79 pmol/l) and a near-normal glycosylated hemoglobin level met the diagnostic criteria for fulminant T1DM. Intravenous immunoglobulin (IVIG) and insulin were promptly administered, and the patient recovered finally. CONCLUSIONS: This rare case indicates that monitoring blood glucose is necessary in SJS/TEN drug reaction, and comprehensive therapy with rehydration, insulin, antibiotics, and IVIG may improve the prognosis.

Valproate-Autism Labyrinth.

Valproate and Autism complexity is manifold. From an established environmental risk factor for autism, to a translational animal model, valproate's composite mode of action might unfold to address core autistic domains transcending mere aggressive behavioural control.

Amnestic syndrome in the course of seronegative limbic encephalitis complicated by drug-resistant epilepsy: a case report.

We present the case of a 35-year-old female patient admitted to the hospital with symptoms of rapidly increasing disturbances of consciousness and fever for 48 hours. A lumbar puncture, bacteriological and virological examinations, and initial imaging studies did not show abnormalities. Brain magnetic resonance imaging (MRI), repeated several times, showed hyperintense confluent lesions in both temporal lobes and atrophy of both hippocampi. General examination, cerebrospinal fluid culture, the panel of antineuronal antibodies, and tumor markers remained negative on subsequent repeats. Despite several laboratory and imaging studies, the etiology of the disease could not be established, infections were excluded, and no autoantibodies were found. A diagnosis of probable limbic encephalitis, amnestic syndrome resulting from organic brain damage, and drug-resistant epilepsy was made. The patient, with limbic encephalitis complicated by drug-resistant status epilepticus, was treated with cycles of immunoglobulin and subsequent plasmapheresis. She was then transferred to the Department of Psychiatry for diagnosis and treatment of intermittent psychotic disorders. During hospitalization, the patient was observed to have multiple epileptic seizures with temporal and frontal morphology, amnestic syndrome with confabulations, and periodic psychotic disorders with the occurrence of visual hallucinations. Antiepileptic treatment was escalated by including cenobamate in increasing doses. To control the mental disorders, duloxetine, tiapride, and cognitive function exercises were introduced. There was a slight improvement in memory, a cessation of confabulations, and an emergence of the patient's criticism of the symptoms presented. The psychotic symptoms subsided, and the number of epileptic seizures decreased. The described case portrays a unique co-occurrence of disease symptoms that are difficult to treat. It shows the therapeutic difficulties that can occur in patients with suspected autoimmune encephalitis. Furthermore, it shows the need for multispecialty care of a patient with psychotic symptoms in the course of epilepsy accompanied by amnestic syndrome.

Promoting medication compliance in epileptic children: a cross sectional survey.

BACKGROUND: Compliance with medication is crucial for the favorable prognosis of children with epilepsy. The objective of this study was to assess the determinants of medication compliance and to construct a predictive model for the risk of non-compliance among pediatric epilepsy patients. METHODS: The study included children diagnosed with epilepsy and treated at our hospital between February 1 and September 30, 2023. We evaluated the demographic characteristics and medication compliance profiles of these patients. The predictive model's performance was assessed using the receiver operating characteristic (ROC) curve to determine its sensitivity and specificity. RESULTS: A total of 168 children with epilepsy were analyzed. The rate of non-compliance with medication was found to be 32.74% (55 out of 168). Logistic regression identified the educational level of parents (OR = 2.844, 95% CI: 2.182-3.214), monthly household income (OR = 1.945, 95% CI: 1.203-2.422), the number of medications taken (OR = 1.883, 95% CI: 1.314-2.201), and the level of epilepsy knowledge received (OR = 2.517, 95% CI: 1.852-3.009) as significant factors influencing non-compliance (all p < 0.05). A total score threshold of 6 was set for the predictive model. The area under the ROC curve was 0.713 (95% CI: 0.686-0.751), indicating the model's discriminative ability. CONCLUSIONS: The compliance to medication regimens among children with epilepsy is suboptimal and influenced by a multitude of factors. This study has developed a predictive model for medication compliance, which could serve as a valuable tool for clinical assessment and intervention planning regarding medication compliance in pediatric epilepsy patients.

Role of antioxidants in reducing oxidative stress and seizure frequency in drug-resistant epileptic patients.

Drug-resistant epilepsy presents significant challenges in treating epileptic patients, leading to recurrent seizures and necessitating the use of polypharmacy with anti-epileptic drugs. Both of these conditions contribute to increased oxidative stress, which is detrimental to the brain. The aim of this study was to determine the role of vitamins C and E in reducing oxidative stress and seizure frequency in drug-resistant epileptic patients. This was a double-blinded, randomized clinical trial with a placebo, parallel design, and block randomization. The subjects were drug-resistant epileptic patients aged 1-18 years who received routine treatment. Randomization was performed on 100 patients who were divided into the treatment or placebo groups. The patients received a combination of vitamin C (100 mg/day) and vitamin E (200 IU/day for those <5 years or 400 IU/day for those ≥5 years) or a placebo for eight weeks. Malondialdehyde (MDA) levels and seizure frequency were measured prior to and after the intervention. A total of 42 and 46 patients were followed till the end of the study in the intervention and placebo groups, respectively. Our data indicated that the MDA levels prior to treatment were not significantly different between the treatment and placebo groups (0.901 vs 0.890 mmol/mL, p=0.920) and were significantly reduced after the treatment in both the treatment group (p<0.001) and placebo group (p=0.028). The changes in MDA levels (between post- and pre-treatment) were also not significantly different between the two groups (p=0.181). Our per-protocol analysis indicated that the reduction in seizure frequency was significantly higher in the treatment group compared to the placebo group (95% vs 35%, p<0.001), with 92% and 60% relative and absolute risk reduction, respectively. The intention-to-treat analysis also indicated that the reduction in seizure frequency was significantly higher in the intervention group than in the control group (80% vs 32%, p<0.001), with relative and absolute risk reduction of 70% and 48%, respectively. There was no significant relationship between changes in MDA levels and seizure frequency in either group. In conclusion, vitamins C and E could reduce seizure frequency and, therefore, could be considered as adjuvant therapy in drug-resistant epileptic patients.

Clinical characteristics and post-operative outcomes in children with malformation of cortical development related drug-resistant epilepsy: 428 cases in one pediatric epilepsy center.

AIMS: To investigate post-operative seizure outcomes, and predictors of surgical outcomes of the malformation of cortical development (MCD) in children with drug-resistant epilepsy (DRE) and age-specific characteristics. METHODS: We retrospectively analyzed clinical data from 428 children with MCD-related DRE who underwent curative surgical treatment. Statistical analyses were conducted to identify correlative characteristics, prognostic predictors, and differences among various age groups. RESULTS: After more than 3 years of follow-up, 81.3% of patients achieved Engel I outcomes. Prognosis was correlated with factors such as age at surgery, MRI findings, invasive EEG, pathology, acute postoperative seizures (APOS), and the number of preoperative and postoperative anti-seizure medications (AEDs). Age at surgery and the number of preoperative AEDs (p < 0.001) were significant predictors of seizure recurrence. Distinct clinical characteristics were observed among different age groups. CONCLUSION: Surgery is effective in terminating MCD-related DRE. Younger age at surgery and fewer preoperative AEDs are associated with better prognoses. Clinical characteristics vary significantly with age.

Aetiology and Outcome of Childhood Convulsive Status Epilepticus: A tertiary care experience in Oman.

Objectives: This study aimed to evaluate the aetiology, management and outcomes of convulsive status epilepticus (CSE) in children and highlight the factors influencing patient outcomes in such cases. Methods: In a retrospective study spanning the 2020-2023 period, 93 children with CSE treated at Sultan Qaboos University Hospital's emergency department (ED), high dependency unit (HDU) and intensive care unit (ICU) were analysed. The Modified Rankin Scale at discharge was used to determine CSE outcomes. Results: Among the 93 children studied (mean age 4.84 ± 3.64 years), predominantly Omani (92.47%), 14 aetiologies were noted. Of them, acute symptomatic (37.7%) and febrile status (31.2%) were the primary causes of CSE. Diazepam was administered as the first-line treatment in 58 (67.44%) cases, with a median seizure duration of 45 minutes. Successful seizure control was achieved in 71 (76.34%) cases within 60 minutes. A return to baseline was observed in 55.9% of cases, while mortality and disability were noted in 5.38% and 38.7% of cases, respectively. For 17 cases, aetiology and duration significantly impacted patient outcomes (P <0.05). Conclusion: Acute symptomatic status is the most common aetiology of CSE. A longer duration of CSE is associated with higher mortality and neurological disability. Prompt and appropriate management of CSE is essential. Furthermore, identifying and treating the underlying cause of CSE is a crucial step in reducing its duration and improving patient outcomes.

Midazolam-Induced Seizure-Like Activity in Five Neonates: A case series.

An intravenous (IV) administration of midazolam may result in seizure-like activity or movement. This report describes 5 neonates who developed seizure-like movements after IV midazolam injection. The patients presented between 2019 and 2022 and were admitted to a neonatal intensive care unit located within an academic centre in Muscat, Oman. The abnormal movements occurred shortly after IV bolus administration of midazolam. None of the patients experienced seizure-like movements after receiving midazolam infusions. The seizure-like movements were aborted either spontaneously or by antiseizure medications. In addition, seizure recurrence was not observed in any of the infants during the later stages of their treatment. Since this adverse effect might be related to the speed of the bolus administration, IV midazolam must be given as a slow bolus over 2-3 minutes followed by a slow flush of normal saline. To prevent midazolam's potential adverse effect on newborns, neonatal caregivers must be aware of it.

What do women with epilepsy know about pregnancy?

BACKGROUND:  Understanding the intersection of epilepsy and pregnancy, including knowledge gaps and healthcare access for women with epilepsy (WWE), is critical. This study evaluated WWE knowledge gaps and information needs concerning epilepsy's impact on their sexual and reproductive health during pregnancy and examined healthcare system factors affecting their access to information, aiming to identify areas for improvement in educational and healthcare strategies to enhance health management for WWE. METHODS:  From July 2022 to June 2023, 111 WWE aged 18 to 40 years were recruited from the family medicine and internal medicine outpatient departments at Steve Biko Academic Hospital, Tembisa Tertiary Hospital (TTH), and Kalafong Hospital. Interviews assessed various aspects related to epilepsy in pregnancy and contraceptive use. RESULTS:  The study found strong links between WWE, their demographics, and their awareness of pregnancy-related epilepsy issues. Participants from TTH showed notably higher awareness (85.5%) of risks from epilepsy and AED during pregnancy (p  0.05). Age and education significantly influenced pregnancy planning and understanding of medication risks. Younger women (20-25 years) were more inclined towards future pregnancies, and those with more education were better informed about medication risks (p  0.05); and 68.5% had received counselling on AED and contraceptive interactions, yet only 16.2% knew AED could reduce contraceptive effectiveness. CONCLUSION:  The study reveals significant knowledge gaps in WWE regarding the impact of epilepsy and AED on pregnancy, suggesting tailored educational and counselling initiatives to improve WWE health outcomes and quality of life, advancing chronic disease management and public health objectives.Contribution: The study highlights substantial knowledge gaps in epilepsy during pregnancy among WWE, urging tailored counselling and information to empower informed decisions.

Increased coherence predicts medical refractoriness in patients with temporal lobe epilepsy on monotherapy.

Among patients with epilepsy, 30-40% experience recurrent seizures even after adequate antiseizure medications therapies, making them refractory. The early identification of refractory epilepsy is important to provide timely surgical treatment for these patients. In this study, we analyze interictal electroencephalography (EEG) data to predict drug refractoriness in patients with temporal lobe epilepsy (TLE) who were treated with monotherapy at the time of the first EEG acquisition. Various EEG features were extracted, including statistical measurements and interchannel coherence. Feature selection was performed to identify the optimal features, and classification was conducted using different classifiers. Functional connectivity and graph theory measurements were calculated to identify characteristics of refractory TLE. Among the 48 participants, 34 (70.8%) were responsive, while 14 (29.2%) were refractory over a mean follow-up duration of 38.5 months. Coherence feature within the gamma frequency band exhibited the most favorable performance. The light gradient boosting model, employing the mutual information filter-based feature selection method, demonstrated the highest performance (AUROC = 0.821). Compared to the responsive group, interchannel coherence displayed higher values in the refractory group. Interestingly, graph theory measurements using EEG coherence exhibited higher values in the refractory group than in the responsive group. Our study has demonstrated a promising method for the early identification of refractory TLE utilizing machine learning algorithms.

Pharmacology of Adenosine A1 Receptor Agonist in a Humanized Esterase Mouse Seizure Model Following Soman Intoxication.

Recently a novel genetically modified mouse strain with serum carboxylesterase knocked-out and the human acetylcholinesterase gene knocked-in (KIKO) was created to simulate human responses to nerve agent (NA) exposure and its standard medical treatment. A1 adenosine receptor (A1AR) agonist N-bicyclo-(2.2.1)-hept-2-yl-5'-chloro-5'-deoxyadenosine (ENBA) alone is a potent anticonvulsant and neuroprotectant (A/N) in both rat and KIKO mouse soman (GD) seizure models. In this study we utilized the KIKO mouse to evaluate further the basic pharmacologic A/N effects of ENBA as an adjunct to standard NA medical treatments (i.e., atropine sulfate, pralidoxime chloride [2-PAM], and midazolam). Male mice, implanted with cortical electroencephalographic (EEG) electrodes, were pretreated with asoxime (HI-6) and exposed to an epileptogenic dose of GD (33 µg/kg, s.c.) or saline (sham exposure) and then treated 15 min after seizure onset with ENBA at 15 mg/kg, i.p. (a minimum efficacy dose in suppressing NA-induced seizure) alone or as an adjunct to standard medical treatments. We collected EEG activity, seizure suppression outcomes, daily body temperature and weight, heart rate, toxic signs, neuropathology, and lethality data for up to 14 days. Without ENBA, death from NA exposure was 45%, while with ENBA, either alone or in combination with midazolam, the survival improved to 80% and 90%, respectively. Additionally, seizure was suppressed quickly and permanently, toxic signs, hypothermia, and bradycardia recovered by 48 h, and no neuropathology was evident. Our findings confirmed that ENBA is a potent A/N adjunct for delayed medical treatments of NA exposure.

[Withdrawal and reintroduction of pharmacological treatment of epilepsy in paediatric patients. Our experience]. / Retirada y reintroducción del tratamiento farmacológico de la epilepsia en pacientes pediátricos. Nuestra experiencia.

INTRODUCTION: There are many variables to be considered in the withdrawal of treatment for epileptic seizures, which requires a risk-benefit assessment. PATIENTS AND METHODS: A retrospective study of patients in a neuropaediatric practice who required the reintroduction of treatment for epilepsy after its initial withdrawal, and who continue to receive anti-seizure drugs. RESULTS: Twenty-three of 57 children whose treatment was withdrawn are currently being administered the treatment as a monotherapy. Attempts at withdrawal were made with 17 patients, with a mean seizure-free period of 26 months; range: 8-47 months (excluding one patient who never stopped presenting seizures). Mean age at the time of the last known data: 16 years; range: 7-28 years. Average time until the first seizure after withdrawal: 12 months; range: 1-82 months. Seizures persist despite the current treatment administered in eight cases. Two or three attempts to withdraw treatment were made in six patients, with a mean seizure-free period of 28.6 months; range: 22-48 months. Mean age at the time of the last known data: 18.68 years; range: 13-37 years. Average time until the first seizure after withdrawal: 8.2 months; range: 1-30 months. They presented seizures after treatment four was reintroduced. 52% of the patients presented seizures while receiving the drug, which was discontinued. The treatment was withdrawn in cases meeting criteria for persistent seizures: three refractory epilepsies, five symptomatic focal epilepsies, four cases with intellectual disability, five adolescent-onset epilepsies, and failures in previous withdrawal in 23 cases and 30 attempts. CONCLUSION: The decision to withdraw treatment must be personalised, and consider the risk of relapse, taking into account efficacy and tolerability, and behaviour and neurodevelopment in particular.

TITLE: Retirada y reintroducción del tratamiento farmacológico de la epilepsia en pacientes pediátricos. Nuestra experiencia.Introducción. Existen muchas variables que se deben considerar en la retirada del tratamiento anticrisis epilépticas, que precisa una evaluación riesgo-beneficio. Pacientes y métodos. Estudio retrospectivo en pacientes de una consulta de neuropediatría que precisaron reintroducir el tratamiento de la epilepsia tras su retirada inicial y continúan con fármacos anticrisis epilépticas. Resultados. De 57 niños a quienes se les retiró el tratamiento, 23 lo llevan actualmente, todos en monoterapia. En 17 se realizó un intento de retirada, con tiempo medio previo sin crisis de 26 meses; rango: 8-47 meses (excluido uno que nunca dejó de presentarlas). Edad media en el momento de los últimos datos conocidos: 16 años; rango: 7-28 años. Tiempo medio hasta nueva crisis tras retirada: 12 meses; rango: 1-82 meses. En ocho casos persisten crisis pese al tratamiento actual. En seis se realizaron 2-3 intentos, con un tiempo medio previo sin crisis de 28,6 meses; rango: 22-48 meses. Edad media en el momento de los últimos datos conocidos: 18,68 años; rango: 13-37 años. Tiempo medio hasta nueva crisis tras retirada: 8,2 meses; rango: 1-30 meses. Presentaron crisis una vez reintroducido el tratamiento cuatro. Había presentado crisis recibiendo el fármaco que se suspendió, el 52%. Se retiró el tratamiento a casos con criterios de persistencia de crisis: tres epilepsias refractarias, cinco focales sintomáticas, cuatro con discapacidad intelectual, cinco epilepsias de inicio en la adolescencia, y en 23 casos y 30 intentos fallidos en la retirada previa. Conclusión. La decisión de retirada debe ser individualizada, conociendo el riesgo de recaída, atendiendo a la eficacia y la tolerabilidad, especialmente el comportamiento y el neurodesarrollo.

[Advances and guidance in the treatment of drug-resistant epilepsy: a review by the Andalusian Epilepsy Society of the new drugs cenobamate, fenfluramine and cannabidiol]. / Avances y orientaciones en el tratamiento de la epilepsia farmacorresistente: revisión de los nuevos fármacos cenobamato, fenfluramina y cannabidiol por la Sociedad Andaluza de Epilepsia.

This review, conducted by the Andalusian Epilepsy Society, provides an update on recent advances in the treatment of drug-resistant epilepsy, focusing on three new anti-seizure drugs: cenobamate, fenfluramine and cannabidiol. These emerging drugs offer new therapeutic alternatives for patients with drug-resistant focal epilepsy, Dravet syndrome, and Lennox-Gastaut syndrome. The primary objective of this review is to provide healthcare professionals with an up-to-date overview of the efficacy, safety and potential clinical applications of these treatments, backed by the latest evidence. In addition to reviewing the available clinical evidence, the document addresses essential practical considerations for the implementation of these drugs in routine clinical practice, including aspects such as their dosage, drug interactions, and management of their side-effects. With this review, the Andalusian Epilepsy Society aims to contribute to improving the care for and quality of life of patients with drug-resistant epilepsy and their families.

TITLE: Avances y orientaciones en el tratamiento de la epilepsia farmacorresistente: revisión de los nuevos fármacos cenobamato, fenfluramina y cannabidiol por la Sociedad Andaluza de Epilepsia.Esta revisión, realizada por la Sociedad Andaluza de Epilepsia, proporciona una actualización sobre los avances recientes en el tratamiento de la epilepsia farmacorresistente y se enfoca en tres nuevos medicamentos anticrisis: cenobamato, fenfluramina y cannabidiol. Estos fármacos emergentes ofrecen nuevas opciones terapéuticas para pacientes con epilepsia focal farmacorresistente y síndromes como el de Dravet y el de Lennox-Gastaut. El objetivo principal de esta revisión es brindar a los profesionales de la salud un panorama actualizado sobre la eficacia, la seguridad y las posibles aplicaciones clínicas de estos tratamientos, respaldado por la evidencia más reciente. Además de revisar la evidencia clínica disponible, el documento aborda consideraciones prácticas esenciales para la implementación de estos fármacos en la práctica clínica diaria, incluyendo aspectos como la posología, la identificación de interacciones farmacológicas y la gestión de efectos secundarios. A través de esta revisión, la Sociedad Andaluza de Epilepsia trata de contribuir a mejorar la atención y la calidad de vida de los pacientes con epilepsia farmacorresistente y sus familias.

Effect of Levetiracetam on Oxidant-Antioxidant Activity during Long-Term Temporal Lobe Epilepsy in Rats.

Epilepsy is a disorder characterized by a predisposition to generate seizures. Levetiracetam (LEV) is an antiseizure drug that has demonstrated oxidant-antioxidant effects during the early stages of epilepsy in several animal models. However, the effect of LEV on oxidant-antioxidant activity during long-term epilepsy has not been studied. Therefore, the objective of the present study was to determine the effects of LEV on the concentrations of five antioxidant enzymes and on the levels of four oxidant stress markers in the hippocampus of rats with temporal lobe epilepsy at 5.7 months after status epilepticus (SE). The results revealed that superoxide dismutase (SOD) activity was significantly greater in the epileptic group (EPI) than in the control (CTRL), CTRL + LEV and EPI + LEV groups. No significant differences were found among the groups' oxidant markers. However, the ratios of SOD/hydrogen peroxide (H2O2), SOD/glutathione peroxidase (GPx) and SOD/GPx + catalase (CAT) were greater in the EPI group than in the CTRL and EPI + LEV groups. Additionally, there was a positive correlation between SOD activity and GPx activity in the EPI + LEV group. LEV-mediated modulation of the antioxidant system appears to be time dependent; at 5.7 months after SE, the role of LEV may be as a stabilizer of the redox state.

The Adverse Effects of Commonly Prescribed Antiseizure Medications in Adults With Newly Diagnosed Focal Epilepsy.

BACKGROUND AND OBJECTIVES: Systematic screening can help identify antiseizure medication (ASM)-associated adverse events (AEs) that may preclude patients from reaching effective doses or completing adequate trial periods. The Adverse Event Profile (AEP) is a self-completed instrument to identify the frequency of common AEs associated with ASM use. This study aimed to compare the AE profile of commonly used ASMs in adults with newly diagnosed focal epilepsy. METHODS: The Human Epilepsy Project is a prospective, international, observational study investigating markers of treatment response in newly diagnosed focal epilepsy. Participants were enrolled within 4 months of treatment initiation. Adult participants on levetiracetam, lamotrigine, carbamazepine, or oxcarbazepine monotherapy who completed the AEP and Mini International Neuropsychiatric Interview at enrollment were included. Multivariable generalized linear and penalized logistic regression models assessed differences in total and itemized marginal AEP scores and dichotomized responses ("never/rarely" vs "sometimes/always"). RESULTS: A total of 225 adults initiated on levetiracetam (n = 132, 59%), lamotrigine (n = 55, 24%), carbamazepine (n = 19, 8.4%), or oxcarbazepine (n = 19, 8.4%) were included. There were no significant differences in AEP total scores between ASMs. Patients with depression (adjusted marginal score ratio [aMSR] 1.23, 95% CI 1.09-1.39, p = 0.001) and anxiety (aMSR 1.15, 95% CI 1.04-1.26, p = 0.007) had worse AEP total scores than those without. After adjusting for depression and anxiety, levetiracetam users were >3 times more likely to report feelings of aggression (adjusted odds ratio [aOR] 3.38, 95% CI 1.07-10.7, p = 0.038) and almost half as likely to experience unsteadiness (aOR 0.45, 95% CI 0.21-0.99, p = 0.047) than lamotrigine users. Carbamazepine and oxcarbazepine had the highest rates of discontinuation (42.1%, each), followed by levetiracetam (34.8%) and lamotrigine (16.4%). Levetiracetam users had the highest proportion of discontinuations because of AEs alone (18%), and lamotrigine had the lowest (5%). DISCUSSION: Systematic screening for AEs in adults with newly diagnosed focal epilepsy on ASM monotherapy showed that those with comorbid psychiatric conditions report greater AEs overall, irrespective of ASM. Levetiracetam was associated with >3-fold risk of psychiatric AEs and half the risk of experiencing unsteadiness than lamotrigine. Levetiracetam had the highest proportion of discontinuations because of AEs alone, while lamotrigine had the lowest.

Development of a UPLC-MS/MS Method to Simultaneously Measure 13 Antiepileptic Drugs with Deuterated Internal Standards.

BACKGROUND: The goal of this study was to develop and validate a UPLC-MS/MS method for simultaneous mea-surement of 13 AEDs, including carbamazepine, oxcarbazepine, lamotrigine, levetiracetam, topiramate, primidone, zonisamide, gabapentin, lacosamide, perampanel, pregabalin, rufinamide, and vigabatrin, in whole blood samples. METHODS: A UPLC-MS/MS method for simultaneous determination of 13 AEDs in whole blood was developed, and validation was conducted for accuracy, precision, limit of quantification (LOQ), matrix effect, and stability. Our method was compared to two different hospitals using UPLC-MS/MS. RESULTS: All AEDs exhibited linearity across the AMR (analytical measurement range), with R2 values ranging from 0.994 to 1.000. The imprecision and inaccuracy for low and high quality control (QC) levels were within an acceptable range, with the coefficient of variation (CV) < 15%. The LOQ was 0.62 µg/mL for carbamazepine, 1.61 µg/mL for oxcarbazepine, 1.30 µg/mL for lamotrigine, 13.20 µg/mL for levetiracetam, 1.26 µg/mL for topira-mate, 1.01 µg/mL for primidone, 1.59 µg/mL for zonisamide, 1.09 µg/mL for lacosamide, 1.61 µg/mL for gabapentin, 0.50 µg/mL for pregabalin, 0.07 ng/mL for perampanel, 3.00 µg/mL for rufinamide, and 2.06 µg/mL for vigabatrin. All AEDs demonstrated acceptable assay parameters for carryover, stability, and matrix effects. Moreover, the assay showed satisfactory results compared to two different hospitals with a bias of less than 15%. CONCLUSIONS: We successfully developed and validated a fast and robust UPLC-MS/MS method for routine therapeutic drug monitoring of thirteen antiepileptic drugs simultaneously.

Advances in Mood Disorder Pharmacotherapy: Evaluating New Antipsychotics and Mood Stabilizers for Bipolar Disorder and Schizophrenia.

This article provides a narrative review of recent developments in mood-stabilizing drugs, considering their mechanism of action, efficacy, safety, and therapeutic potential in the treatment of mood disorders, particularly bipolar disorder and schizophrenia. The review focuses on the mechanism and clinical aspects of second-generation antipsychotic medications; aripiprazole, classified as a third-generation antipsychotic medication; lamotrigine, as a representative of antiepileptic drugs; and lurasidone, a novel second-generation antipsychotic medication. Moreover, the article refers to one of the newest and most highly effective normothymic drugs, cariprazine. The potential of new mood stabilizer candidates lumateperone and brexpiprazole is also presented. Covered topics include the clinical efficacy of new drugs in reducing manic and depressive symptoms during acute episodes, as well as their role in preventing relapse. In addition, we analyzed the incidence of adverse effects of each drug. Many of the new drugs have strong potential to be beneficial and safe in cases of many comorbidities, as they do not cause many adverse effects and do not require high doses of use. The results underscore the importance of ongoing and future research to better understand the action and efficacy of these mood stabilizers and their implications in the treatment of mood disorders, aiming to achieve euthymia and improve the quality of life of affected patients. In this article, we aim to review current drug treatments for the management of mood disorders, including bipolar disorder and schizophrenia.