RESUMEN

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.

Asunto(s)

Anticonvulsivantes , Diabetes Mellitus Tipo 1 , Síndrome de Stevens-Johnson , Humanos , Síndrome de Stevens-Johnson/etiología , Síndrome de Stevens-Johnson/complicaciones , Síndrome de Stevens-Johnson/diagnóstico , Femenino , Anciano , Diabetes Mellitus Tipo 1/complicaciones , Anticonvulsivantes/efectos adversos , Pronóstico , Carbamazepina/efectos adversos

RESUMEN

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.

Asunto(s)

Anticonvulsivantes , Carbamazepina , Epilepsias Parciales , Lamotrigina , Levetiracetam , Oxcarbazepina , Humanos , Femenino , Masculino , Anticonvulsivantes/efectos adversos , Epilepsias Parciales/tratamiento farmacológico , Adulto , Persona de Mediana Edad , Lamotrigina/efectos adversos , Lamotrigina/uso terapéutico , Levetiracetam/efectos adversos , Levetiracetam/uso terapéutico , Estudios Prospectivos , Carbamazepina/efectos adversos , Carbamazepina/análogos & derivados , Carbamazepina/uso terapéutico , Oxcarbazepina/efectos adversos , Adulto Joven

RESUMEN

PURPOSE: Prenatal exposure to antiseizure medications (ASMs) has been associated with an increased risk of major malformations and neurodevelopmental disorders, with the latter being mainly associated with valproate (VPA). Our aim was to compare neurocognitive outcome at age 6-7 years in children exposed prenatally to lamotrigine (LTG), carbamazepine (CBZ), valproate (VPA) or levetiracetam (LEV) monotherapy. METHODS: Eligible mother-child pairs were identified from the observational prospective multinational EURAP cohort study. Assessor-blinded testing was conducted at age 6-7 years using WISC-III and NEPSY-II. Verbal IQ (VIQ), performance IQ (PIQ), full scale IQ (FSIQ) and performance in neuropsychological tasks were compared across ASM groups by ANOVA. Scores were adjusted for maternal IQ, paternal education, maternal epilepsy type and child sex. RESULTS: Of 169 children enrolled in the study, 162 (LTG n = 80, CBZ n = 37, VPA n = 27, LEV n = 18) had sufficient data from WISC-III, NEPSY-II or both, and were included in the analyses. Observed (unadjusted) PIQ and FSIQ did not differ across exposure groups, but a difference was identified for VIQ (P<0.05), with children exposed to VPA having lower scores than children exposed to LEV (P<0.05) and children from all groups combined (P<0.01). Adjusted VIQ, PIQ and FSIQ scores did not differ significantly across groups, but VPA-exposed children had borderline significantly lower adjusted VIQ scores than children from all groups combined (P=0.051). VPA-exposed children had lower scores in comprehension of instructions before and after adjustment for confounding variables than children exposed to LTG (P<0.001), LEV (P<0.01) or children from all groups combined (p < 0.001). The VPA-exposed group also had lower scores in immediate and delayed memory for faces compared to children exposed to CBZ (P<0.05 and P<0.001, respectively) and LTG (P<0.05 and P<0.02, respectively), and children from all groups combined (P<0.02 and P<0.001, respectively). LEV-exposed children had lower scores in delayed memory for names than children exposed to LTG (P<0.001), CBZ (P<0.001), VPA (P<0.05) and children from all groups combined (P<0.001). CONCLUSIONS: Consistent with previous reports, our results provide evidence for an adverse effect of prenatal exposure to valproate on verbal development. Our finding of relatively weaker performance of VPA-exposed children compared to other ASM exposures in both comprehension of instructions and face memory also suggest that children of mothers treated with VPA are at increased risk for compromised memory functions or altered processing of socially relevant information.

Asunto(s)

Anticonvulsivantes , Carbamazepina , Epilepsia , Lamotrigina , Levetiracetam , Efectos Tardíos de la Exposición Prenatal , Ácido Valproico , Humanos , Femenino , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Anticonvulsivantes/efectos adversos , Niño , Embarazo , Masculino , Levetiracetam/efectos adversos , Ácido Valproico/efectos adversos , Lamotrigina/efectos adversos , Lamotrigina/uso terapéutico , Carbamazepina/efectos adversos , Epilepsia/tratamiento farmacológico , Pruebas Neuropsicológicas , Triazinas/efectos adversos , Estudios de Cohortes , Piracetam/análogos & derivados , Piracetam/efectos adversos , Adulto , Cognición/efectos de los fármacos , Estudios Prospectivos , Inteligencia/efectos de los fármacos

RESUMEN

Trigeminal neuralgia is a debilitating condition characterized by severe facial pain. Carbamazepine has been widely used as a first-line treatment option for trigeminal neuralgia, but there is a need to evaluate its safety and efficacy based on existing evidence. This meta-analysis aims to systematically assess the available literature and provide a comprehensive evaluation of the safety and efficacy of carbamazepine in the treatment of trigeminal neuralgia. A thorough search of electronic databases yielded a total of 15 relevant studies that met the inclusion criteria. The pooled analysis of these studies revealed that carbamazepine demonstrated significant efficacy in reducing pain intensity and frequency in patients with trigeminal neuralgia. Moreover, the drug was generally well-tolerated, with the most common adverse events being mild and transient. Subgroup analyses based on different dosages and treatment durations further supported the overall findings. However, caution should be exercised in patients with certain comorbidities or specific populations, as some rare but severe adverse events were reported. In conclusion, this meta-analysis provides strong evidence supporting the safety and efficacy of carbamazepine as a valuable therapeutic option for the management of trigeminal neuralgia. These results can guide clinicians in making informed decisions regarding the use of carbamazepine and contribute to optimizing treatment strategies for patients with trigeminal neuralgia. Further research is warranted to explore long-term safety and efficacy outcomes, as well as to compare carbamazepine with alternative treatment modalities.

Asunto(s)

Carbamazepina , Neuralgia del Trigémino , Humanos , Analgésicos no Narcóticos/uso terapéutico , Analgésicos no Narcóticos/efectos adversos , Carbamazepina/uso terapéutico , Carbamazepina/efectos adversos , Resultado del Tratamiento , Neuralgia del Trigémino/tratamiento farmacológico

RESUMEN

Genetic screening for HLA-B*15:02 before prescribing carbamazepine is standard practice to prevent severe cutaneous adverse reactions in Asian populations. These reactions are associated not only with this allele but also with closely related HLA-B75 serotype markers-HLA-B*15:11 and HLA-B*15:21-which are prevalent in several Asian countries. However, a reliable method for identifying HLA-B75 serotype markers is still not available. We developed an in-house quantitative PCR (qPCR) for HLA-B75 screening and validated it using 303 anonymized DNA samples. Due to inadequate quality control, the qPCR results for 11 samples were excluded. We analyzed the sensitivity and specificity of the test using 93 HLA-typed samples. The concordance between the qPCR method and an established screening method was assessed using 199 HLA-screened samples tested for HLA-B*15:02 at Songklanagarind Hospital, Songkhla, Thailand. All discordant results were confirmed by Sanger sequencing. The qPCR method demonstrated a sensitivity of 100% (95% confidence interval = 83.16%-100.00%) and a specificity of 100% (95% confidence interval = 95.07%-100.00%). Concordance analysis revealed a 96.5% agreement between methods (192/199; 44 positive and 148 negative results). All discordant results were due to HLA-B75 markers not being HLA-B*15:02 (two samples with HLA-B*15:11 and five samples with HLA-B*15:21). In conclusion, this qPCR method could be useful for identifying HLA-B75 carriers at risk of carbamazepine-induced reactions in Asian populations where carriers of HLA-B*15:02, HLA-B*15:11, or HLA-B*15:21 are common.

Asunto(s)

Carbamazepina , Antígeno HLA-B15 , Humanos , Carbamazepina/efectos adversos , Antígeno HLA-B15/genética , Antígeno HLA-B15/inmunología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Tailandia , Anticonvulsivantes/efectos adversos , Pueblo Asiatico/genética , Farmacogenética , Serogrupo , Sensibilidad y Especificidad , Alelos

RESUMEN

Importance: The HLA-B*15:02 allele has been associated with an increased risk of carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in specific Asian populations (including Han Chinese, Malaysian, Thai, and Vietnamese individuals). While HLA-B*15:02 genotype testing in Asian populations is recommended by several international prescribing guidelines, it is not subsidized by the Medicare Benefits Schedule in Australia. Objective: To evaluate the cost-effectiveness of HLA-B*15:02 genotyping in Asian Australian patients with epilepsy. Design, Setting, and Participants: A model with components of decision analysis and Markov simulation was developed to simulate clinical trajectories of adult Asian Australian patients with newly diagnosed epilepsy being considered for carbamazepine treatment. Cost-effectiveness and cost-utility analyses over a lifetime time horizon were conducted from the perspective of the Australian health care sector. The study was conducted in May 2023 and data analysis was performed from August 2023 to November 2023. Intervention: No HLA-B*15:02 genotyping and the empirical initiation of treatment with carbamazepine vs HLA-B*15:02 genotyping and the initiation of treatment with valproate in allele carriers. Main Outcomes and Measures: Life-years (LYs), quality-adjusted life-years (QALYs), and costs in 2023 Australian dollars (A$); incremental cost-effectiveness ratios. Results: HLA-B*15:02 screening was associated with an additional mean cost of A$114 (95% CI, -A$83 to A$374; US$76; 95% CI, -US$55 to US$248) and a reduction in 0.0152 LYs (95% CI, 0.0045 to 0.0287 LYs) but improvement by 0.00722 QALYs (95% CI, -0.0247 to -0.01210) compared with no screening, resulting in an incremental cost-effectiveness ratio of A$15 839 per QALY gained (US$10 523 per QALY). Therefore, universal genotyping for Asian Australian individuals was cost-effective compared with current standards of practice at the A$50 000 per QALY willingness-to-pay threshold. Sensitivity analyses demonstrated that the intervention remained cost-effective across a range of costs, utilities, transition probabilities, and willingness-to-pay thresholds. At the A$50 000 per QALY willingness-to-pay threshold, universal screening was the preferred strategy in 88.60% of simulations. Conclusions and Relevance: The results of this economic evaluation suggest that HLA-B*15:02 screening represents a cost-effective choice for Asian Australian patients with epilepsy who are being considered for treatment with carbamazepine.

Asunto(s)

Anticonvulsivantes , Pueblo Asiatico , Carbamazepina , Análisis Costo-Beneficio , Epilepsia , Antígeno HLA-B15 , Humanos , Epilepsia/genética , Epilepsia/tratamiento farmacológico , Epilepsia/economía , Australia , Antígeno HLA-B15/genética , Anticonvulsivantes/economía , Anticonvulsivantes/efectos adversos , Carbamazepina/economía , Carbamazepina/efectos adversos , Pueblo Asiatico/genética , Masculino , Adulto , Años de Vida Ajustados por Calidad de Vida , Femenino , Síndrome de Stevens-Johnson/genética , Síndrome de Stevens-Johnson/economía , Síndrome de Stevens-Johnson/etnología , Genotipo , Persona de Mediana Edad

RESUMEN

By developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy, the Dutch Pharmacogenetics Working Group (DPWG) aims to advance the implementation of pharmacogenetics (PGx). This guideline outlines the gene-drug interaction of CYP2C9 and HLA-B with phenytoin, HLA-A and HLA-B with carbamazepine and HLA-B with oxcarbazepine and lamotrigine. A systematic review was performed and pharmacotherapeutic recommendations were developed. For CYP2C9 intermediate and poor metabolisers, the DPWG recommends lowering the daily dose of phenytoin and adjust based on effect and serum concentration after 7-10 days. For HLA-B*15:02 carriers, the risk of severe cutaneous adverse events associated with phenytoin, carbamazepine, oxcarbazepine, and lamotrigine is strongly increased. For carbamazepine, this risk is also increased in HLA-B*15:11 and HLA-A*31:01 carriers. For HLA-B*15:02, HLA-B*15:11 and HLA-A*31:01 positive patients, the DPWG recommends choosing an alternative anti-epileptic drug. If not possible, it is recommended to advise the patient to report any rash while using carbamazepine, lamotrigine, oxcarbazepine or phenytoin immediately. Carbamazepine should not be used in an HLA-B*15:02 positive patient. DPWG considers CYP2C9 genotyping before the start of phenytoin "essential" for toxicity prevention. For patients with an ancestry in which the abovementioned HLA-alleles are prevalent, the DPWG considers HLA-B*15:02 genotyping before the start of carbamazepine, phenytoin, oxcarbazepine, and lamotrigine "beneficial", as well as genotyping for HLA-B*15:11 and HLA-A*31:01 before initiating carbamazepine.

Asunto(s)

Anticonvulsivantes , Carbamazepina , Citocromo P-450 CYP2C9 , Antígenos HLA-A , Antígenos HLA-B , Humanos , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Citocromo P-450 CYP2C9/genética , Antígenos HLA-B/genética , Antígenos HLA-A/genética , Carbamazepina/efectos adversos , Carbamazepina/uso terapéutico , Lamotrigina/uso terapéutico , Oxcarbazepina , Países Bajos , Fenitoína/efectos adversos , Farmacogenética

RESUMEN

Exposure at conception to phenytoin (PHT), phenobarbital (PB), and carbamazepine (CBZ) has been associated with several different effects on the fetus, including hypoplasia of the distal phalanges, dysmorphic facial features, and structural abnormalities such as oral clefts and neural tube defects. One question is whether each of these antiepileptic drugs (AEDs) has the same effects or just similar effects. A systematic examination of the fingers of children exposed at conception to PHT, PB, or CBZ, as monotherapy, has been used to address this question. The findings in the examinations of the fingers of 115 AED-exposed children (40, PHT; 34, PB; 41, CBZ) and their parents were compared to the findings in 111 age- and sex-matched children and their parents. The evaluations used were both subjective assessments and objective measurements. Shortening and narrowing of the fifth fingernail and an increased frequency of arch patterns in the dermal ridges were more common in PHT-exposed children. A significant decrease in the length of the nail, but not width, occurred in the PB-exposed children. Stiffness of the interphalangeal joints was more common in the CBZ-exposed children. The findings in children exposed to PHT, PB, or CBZ, as monotherapy, showed that all three exposures in early pregnancy affected the fingers, but the effects were not the same. The most striking effects were present in PHT-exposed children.

Asunto(s)

Anticonvulsivantes , Carbamazepina , Dedos , Fenobarbital , Fenitoína , Efectos Tardíos de la Exposición Prenatal , Humanos , Carbamazepina/efectos adversos , Fenitoína/efectos adversos , Femenino , Fenobarbital/efectos adversos , Embarazo , Dedos/anomalías , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Masculino , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/patología , Niño , Anomalías Inducidas por Medicamentos/patología , Preescolar , Uñas/efectos de los fármacos , Uñas/patología , Lactante

Asunto(s)

Anticonvulsivantes , Carbamazepina , Síndrome de Stevens-Johnson , Humanos , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/administración & dosificación , Carbamazepina/efectos adversos , Carbamazepina/administración & dosificación , Progresión de la Enfermedad , Síndrome de Stevens-Johnson/etiología

RESUMEN

INTRODUCTION: Adverse skin reactions due to drugs such as Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) occur in 3% of people receiving anti epileptic drugs (AED). Although SJS/TEN has a low incidence, the mortality and morbidity rates are high. Indonesia has not adopted HLA-B*1502 screening prior to administration of carbamazepine (CBZ), although previous studies found a relationship between HLA-B*1502 and SJS/TEN. METHODS: A hybrid decision tree and Markov model was developed to evaluate three strategies for treating newly diagnosed focal epilepsy: CBZ direct therapy, levetiracetam (LEV) direct therapy, and therapy based on HLA-B*15:02 test results. From a societal perspective, base case and sensitivity analyses were carried out over a lifetime. RESULTS: Direct administration of CBZ appears to have a slightly lower average cost than the HLA-B*15:02 allele screening strategy. The increase in quality-adjusted life year (QALY) in HLA-B*15:02 screening before treatment related to the cost difference reached 0.519 with an incremental cost-effectiveness ratio (ICER) of around USD 984 per unit of QALY acquisition. Direct treatment of LEV increased treatment costs by almost USD 2000 on average compared to the standard CBZ strategy. The increase in QALY is 0.834 in direct levetiracetam treatment, with an ICER of around USD 2230 for each QALY processing. CONCLUSION: Calculation of the cost-effectiveness of lifetime epilepsy therapy in this study found that the initial screening strategy with the HLA-B*15:02 test was the most cost-effective.

Asunto(s)

Anticonvulsivantes , Epilepsia , Antígeno HLA-B15 , Adulto , Femenino , Humanos , Masculino , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/economía , Carbamazepina/uso terapéutico , Carbamazepina/economía , Carbamazepina/efectos adversos , Análisis de Costo-Efectividad , Árboles de Decisión , Epilepsia/economía , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Antígeno HLA-B15/genética , Indonesia/epidemiología , Levetiracetam/uso terapéutico , Cadenas de Markov , Piracetam/uso terapéutico , Piracetam/análogos & derivados , Años de Vida Ajustados por Calidad de Vida

RESUMEN

Trigeminal neuralgia is characterized by severe, lightning-like attacks of pain, which are mandatory for the diagnosis. The pain typically occurs on one side and is often triggered by simply touching the face, chewing or talking. In acute exacerbations, this can also hinder food and fluid intake, resulting in a life-threatening clinical picture. A distinction is made between classical, secondary and idiopathic trigeminal neuralgia. For the diagnosis of trigeminal neuralgia, the medical history and imaging procedures are key for classification. The only active substances approved for the treatment of trigeminal neuralgia in Germany are carbamazepine and phenytoin, which is why off-label drugs often need to be used if there is no or insufficient effect or inacceptable side effects. Cooperation between research and clinical practice to improve the care of affected patients is therefore essential.

Asunto(s)

Carbamazepina , Fenitoína , Neuralgia del Trigémino , Humanos , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/efectos adversos , Carbamazepina/uso terapéutico , Carbamazepina/efectos adversos , Conducta Cooperativa , Diagnóstico Diferencial , Alemania , Adhesión a Directriz , Comunicación Interdisciplinaria , Colaboración Intersectorial , Uso Fuera de lo Indicado , Fenitoína/uso terapéutico , Fenitoína/efectos adversos , Guías de Práctica Clínica como Asunto , Neuralgia del Trigémino/tratamiento farmacológico , Neuralgia del Trigémino/diagnóstico

RESUMEN

OBJECTIVE: Epilepsy is a chronic disease that requires long-term monitoring and treatment. It is suspected that there is a interaction between the use of anti-seizure medications and the risk of cardiovascular disease. The aim of the study is to investigate the association between the intake of phenobarbital, carbamazepine and valproic acid and their serum drug concentrations (SDC) with various cardiovascular risk parameters (homocysteine, folic acid, vitamin B12, total cholesterol (TC), triglycerides, high- and low-density lipoprotein (LDL)). METHODS: This is a cross-sectional study. Data (demographic characteristics and laboratory results) of patients treated for epilepsy in a tertiary care hospital between January 2020 and February 2022 were analyzed retrospectively (n = 2014). Kruskal Wallis, Mann-Whitney U, correlation analysis was used, p < 0.05 was considered statistically significant. RESULTS: The median age of patients was 15 years (IQR:8-31) and 48.3 % were women. The highest homocysteine level was found in patients receiving valproic acid, but it was not statistically significant. Patients receiving phenobarbital had the highest levels of folic acid and B12 and the lowest levels of total cholesterol and low-density lipoprotein cholesterol, which was statistically significant. In patients receiving carbamazepine, a moderately negative significant association was found between serum drug concentration and folic acid levels and a moderately positive significant association was found between TC and LDL levels. CONCLUSION: In our study, the majority of patients were children and adolescents. Regular monitoring of drug serum concentrations and metabolic parameters may be useful to select the safest drug in terms of cardiovascular disease risk. Randomized controlled trials on the long-term effects of anti-seizure treatment are needed.

Asunto(s)

Anticonvulsivantes , Carbamazepina , Enfermedades Cardiovasculares , Epilepsia , Ácido Valproico , Humanos , Femenino , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/sangre , Anticonvulsivantes/efectos adversos , Estudios Transversales , Masculino , Adulto , Epilepsia/tratamiento farmacológico , Epilepsia/sangre , Adolescente , Adulto Joven , Ácido Valproico/uso terapéutico , Ácido Valproico/efectos adversos , Ácido Valproico/sangre , Enfermedades Cardiovasculares/sangre , Niño , Carbamazepina/uso terapéutico , Carbamazepina/sangre , Carbamazepina/efectos adversos , Homocisteína/sangre , Fenobarbital/uso terapéutico , Fenobarbital/sangre , Estudios Retrospectivos , Vitamina B 12/sangre , Factores de Riesgo de Enfermedad Cardiaca , Ácido Fólico/sangre

RESUMEN

Importance: Women with epilepsy (WWE) require treatment with antiseizure medications (ASMs) during pregnancy, which may be associated with an increased risk of major congenital malformations (MCMs) in their offspring. Objective: To investigate the prevalence of MCMs after prenatal exposure to 8 commonly used ASM monotherapies and changes in MCM prevalence over time. Design, Setting, and Participants: This was a prospective, observational, longitudinal cohort study conducted from June 1999 to October 2022. Since 1999, physicians from more than 40 countries enrolled ASM-treated WWE before pregnancy outcome was known and followed up their offspring until 1 year after birth. Participants aged 14 to 55 years who were exposed to 8 of the most frequently used ASMs during pregnancy were included in this study. Data were analyzed from April to September 2023. Exposure: Maternal use of ASMs at conception. Main Outcomes and Measures: MCMs were assessed 1 year after birth by a committee blinded to type of exposure. Teratogenic outcomes across exposures were compared by random-effects logistic regression adjusting for potential confounders and prognostic factors. Results: A total of 10 121 prospective pregnancies exposed to ASM monotherapy met eligibility criteria. Of those, 9840 were exposed to the 8 most frequently used ASMs. The 9840 pregnancies occurred in 8483 women (mean [range] age, 30.1 [14.1-55.2] years). MCMs occurred in 153 of 1549 pregnancies for valproate (9.9%; 95% CI, 8.5%-11.5%), 9 of 142 for phenytoin (6.3%; 95% CI, 3.4%-11.6%), 21 of 338 for phenobarbital (6.2%; 95% CI, 4.1%-9.3%), 121 of 2255 for carbamazepine (5.4%; 95% CI, 4.5%-6.4%), 10 of 204 for topiramate (4.9%; 95% CI, 2.7%-8.8%), 110 of 3584 for lamotrigine (3.1%; 95% CI, 2.5%-3.7%), 13 of 443 for oxcarbazepine (2.9%; 95% CI, 1.7%-5.0%), and 33 of 1325 for levetiracetam (2.5%; 95% CI, 1.8%-3.5%). For valproate, phenobarbital, and carbamazepine, there was a significant increase in the prevalence of MCMs associated with increasing dose of the ASM. Overall prevalence of MCMs decreased from 6.1% (153 of 2505) during the period 1998 to 2004 to 3.7% (76 of 2054) during the period 2015 to 2022. This decrease over time was significant in univariable logistic analysis but not after adjustment for changes in ASM exposure pattern. Conclusions and Relevance: Of all ASMs with meaningful data, the lowest prevalence of MCMs was observed in offspring exposed to levetiracetam, oxcarbazepine, and lamotrigine. Prevalence of MCMs was higher with phenytoin, valproate, carbamazepine, and phenobarbital, and dose dependent for the latter 3 ASMs. The shift in exposure pattern over time with a declining exposure to valproate and carbamazepine and greater use of lamotrigine and levetiracetam was associated with a 39% decline in prevalence of MCMs, a finding that has major public health implications.

Asunto(s)

Anomalías Inducidas por Medicamentos , Anticonvulsivantes , Epilepsia , Complicaciones del Embarazo , Humanos , Femenino , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Adulto , Embarazo , Adulto Joven , Adolescente , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Anomalías Inducidas por Medicamentos/epidemiología , Anomalías Inducidas por Medicamentos/etiología , Persona de Mediana Edad , Estudios Longitudinales , Complicaciones del Embarazo/tratamiento farmacológico , Complicaciones del Embarazo/epidemiología , Estudios Prospectivos , Ácido Valproico/efectos adversos , Ácido Valproico/uso terapéutico , Efectos Tardíos de la Exposición Prenatal/epidemiología , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Fenitoína/efectos adversos , Fenitoína/uso terapéutico , Lamotrigina/efectos adversos , Lamotrigina/uso terapéutico , Carbamazepina/efectos adversos , Fenobarbital/efectos adversos , Fenobarbital/uso terapéutico , Estudios de Cohortes , Oxcarbazepina/efectos adversos , Oxcarbazepina/uso terapéutico , Prevalencia

RESUMEN

PURPOSE: This umbrella review was conducted to summarize the association between HLA*1502 allele with antiepileptic induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). METHODS: Pubmed, Scopus and EMBASE were searched for eligible reviews in May 2023. Two authors independently screened titles and abstracts and assessed full-text reviews for eligibility. The quality of meta-analyses and case-control studies was appraised with Assessing the Methodological Quality of Systematic Reviews 2 and Newcastle-Ottawa Scale, respectively. Narrative summaries of each antiepileptic drug were analyzed. Preestablished protocol was registered on the International Prospective Register of Systematic Reviews Registry(ID: CRD42023403957). RESULTS: Included studies are systematic reviews, meta-analyses and case-control studies evaluating the association of HLA-B*1502 allele with the following antiepileptics. Seven meta-analyses for carbamazepine, three meta-analyses for lamotrigine (LTG), three case-control studies for oxcarbazepine, nine case-control studies for phenytoin and four case-control studies for phenobarbitone were included. The findings of this umbrella review suggest that there is a strong association between HLA-B-1502 with SJS/TEN for carbamazepine and oxcarbazepine and a milder association for lamotrigine and phenytoin. CONCLUSION: In summary, although HLA-B*1502 is less likely to be associated with phenytoin or lamotrigine-induced SJS/TEN compared to carbamazepine-induced SJS/TEN, it is a significant risk factor that if carefully screened, could potentially reduce the development of SJS/TEN. In view of potential morbidity and mortality, HLA-B*1502 testing may be beneficial in patients who are initiating lamotrigine/phenytoin therapy. However, further studies are required to examine the association of other alleles with the development of SJS/TEN and to explore the possibility of genome-wide association studies before initiation of treatment.

Asunto(s)

Anticonvulsivantes , Antígeno HLA-B15 , Síndrome de Stevens-Johnson , Síndrome de Stevens-Johnson/genética , Síndrome de Stevens-Johnson/etiología , Humanos , Anticonvulsivantes/efectos adversos , Antígeno HLA-B15/genética , Carbamazepina/efectos adversos , Lamotrigina/efectos adversos , Predisposición Genética a la Enfermedad , Alelos

RESUMEN

Pharmacogenetic testing benefits patients by predicting drug efficacy and risk of adverse drug reactions (ADRs). Pharmacogenetic biomarkers useful in clinical practice include drug-metabolizing enzyme and drug transporter genes and human leukocyte antigen (HLA) genes. HLA genes, which are important molecules involved in human immunity, have long been analyzed for associations with ADRs, such as skin rash, drug-induced liver injury, and agranulocytosis. HLA is composed of many genes, each of which has dozens of different types (alleles), and many HLA alleles associated with ADRs have been reported. The odds ratios in the association of HLA alleles range from approximately 5 to several thousand, indicating a very large impact on the risk of ADRs. Thus, HLA genetic testing prior to initiation of drug therapy is expected to make a significant contribution to avoiding ADRs, but to demonstrate the clinical utility, it is necessary to prospectively show the effects of medical interventions based on the test results. We conducted the GENCAT study, a prospective, multicenter, single-arm clinical trial to investigate the impact of a therapeutic intervention based on the HLA-A*31:01 test on the incidence of carbamazepine-induced skin rash. HLA-A*31:01-positive patients were treated with an alternative drug such as valproic acid, and the study showed an approximately 60% reduction in the incidence of carbamazepine-induced skin rash. It is expected that the genetic test, which has demonstrated clinical utility, will lead to the establishment of safer and more appropriate stratified medicine by reflecting the information in clinical practice guidelines.

Asunto(s)

Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Exantema , Humanos , Pruebas de Farmacogenómica , Estudios Prospectivos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Carbamazepina/efectos adversos , Antígenos HLA-A/genética

RESUMEN

OBJECTIVE: A diagnosis of epilepsy has been associated with adverse cardiovascular events (CEs), but the extent to which antiseizure medications (ASMs) may contribute to this is not well understood. The aim of this study was to compare the risk of adverse CEs associated with ASM in patients with epilepsy (PWE). METHODS: A retrospective case-control cohort study was conducted using TriNetX, a global health federated network of anonymized patient records. Patients older than 18 years, with a diagnosis of epilepsy (International Classification of Diseases, 10th Revision code G40) and a medication code of carbamazepine, lamotrigine, or valproate were compared. Patients with cardiovascular disease prior to the diagnosis of epilepsy were excluded. Cohorts were 1:1 propensity score matched (PSM) according to age, sex, ethnicity, hypertension, heart failure, atherosclerotic heart disease, atrial and cardiac arrythmias, diabetes, disorders of lipoprotein metabolism, obesity, schizophrenia and bipolar disorder, medications, and epilepsy classification. The primary outcome was a composite of adverse CEs (ischemic stroke, acute ischemic heart disease, and heart failure) at 10 years. Cox regression analyses were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) following 1:1 PSM. RESULTS: Of 374 950 PWE included; three cohorts were established after PSM: (1) carbamazepine compared to lamotrigine, n = 4722, mean age 37.4 years; (2) valproate compared to lamotrigine, n = 5478, mean age 33.9 years; and (3) valproate compared to carbamazepine, n = 4544, mean age 37.0 years. Carbamazepine and valproate use were associated with significantly higher risk of composite cardiovascular outcome compared to lamotrigine (HR = 1.390, 95% CI = 1.160-1.665 and HR = 1.264, 95% CI = 1.050-1.521, respectively). Valproate was associated with a 10-year higher risk of all-cause death than carbamazepine (HR = 1.226, 95% CI = 1.017-1.478), but risk of other events was not significantly different. SIGNIFICANCE: Carbamazepine and valproate were associated with increased CE risks compared to lamotrigine. Cardiovascular risk factor monitoring and careful follow-up should be considered for these patients.

Asunto(s)

Anticonvulsivantes , Carbamazepina , Enfermedades Cardiovasculares , Epilepsia , Lamotrigina , Humanos , Femenino , Masculino , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/inducido químicamente , Persona de Mediana Edad , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Estudios Retrospectivos , Adulto , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Carbamazepina/efectos adversos , Carbamazepina/uso terapéutico , Lamotrigina/uso terapéutico , Lamotrigina/efectos adversos , Estudios de Casos y Controles , Anciano , Ácido Valproico/efectos adversos , Ácido Valproico/uso terapéutico , Salud Global/estadística & datos numéricos , Estudios de Cohortes

RESUMEN

OBJECTIVE: This study aimed to determine the minimum interaction between different antiepileptic drugs (AEDs) and meropenem (MEPM) for clinical treatment. PATIENTS AND METHODS: The data of 91 patients enrolled in the neurology department from January 2020 to March 2023 for clinical trials were measured and observed. Self-controlled studies were conducted to monitor the trough concentrations of valproic acid (VPA), carbamazepine (CBZ) and levotiracetam (LEV) before and after MEPM usage. Relevant indicators of liver and kidney function were also monitored. RESULTS: The serum VPA trough concentrations were 36.25±8.22 µg/ml at 24±12 h and 34.99±11.17 µg/ml at 96±12 h after MEPM use; the difference was significant (p<0.05). Decreased CBZ trough concentrations were also identified after MEPM usage (96±12 h), whereas LEV trough concentrations were not affected. An increased liver injury rate (χ2 =8.744, p<0.05) and a decreased kidney injury rate (χ2 =5.393, p<0.05) were found in the VPA group only. CONCLUSIONS: The interaction between VPA and MEPM decreased serum VPA concentrations, increased liver injury rates, and decreased kidney injury rates. In addition, the co-administration of MEPM and CBZ reduced serum CBZ concentrations. Clinicians should be aware of this potential interaction and closely monitor the relevant biochemical indices and number of seizures.

Asunto(s)

Anticonvulsivantes , Ácido Valproico , Humanos , Anticonvulsivantes/uso terapéutico , Meropenem , Estudios Prospectivos , Centros de Atención Terciaria , Ácido Valproico/efectos adversos , Carbamazepina/efectos adversos , Interacciones Farmacológicas

RESUMEN

Due to the limited number of studies in children with focal epilepsy and the importance of choosing the most suitable drug to control seizures in children, the administration of the most effective medication with the most negligible adverse events is vital. This study aimed to evaluate the effectiveness and adverse events of carbamazepine vs. levetiracetam monotherapy in children with focal seizures. A monocentric, randomized, controlled, double-blind, parallel-group clinical trial was designed. This study was approved by the Iranian Registry of Clinical Trials (registration number: IRCT20170216032603N2) on June 19, 2020, and conducted at the neurology department of Imam Ali Hospital, Karaj, Iran, from February 2020 to March 2021. This study assessed 120 patients with recently diagnosed focal seizures aged 2 to 14. Patients were randomly divided into two groups, who received carbamazepine (CBZ) 15 to 20 mg/kg and levetiracetam (LEV) 20 to 40 mg/kg daily, respectively. Patients were evaluated for improvement and complications at weeks 4, 12, and 24. Out of 120 patients included in the study, six patients were excluded due to various complications of CBZ. The mean number of seizures at the end of the fourth, twelfth, and twenty-fourth weeks were 1.09 ± 0.75, 0.62 ± 0.27, and 0.39 ± 0.12 in the carbamazepine group and 1.11 ± 0.63, 0.52 ± 0.21, and 0.37 ± 0.11 in the LEV group, respectively (P > 0.05). Similarly, the number of seizure-free patients was 34, 44, and 48 in the CBZ group compared to 41, 50, and 54 in the LEV group, respectively (P > 0.05). On the other hand, the frequency of somnolence, dermatologic complications, and agitation was considerably higher in the CBZ group (P < 0.05). Although both medicines were equally effective in seizure control, CBZ was associated with considerably more adverse events and less patient compliance. Physicians should be aware of this difference to prevent unwanted consequences.

Asunto(s)

Anticonvulsivantes , Carbamazepina , Epilepsias Parciales , Levetiracetam , Humanos , Levetiracetam/uso terapéutico , Levetiracetam/efectos adversos , Carbamazepina/efectos adversos , Carbamazepina/uso terapéutico , Niño , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/administración & dosificación , Masculino , Femenino , Epilepsias Parciales/tratamiento farmacológico , Adolescente , Preescolar , Método Doble Ciego , Resultado del Tratamiento , Irán

RESUMEN

INTRODUCTION: Trigeminal neuralgia is a rare condition characterised by paroxysms of intense pain in the distribution of the trigeminal nerve. This condition significantly diminishes the patient's quality of life, and the side effects from chronic use of medications for symptomatic relief further exacerbate their distress. CASE DESCRIPTION: The case report discusses a patient diagnosed with Trigeminal Neuralgia who commenced carbamazepine treatment. The report tracks the disease's progression, medication adjustments, and the eventual emergence of vertigo due to long-term carbamazepine use. CONCLUSION: The article covers fundamental information about trigeminal neuralgia and its management and also offers a comprehensive review of the basics of vertigo. It delves into carbamazepine's mechanism of action and its associated side effects. The paper also looks at prospective therapy changes that could improve patients' quality of life.

Asunto(s)

Carbamazepina , Neuralgia del Trigémino , Humanos , Neuralgia del Trigémino/tratamiento farmacológico , Neuralgia del Trigémino/diagnóstico , Carbamazepina/efectos adversos , Analgésicos no Narcóticos/efectos adversos , Calidad de Vida , Femenino , Vértigo/inducido químicamente , Persona de Mediana Edad , Masculino

RESUMEN

OBJECTIVE: To compare the efficacy and safety of pregabalin and carbamazepine in patients with central post-stroke pain (CPSP). METHODS: Patients included in the study were randomly assigned to either flexible-dose pregabalin treatment group or carbamazepine treatment group. The primary efficacy variable was face visual analog scale (F-VAS), the second efficacy assessment was used to assess the effect of treatment on mental health by Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD). RESULTS: The mean baseline pain score F-VAS was 6.47 in the pregabalin group and 6.58 in carbamazepine treatment group. F-VAS was significantly lower in the pregabalin group (1.64) than (3.94) carbamazepine treatment group after treatment. Pregabalin was significantly superior to carbamazepine in endpoint assessments on the HAMA and HAMD after treatment. F-VAS and HAMD were showed efficacy as early as week 2 and maintained for whole duration of the study. The average pregabalin dose in the 12-week study was 214.6 (150-375) mg/day. The mean dose (range) of carbamazepine received by the patients was 275.0 (200-400) mg/day. Mild or moderate, typically transient, somnolence and dizziness were the most common adverse events (AES). The differences of the side effects between the two groups were not significant. CONCLUSIONS: Pregabalin, but not carbamazepine, may be effective in improving F-VAS, HAMA and HAMD in patients with CPSP.

Asunto(s)

Analgésicos , Neuralgia , Humanos , Pregabalina/efectos adversos , Analgésicos/efectos adversos , Ácido gamma-Aminobutírico , Resultado del Tratamiento , Neuralgia/tratamiento farmacológico , Carbamazepina/efectos adversos , Benzodiazepinas , Método Doble Ciego