Article
Pharmacology & Pharmacy
Ming-Lu Wang, Yu-Ying Tao, Xiao-Yu Sun, Yang Guo, Zhan-You Wang, Yun-Feng Cao, Limei Zhao
Summary: During pregnancy, a refined population pharmacokinetic model of lamotrigine (LTG) in women with epilepsy was developed to identify factors influencing pharmacokinetics and establish individualized dosing regimens. Changes in estrogen profile were found to be a major contributor to variations in LTG clearance, with specific genetic variants also impacting drug clearance. The refined model incorporating estrogen profiles and pharmacogenetics outperformed a simplified model based on clinical variables alone.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Jessica M. Barry, Jacqueline A. French, Page B. Pennell, Ashwin Karanam, Cynthia L. Harden, Angela K. Birnbaum
Summary: This study aims to investigate the complexity of maintaining seizure control with lamotrigine during pregnancy and evaluate the potential risks of different dosing scenarios. The results suggest that some dosing regimens may increase seizure risk or toxicity. Early clearance changes during pregnancy may require therapeutic drug monitoring to determine whether the patient belongs to the low clearance change group or the high clearance change group.
Review
Clinical Neurology
Rebecca Knight, Anja Wittkowski, Rebecca Louise Bromley
Summary: Recent research has shown that exposure to certain newer antiseizure medications (ASMs) such as lamotrigine and levetiracetam during pregnancy does not appear to have a significant impact on child neurodevelopment. However, due to limitations in study quality and data availability, further research is needed to fully understand the effects of other ASMs on child neurodevelopment.
Review
Pharmacology & Pharmacy
Charul Avachat, Jessica M. Barry, Xintian Lyu, Catherine M. Sherwin, Angela K. Birnbaum
Summary: The management of seizures during pregnancy is crucial due to the potential risks of altered drug exposure and neurodevelopmental outcomes. While newer anti-seizure medications have more favorable pharmacokinetics, therapeutic monitoring of drug concentrations is still necessary for pregnant patients.
Article
Pharmacology & Pharmacy
P. A. Bhavatharini, Shri G. Sanghavi, Grace Thomas, K. P. Arun
Summary: This study aimed to develop a pharmacometric model-based framework for recommending an optimal dosage regimen for lamotrigine in pregnancy. Through simulations and data analysis, the drug exposure in different trimesters of pregnancy was determined, and corresponding dosage recommendations were proposed.
JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Ian E. Templeton, Karen Rowland-Yeo, Hannah M. Jones, Christopher J. Endres, Ariel R. Topletz-Erickson, Hao Sun, Anthony J. Lee
Summary: A physiologically-based pharmacokinetic (PBPK) model was developed to simulate plasma concentrations of tucatinib. The model accurately predicted tucatinib concentrations and drug-drug interactions in different scenarios after refinement and validation with clinical data.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Chemistry, Multidisciplinary
Yunjiao Wu, Swantje Voller, Elke H. J. Krekels, Daniella W. E. Roofthooft, Sinno H. P. Simons, Dick Tibboel, Robert B. Flint, Catherijne A. J. Knibbe
Summary: This study aimed to quantify the maturation of paracetamol elimination pathways in preterm neonates born below 32 weeks of gestation. The results showed that birthweight and postnatal age were the most important factors affecting paracetamol clearance and its glucuronidation, sulfation, and oxidation. Therefore, dosing based on bodyweight alone will not lead to consistent paracetamol concentrations among preterm neonates.
PHARMACEUTICAL RESEARCH
(2023)
Article
Clinical Neurology
Blanca Vazquez, Torbjorn Tomson, Cindy Dobrinsky, Edgar Schuck, Terence J. O'Brien
Summary: The study summarized pregnancy and fetal/postnatal outcomes following maternal perampanel exposure using preclinical and clinical data, and utilized physiologically based pharmacokinetic (PBPK) modeling to improve understanding of perampanel pharmacokinetics (PK) during pregnancy. Preclinical studies showed potential links between perampanel and specific physical development delays in pregnant animals. Clinical data from 96 pregnancies indicated a variety of outcomes, with some adverse events reported in full-term neonates. PK simulations predicted lower perampanel exposure levels towards the end of pregnancy compared to non-pregnant women. Further outcome data is needed to fully understand the prevalence of adverse pregnancy outcomes with perampanel exposure.
Article
Clinical Neurology
Lars Vedel Kessing, Simon Christoffer Ziersen, Thomas Gerds, Esben Budtz-Jorgensen
Summary: This nationwide population-based longitudinal register linkage study aimed to investigate the long-term response to lithium in patients with bipolar disorder with and without comorbid epilepsy. The study also aimed to compare differences in responses between lithium, valproate, and lamotrigine within patients with comorbid bipolar disorder and epilepsy. The findings suggest that valproate and lamotrigine should be given priority in these patients.
JOURNAL OF AFFECTIVE DISORDERS
(2022)
Article
Medicine, Research & Experimental
Ivana Kacirova, Milan Grundmann, Hana Brozmanova
Summary: This study analysed the concentrations of lamotrigine in maternal serum, colostrum, and serum of breastfed newborns. The findings showed that exposure to lamotrigine in breastfed newborns is lower than exposure during pregnancy. However, the concentrations of lamotrigine in both maternal serum and milk significantly increase after delivery. This may be due to the immature function of eliminating enzymes in newborns. Therefore, it is not mandatory to monitor the serum concentrations of lamotrigine in breastfed newborns, but analysis should be conducted if signs of possible adverse events are noted.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Medicine, General & Internal
Yiqian Chen, Jingzhen Chen, Xiaorong Zhuang, Xingyu Chen, Jianqi Zeng, Ru Wang, Jiayin Miao
Summary: The aim of this study was to examine the effect of lamotrigine on blood ammonia level in epilepsy patients and identify the risk factors affecting blood ammonia level. The results showed that LTG combined with valproic acid therapy, seizure within 1 year, and elevated neutrophils may be risk factors for elevated blood ammonia level in epilepsy patients treated with LTG.
Article
Clinical Neurology
Page B. Pennell, Ashwin Karanam, Kimford J. Meador, Elizabeth Gerard, Laura Kalayjian, Patricia Penovich, Abigail Matthews, Thomas M. McElrath, Angela K. Birnbaum
Summary: This study aims to characterize the changes in concentration of antiseizure medications during pregnancy. The results show that dose-normalized concentrations during pregnancy are significantly decreased compared to postpartum values, suggesting the need for increasing doses of these medications throughout pregnancy.
Article
Biochemical Research Methods
Karolina E. Kolaczynska, Matthias E. Liechti, Urs Duthaler
Summary: A rapid LC-MS/MS method was developed and validated for quantifying psilocin and its metabolite 4-HIAA in human plasma, showing good accuracy and precision over three validation runs. This method could assess the pharmacokinetics of psilocin and 4-HIAA and facilitate the clinical development of psilocybin.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2021)
Article
Polymer Science
Maria Riaz, Muhammad Zaman, Huma Hameed, Hafiz Shoaib Sarwar, Mahtab Ahmad Khan, Ali Irfan, Gamal A. Shazly, Ana Claudia Paiva-Santos, Yousef A. Bin Jardan
Summary: The study focused on preparing and evaluating a thermo-responsive sol-gel for intranasal drug delivery of lamotrigine. The sol-gel was designed for sustained drug release to treat epilepsy. The optimized formulations of sol-gel showed clarity, appropriate pH, viscosity, gelation temperature, and drug content. In vitro drug release studies indicated that the formulations released up to 92% of the drug within 24 hours. The sol-gel was also found to be stable at room temperature. Histological studies showed no toxicity in vital organs. The results suggest that the prepared intranasal sol-gel is a safe and effective alternative for epilepsy treatment.
Review
Pharmacology & Pharmacy
Sofie A. M. Brookhuis, Karel Allegaert, Lidwien M. Hanff, Marjolijn N. Lub-de Hooge, Andre Dallmann, Paola Mian
Summary: This review provides an overview of acetaminophen pharmacokinetics changes during pregnancy, showing an increase in distribution volume and clearance of acetaminophen in pregnant women compared to non-pregnant women. Gaps in knowledge, such as fetal and placental pharmacokinetic parameters, have been identified for further exploration before evidence-based dosing adjustments can be suggested.
Article
Clinical Neurology
Johan Zelano, Line Sveberg, Erik Tauboll, Torbjorn Tomson
Summary: The survey revealed that only about half of neurologists in Sweden and Norway were familiar with the EMA restrictions on VPA use, and while some had prescribed VPA to women of childbearing age in the past two years, only a small minority utilized the information brochure and risk acknowledgment forms provided by the companies. More information campaigns and closer collaboration with treating physicians may be necessary to improve awareness and compliance.
ACTA NEUROLOGICA SCANDINAVICA
(2022)
Article
Clinical Neurology
Le Zhang, Ettore Beghi, Torbjorn Tomson, Massimiliano Beghi, Giuseppe Erba, Zheng Chang
Summary: The study compared mortality, comorbidities, and causes of death in individuals with PNES, epilepsy, and the general population. Results showed that PNES patients had a significantly higher all-cause mortality rate compared to controls, with higher risks of both natural and non-natural causes of death, particularly suicide. This association varied with age and time since diagnosis.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Article
Oncology
Christopher M. Melen, Magali Merrien, Agata M. Wasik, Georgios Panagiotidis, Olof Beck, Kristina Sonnevi, Henna-Riikka Junlen, Birger Christensson, Birgitta Sander, Bjorn Engelbrekt Wahlin
Summary: This phase II clinical trial found that a one-time dose of THC/CBD can temporarily reduce leukemic B cells, but also affects normal cells. However, this dose showed no significant therapeutic potential for indolent B cell lymphomas.
LEUKEMIA & LYMPHOMA
(2022)
Article
Clinical Neurology
Julie Werenberg Dreier, Thomas Munk Laursen, Torbjorn Tomson, Oleguer Plana-Ripoll, Jakob Christensen
Summary: People with epilepsy have a higher mortality rate compared to the general population, resulting in a reduced life expectancy of around 12 years. The causes of death vary, but psychiatric comorbidity and modifiable risk factors such as accidents and cardiovascular disorders contribute significantly to the excess mortality. Preventive measures should focus on addressing these factors to reduce epilepsy-related deaths.
Article
Clinical Neurology
Tommy Stodberg, Torbjorn Tomson, Britt-Marie Anderlid, Tomas Andersson, Olivia Henry, Per Amark, Anna Wedell
Summary: Infantile-onset epilepsy carries a worse prognosis, with only half of the children achieving seizure remission and the other half having intellectual disability. Etiology is a major predictor of outcome.
Article
Behavioral Sciences
Ali A. Asadi-Pooya, Eugen Trinka, Francesco Brigo, Coraline Hingray, Ioannis Karakis, Simona Lattanzi, Kette D. Valente, Guilca Contreras, Saule T. Turuspekova, Nirmeen Adel Kishk, Ghaieb Aljandeel, Mohsen Farazdaghi, Yamile Calle Lopez, Najib Kissani, Chahnez Triki, Gunter Kraemer, Rainer Surges, Boulenouar Mesraoua, Hsiang-Yu Yu, Anilu Daza-Restrepo, Taoufik Alsaadi, Abdullah Al-Asmi, Mansur A. Kutlubaev, Chrisma Pretorius, Asel Jusupova, Samson G. Khachatryan, Lakshmi Narasimhan Ranganathan, Abdulaziz Ashkanani, Torbjorn Tomson, David Gigineishvili
Summary: This study investigates the opinions and attitudes of neurologists worldwide regarding counseling about sudden unexpected death in epilepsy (SUDEP). The results indicate that many neurologists rarely discuss the risk of SUDEP with patients and their caregivers, suggesting a severe lack of attention to this matter.
EPILEPSY & BEHAVIOR
(2022)
Article
Clinical Neurology
Claire Taylor, Catrin Tudur-Smith, Pete Dixon, Christine Linehan, Aleksei Gunko, Jakob Christensen, Mike Pearson, Torbjorn Tomson, Anthony Marson
Summary: This study conducted an audit of care provided to seizure patients in emergency departments across Europe and found significant variability in various aspects of care. The study recommends the development of guidelines for the management and referral of seizure patients in emergency departments, the establishment of a simple and easily implementable referral process, ensuring timely access to seizure services, and the implementation of a monitoring system for key indices of epilepsy care.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Silje Alvestad, Elisabeth Synnove Nilsen Husebye, Jakob Christensen, Julie Werenberg Dreier, Yuelian Sun, Jannicke Igland, Maarit Leinonen, Mika Gissler, Nils Erik Gilhus, Torbjorn Tomson, Marte Bjork
Summary: In women with epilepsy treated with antiseizure medication, periconceptional folic acid supplementation is associated with a lower risk of preterm birth.
Article
Clinical Neurology
Meir Bialer, Svein Johannessen, Matthias J. Koepp, Rene H. Levy, Emilio Perucca, Piero Perucca, Torbjorn Tomson, H. Steve White
Summary: The Sixteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVI) was recently held in Madrid, Spain, where delegates from 26 countries gathered to discuss and present investigational compounds for the treatment of seizures and epilepsy. This progress report focuses on seven compounds in advanced clinical development, including ganaxolone which has been approved by the US FDA for the treatment of seizures associated with CDKL5 deficiency disorder. The report provides a summary of recent findings and current knowledge on these compounds.
Article
Clinical Neurology
Olafur Sveinsson, Tomas Andersson, Sofia Carlsson, Torbjorn Tomson
Summary: This population-based case-control study found that perinatal factors, such as being small for gestational age and having a low Apgar score at 10 minutes, are associated with an increased risk of sudden unexpected death in epilepsy (SUDEP).
Article
Clinical Neurology
Jakob Christensen, Julie Werenberg Dreier, Yuelian Sun, Christine Linehan, Torbjorn Tomson, Anthony Marson, Lars Forsgren, Claudia A. Granbichler, Eugen Trinka, Catrinel Illiescu, Kristina Malmgren, Jakob Kjellberg, Rikke Ibsen, Poul Jorgen Jennum
Summary: This study estimated the prevalence, psychiatric co-morbidity, and annual costs associated with epilepsy in Denmark. The results showed an epilepsy prevalence of 0.67%, with 37.4% of epilepsy patients having a psychiatric disorder or using drugs for psychiatric disorders. The estimated annual individual net costs associated with epilepsy were €30,683.
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
(2023)
Article
Obstetrics & Gynecology
Paul Madley-Dowd, Jessica Rast, Viktor H. H. Ahlqvist, Caichen Zhong, Florence Z. Z. Martin, Neil M. M. Davies, Kristen Lyall, Craig Newschaffer, Torbjorn Tomson, Cecilia Magnusson, Dheeraj Rai, Brian K. K. Lee, Harriet Forbes
Summary: This study examined the prescription of antiseizure medication (ASM) during pregnancy and found an increase in prescription rates, especially among women with indications other than epilepsy. Continuous use of ASMs during pregnancy was more common in women with epilepsy. Factors associated with discontinuation included age ≥35, higher social deprivation, frequent contact with the GP, and prescription of antidepressants or antipsychotics.
BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
(2023)
Editorial Material
Clinical Neurology
Marte-Helene Bjork, Torbjoern Tomson, Julie Werenberg Dreier, Silje Alvestad, Nils Erik Gilhus, Mika Gissler, Jannicke Igland, Maarit K. Leinonen, Yuelian Sun, Hakon Magne Vegrim, Helga Zoega, Jakob Christensen
Summary: Women taking antiseizure medication during pregnancy are often advised to take high doses of folic acid supplements (1mg to 5mg) to minimize the risk of birth defects. However, a recent report has shown a link between high dose folic acid intake and an increased risk of childhood cancer in the offspring. This has sparked a debate regarding the recommended dose of folic acid for pregnant women on antiseizure medication. In this Commentary, the authors explain their findings, the methodology used, and address emerging questions.
Article
Clinical Neurology
Torbjoern Tomson, Johan Zelano, Yew Li Dang, Piero Perucca
Summary: The pharmacological treatment of epilepsy requires careful risk-benefit analysis to make critical decisions on when to initiate treatment and which antiseizure medication to use. Many factors, such as the patient's type of epilepsy, efficacy spectrum, age, sex, comorbidities, and concomitant medications, need to be considered when selecting a medication. The maintenance dose and titration scheme are individualized based on clinical response, with a preference for slow titration and the lowest effective dose. In cases of treatment failure, alternative monotherapy or combination therapy can be considered, and other treatment modalities should be explored for truly drug-resistant patients. Withdrawal of antiseizure medication also requires careful risk-benefit analysis.
EPILEPTIC DISORDERS
(2023)
Article
Clinical Neurology
Johan Zelano, Sandor Beniczky, Philippe Ryvlin, Rainer Surges, Torbjorn Tomson, ILAE SUDEP Task Force
Summary: Wearable seizure detection devices have the potential to address the needs of people with epilepsy, particularly those with tonic-clonic seizures. However, there is a lack of national guidelines and clinical practices regarding the prescription and reimbursement of these devices. A survey conducted among ILAE chapters and physicians worldwide revealed a need for international clinical practice guidelines and standardized reimbursement schemes for seizure detection devices.
