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International Journal of Molecular... Jan 2022An estimated 60 million people worldwide suffer from epilepsy, half of whom are women. About one-third of women with epilepsy are of childbearing age. The childbirth... (Review)
Review
An estimated 60 million people worldwide suffer from epilepsy, half of whom are women. About one-third of women with epilepsy are of childbearing age. The childbirth rate in women with epilepsy is about 20-40% lower compared to that of the general population, which may be partly due to a lower number of these women being in relationships. Lower fertility in women with epilepsy may be linked to the disease itself, but it is mainly a result of the treatment provided. Valproate, as an antiepileptic drug inhibiting histone deacetylases, may affect the expression of genes associated with cell cycle control and cellular differentiation. Evidently, this drug is associated with the risk of malformations although other antiepileptic drugs (AEDs) may also trigger birth defects, however, to a lower degree. Valproate (and to a certain degree other AEDs) may induce autism spectrum disorders and attention deficit hyperactivity disorder. The main mechanism responsible for all negative effects of prenatal exposure to valproate seems inhibition of histone deacetylases. Animal studies show a reduction in the expression of genes involved in social behavior and an increase in hippocampal cytokines. Valproate-induced oxidative stress may also contribute to neural tube defects. Interestingly, paternal exposure to this AED in mice may trigger neurodevelopmental disorders as well although a population-based cohort study does not confirm this effect. To lower the risk of congenital malformations and neurodevelopmental disorders, a single AED at the optimal dose and supplementation with folic acid is recommended. VPA should be avoided in women of childbearing age and especially during pregnancy.
Topics: Abnormalities, Drug-Induced; Anticonvulsants; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Epilepsy; Female; Folic Acid; Histone Deacetylase Inhibitors; Humans; Neural Tube Defects; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Valproic Acid
PubMed: 35163292
DOI: 10.3390/ijms23031369 -
Critical Care (London, England) Jan 2023Generalised convulsive status epilepticus (GCSE) is a medical emergency. Guidelines recommend a stepwise strategy of benzodiazepines followed by a second-line... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Generalised convulsive status epilepticus (GCSE) is a medical emergency. Guidelines recommend a stepwise strategy of benzodiazepines followed by a second-line anti-seizure medicine (ASM). However, GCSE is uncontrolled in 20-40% patients and is associated with protracted hospitalisation, disability, and mortality. The objective was to determine whether valproic acid (VPA) as complementary treatment to the stepwise strategy improves the outcomes of patients with de novo established GCSE.
METHODS
This was a multicentre, double-blind, randomised controlled trial in 244 adults admitted to intensive care units for GCSE in 16 French hospitals between 2013 and 2018. Patients received standard care of benzodiazepine and a second-line ASM (except VPA). Intervention patients received a 30 mg/kg VPA loading dose, then a 1 mg/kg/h 12 h infusion, whilst the placebo group received an identical intravenous administration of 0.9% saline as a bolus and continuous infusion. Primary outcome was proportion of patients discharged from hospital by day 15. The secondary outcomes were seizure control, adverse events, and cognition at day 90.
RESULTS
A total of 126 (52%) and 118 (48%) patients were included in the VPA and placebo groups. 224 (93%) and 227 (93%) received a first-line and a second-line ASM before VPA or placebo infusion. There was no between-group difference for patients hospital-discharged at day 15 [VPA, 77 (61%) versus placebo, 72 (61%), adjusted relative risk 1.04; 95% confidence interval (0.89-1.19); p = 0.58]. There were no between-group differences for secondary outcomes.
CONCLUSIONS
VPA added to the recommended strategy for adult GCSE is well tolerated but did not increase the proportion of patients hospital-discharged by day 15.
TRIAL REGISTRATION NO
NCT01791868 (ClinicalTrials.gov registry), registered: 15 February 2012.
Topics: Adult; Humans; Valproic Acid; Benzodiazepines; Hospitalization; Patient Discharge; Administration, Intravenous
PubMed: 36624526
DOI: 10.1186/s13054-022-04292-7 -
Pediatric Neurology Sep 2019Valproic acid is one of the most commonly used antiseizure medications. Multiple hematologic abnormalities have been reported with the use of valproic acid, which may be... (Review)
Review
BACKGROUND
Valproic acid is one of the most commonly used antiseizure medications. Multiple hematologic abnormalities have been reported with the use of valproic acid, which may be particularly relevant in the perioperative surgical setting. The incidence of these abnormalities and prevalence of periprocedural hemorrhage vary significantly in the published literature. In this article we analyze the prevalence and possible etiology of coagulopathy and hemorrhage in patients receiving valproic acid.
METHODS
A literature search was completed using "VPA," "coagulopathy," and "surgery." The available published data from case reports to large case series were reviewed.
RESULTS
Thrombocytopenia was noted to be the most common laboratory abnormality associated with valproic acid. An association between valproic acid and acquired von Willebrand disease has also been suggested. There are case reports describing bleeding in the setting of hypofibrinogenemia and factor XIII deficiency. Perioperative hemorrhage was reported in pediatric studies of orthopedic procedures, but not in adult cohorts undergoing neurosurgical interventions.
CONCLUSIONS
VPA use can cause thrombocytopenia and other coagulation abnormalities. Rigorous, prospective trials are needed to better assess the association between valproic acid and clinically significant coagulopathy. Until such data are available, physicians need to be aware of the potential risk of bleeding in patients receiving valproic acid. A hemostatic evaluation should be considered in symptomatic patients, and may be considered for patients taking VPA who are scheduled for surgery. If an abnormality is detected, hematologists should be involved to make recommendation on perioperative hemostatic strategy.
Topics: Anticonvulsants; Blood Coagulation Disorders; Hemostasis; Humans; Valproic Acid
PubMed: 31201069
DOI: 10.1016/j.pediatrneurol.2019.04.019 -
Journal of Clinical Pathology Aug 2023Hyperammonaemia (HA) as a consequence of numerous primary or secondary causes, gives rise to clinical manifestations due to its toxic effects on the brain. The... (Review)
Review
Hyperammonaemia (HA) as a consequence of numerous primary or secondary causes, gives rise to clinical manifestations due to its toxic effects on the brain. The neurological consequences broadly reflect the ammonia level, duration and age, with paediatric patients being more susceptible. Drug-induced HA may arise due to either decreased ammonia elimination or increased production. This is associated most frequently with use of valproate and presents a dilemma between ongoing therapeutic need, toxicity and the possibility of an alternative cause. As there is no specific test for drug-induced HA, prompt discussion with a metabolic physician is recommended, as the neurotoxic effects are time-dependent. Specific guidelines for managing drug-induced HA have yet to be published and hence the treatment approach outlined in this review reflects that outlined in relevant urea cycle disorder guidelines.
Topics: Humans; Child; Hyperammonemia; Ammonia; Brain; Valproic Acid
PubMed: 37164630
DOI: 10.1136/jcp-2022-208644 -
Issues in Mental Health Nursing Nov 2022
Topics: Humans; Valproic Acid; Delirium; Brain Injuries, Traumatic
PubMed: 36136610
DOI: 10.1080/01612840.2022.2122431 -
Current Neuropharmacology 2023
Topics: Humans; Valproic Acid; Bipolar Disorder; Lithium; Antimanic Agents; Lithium Compounds
PubMed: 37203193
DOI: 10.2174/1570159X2104230307123319 -
ChemMedChem Feb 2023Paracetamol and valproic acid are standalone drugs with leading position in the world drug market. The phosphonate analogues of these drugs were synthesized and were...
Paracetamol and valproic acid are standalone drugs with leading position in the world drug market. The phosphonate analogues of these drugs were synthesized and were tested in vivo. N-(4-hydroxyphenylcarbamoyl)phosphonic acid was four times more potent than paracetamol in preventing acetic acid-induced writhing. Phosphonate derivative of valproic acid, (2-propylpentanoyl)phosphonic acid, had similar in vivo activity to valproic acid in the pentylenetetrazole-induced kindling mouse model.
Topics: Mice; Animals; Valproic Acid; Acetaminophen; Organophosphonates; Phosphorous Acids
PubMed: 36367256
DOI: 10.1002/cmdc.202200526 -
Advanced Emergency Nursing Journal 2020Migraine headaches can be a disabling condition for patients. Fortunately, most patients can be successfully managed in the outpatient setting, however, there are a... (Review)
Review
Migraine headaches can be a disabling condition for patients. Fortunately, most patients can be successfully managed in the outpatient setting, however, there are a number of patients who may not respond to the abortive treatments that they have been prescribed. These patients often present to the emergency department (ED) for further assistance with the management of their condition. Migraines are the fourth most common cause of ED visits and are associated with an estimated annual cost of $17 billion in the United States. Familiarity with abortive treatments is critical for providers in the ED as are treatments, such as valproic acid, that may be considered in patients who do not respond to other treatment options. Many providers are more familiar with the role of valproic acid in the treatment of mood and seizure disorders, but its tolerability and the successes reported in the primary literature make it a reasonable consideration for patients with migraine who fail to respond to other therapies. This article briefly summarizes the therapies considered first line for abortive treatment in the setting of migraines and provides an overview of the primary literature describing the use of valproic acid in these patients.
Topics: Emergency Service, Hospital; GABA Agents; Humans; Migraine Disorders; Valproic Acid
PubMed: 33105176
DOI: 10.1097/TME.0000000000000319 -
Journal of Healthcare Engineering 2022Glioma is one of the most common intracranial tumors worldwide, and metastasis and chemoresistance remain a challenge in glioma treatment. This study aims to investigate...
Glioma is one of the most common intracranial tumors worldwide, and metastasis and chemoresistance remain a challenge in glioma treatment. This study aims to investigate the effect of sodium valproate on the invasion and metastasis of glioma cells and its mechanism. Glioma cell lines were stimulated with VPA at different concentrations and for different durations of action. U87 glioma cells were transfected with Smad4 plasmid and small interfering RNA, and the changes of EMT-related protein indexes in U87 cells after up- or downregulation of Smad4 were detected by Western blotting. Immunohistochemistry was used to detect the differences in the expression of Smad4, TIF1-, and TGF- proteins in 39 glioma clinical specimens from the Department of Pathology of our hospital. Based on the regulation of EMT-related transcription factors by VPA, our study indicates that VPA inhibits the EMT process of glioma by altering the expression level of Smad4, which is induced by TGF-1 to form a Smad3/4 complex, thus inducing the EMT process of the tumor and acting as an antitumor target to inhibit the invasive ability of glioma cells. Sodium valproate inhibits glioma invasion and metastasis through the regulation of Smad4 expression.
Topics: Brain Neoplasms; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Glioma; Humans; Valproic Acid
PubMed: 35251569
DOI: 10.1155/2022/4985781 -
Therapeutic Drug Monitoring Jun 2022This therapeutic drug monitoring (TDM) grand round describes a patient with serious valproic acid intoxication. A total valproic acid level of 844 mg/L and an unbound...
This therapeutic drug monitoring (TDM) grand round describes a patient with serious valproic acid intoxication. A total valproic acid level of 844 mg/L and an unbound valproic acid level of 604 mg/L were observed. Meropenem was administered to enhance the clearance of valproic acid. This off-label usage of meropenem is based on the drug-drug interaction between carbapenems and valproic acid, which reduced the level of valproic acid within 24 hours after administration.
Topics: Anti-Bacterial Agents; Anticonvulsants; Drug Interactions; Humans; Meropenem; Valproic Acid
PubMed: 35170557
DOI: 10.1097/FTD.0000000000000973