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The Journal of Pediatrics Dec 2023
Topics: Humans; Valproic Acid; Anticonvulsants
PubMed: 37541425
DOI: 10.1016/j.jpeds.2023.113660 -
The Australian and New Zealand Journal... Sep 2019
Topics: Anticonvulsants; Epilepsy; Europe; Female; Humans; Valproic Acid
PubMed: 30848662
DOI: 10.1177/0004867419834357 -
The Annals of Pharmacotherapy Mar 2021Analgesics, sedatives, and antipsychotics are commonly prescribed for agitation and delirium in the intensive care unit (ICU), but their use is limited by adverse...
BACKGROUND
Analgesics, sedatives, and antipsychotics are commonly prescribed for agitation and delirium in the intensive care unit (ICU), but their use is limited by adverse effects and lack of efficacy. Valproic acid is an alternative treatment option.
OBJECTIVE
The primary objective of this study was to describe valproic acid prescribing in our institution's ICUs when used for agitation or delirium. Measures of effectiveness and safety were also assessed.
METHODS
This was a single-center, retrospective, institutional review board-approved cohort study of adult inpatients admitted to the ICU between January 2018 and August 2018. Patients who received valproic acid for the treatment of agitation or delirium for ≥24 hours were included. Prescribing practices were evaluated for dose, frequency, and route of administration. Effectiveness was assessed via agitation and delirium assessment tools and quantity of adjunctive agents used.
RESULTS
A total of 80 patients were included, with 35 receiving valproic acid alone and 45 in conjunction with antipsychotics. The most common valproic acid regimen was 250 mg orally 3 times daily. Delirium resolution occurred in 55% of patients: 24 in the valproic acid monotherapy group and 20 in the valproic acid plus antipsychotic group (69% vs 44%; = 0.03). The incidence of delirium decreased from valproic acid day 0 to day 3 (93% vs 68%; < 0.01), with no change in agitation (64% vs 63%; = 0.28).
CONCLUSION AND RELEVANCE
Valproic acid is frequently prescribed in agitated, delirious patients at our institution and may have a role in the management of ICU delirium.
Topics: Aged; Anticonvulsants; Antipsychotic Agents; Cohort Studies; Female; Humans; Incidence; Intensive Care Units; Male; Middle Aged; Psychomotor Agitation; Retrospective Studies; Valproic Acid
PubMed: 32748626
DOI: 10.1177/1060028020947173 -
Acta Neurologica Scandinavica Apr 2021We investigated the correlation between socioeconomic status and the prescription of Valproic acid (VPA) in women of fertile age in Sweden.
OBJECTIVE
We investigated the correlation between socioeconomic status and the prescription of Valproic acid (VPA) in women of fertile age in Sweden.
METHODS
This is a registered-based cohort study including all women living in Sweden aged 18-45 years in the years 2010-2015, with a diagnosis of epilepsy and no intellectual disability (n = 9143). Data were collected from the National Patient Register, the Drug Prescription Register, and the Longitudinal integration database for health insurance and labor market studies (LISA).
RESULTS
Women with only 9 years of school were more often prescribed VPA than women with a University degree (12.9% compared to 10.7% in 2015 [p = 0.015]). Similar differences were seen between the lowest and highest income group (16.6% compared to 12.7% in 2015 [p < 0.001]). The odds of having a VPA prescription in 2015 was 1.59 (p < 0.001) in women with 9 years of school compared to women with a University degree, and 1.60 (p < 0.001) in the lowest income group relative to the highest income group after adjusting for age. From 2010 to 2015, the proportion with VPA prescription in the whole cohort diminished with an absolute reduction of -2.2% (p < 0.001). The decrease was similar among the different education and income groups (p = 0.919 and p = 0.280).
SIGNIFICANCE
The results indicate that the increased knowledge on VPA teratogenicity was implemented across socioeconomic strata in the Swedish healthcare system. Women with lower income or education level remained more frequent VPA users. Whether this difference reflects epilepsy type or severity, or socioeconomic disparities, merit further study.
Topics: Adolescent; Adult; Anticonvulsants; Cohort Studies; Drug Prescriptions; Educational Status; Epilepsy; Female; Humans; Income; Male; Middle Aged; Sweden; Valproic Acid; Young Adult
PubMed: 33523460
DOI: 10.1111/ane.13397 -
Drug and Chemical Toxicology May 2022Oxidative stress and mitochondrial dysfunction have been associated with valproic acid (VPA) induced neurotoxicity. Mitochondria are vulnerable to oxidative damage and...
Oxidative stress and mitochondrial dysfunction have been associated with valproic acid (VPA) induced neurotoxicity. Mitochondria are vulnerable to oxidative damage and are also a major source of superoxide free radicals. Therefore, the need for mitochondrial protective and antioxidant agents for reducing valporic acid toxicity in central nerve system (CNS) is essential. In the present study, we investigated the potential beneficial effects of sodium selenite (SS) and L-carnitine (LC) against valproic acid -induced oxidative stress and mitochondrial dysfunction in isolated rat cortical neurons. Valproic acid (50, 100 and 200 µM) treatment caused a significant decrease in cellular viability, which was accompanied by increases in reactive oxygen species (ROS) generation, GSSG and GSH content, lipid peroxidation and lysosomal and mitochondrial damages. Sodium selenite (1 µM) and L-carnitine (1 mM) pretreatment attenuated valproic acid-induced decrease in cell viability. In addition, sodium selenite (1 µM) and L-carnitine (1 mM) pretreatment significantly protected against valproic acid-induced raise in oxidative stress, mitochondrial and lysosomal dysfunction, lipid peroxidation levels and depletion of GSH content. Our results in the current study provided insights into the protective mechanism by L-carnitine and sodium selenite, which is liked, to neuronal ROS generation and mitochondrial and lysosomal damages.
Topics: Animals; Carnitine; Neurons; Oxidative Stress; Rats; Reactive Oxygen Species; Selenium; Sodium Selenite; Valproic Acid
PubMed: 32885679
DOI: 10.1080/01480545.2020.1810259 -
Dalton Transactions (Cambridge, England... Aug 2023The complex [PtCl(cyclohexane-1,2-diamine)] has been combined in a Pt(IV) molecule with two different bioactive molecules (, the histone deacetylase inhibitor...
The complex [PtCl(cyclohexane-1,2-diamine)] has been combined in a Pt(IV) molecule with two different bioactive molecules (, the histone deacetylase inhibitor 2-propylpentanoic acid or valproic acid, VPA, and the potential antimetastatic molecule 4-isopropenylcyclohexene-1-carboxylic acid or perillic acid, PA) in order to obtain a set of multiaction or multitarget antiproliferative agents. In addition to traditional thermal synthetic procedures, microwave-assisted heating was used to speed up their preparation. All Pt(IV) complexes showed antiproliferative activity on four human colon cancer cell lines (namely HCT116, HCT8, RKO and HT29) in the nanomolar range, considerably better than those of [PtCl(cyclohexane-1,2-diamine)], VPA, PA, and the reference drug oxaliplatin. The synthesized complexes showed pro-apoptotic and pro-necrotic effects and the ability to induce cell cycle alterations. Moreover, the downregulation of histone deacetylase activity, leading to an increase in histone H3 and H4 levels, and the antimigratory activity, indicated by the reduction of the levels of matrix metalloproteinases MMP2 and MMP9, demonstrated the multiaction nature of the complexes, which showed biological properties similar to or better than those of VPA and PA, but at lower concentrations, probably due to the lipophilicity of the combo molecule that increases the intracellular concentration of the single components (, [PtCl(cyclohexane-1,2-diamine)], VPA and PA).
Topics: Platinum; Prodrugs; Diamines; Valproic Acid; Colonic Neoplasms; Humans; Cell Line, Tumor; Histone Deacetylases; Cell Movement; Antineoplastic Agents
PubMed: 37530512
DOI: 10.1039/d3dt01876h -
JAMA Network Open May 2024Teratogenic outcomes associated with valproic acid use represent a substantial concern for persons of childbearing age. Regulatory agencies worldwide have enhanced...
IMPORTANCE
Teratogenic outcomes associated with valproic acid use represent a substantial concern for persons of childbearing age. Regulatory agencies worldwide have enhanced warnings or implemented risk minimization programs to reduce exposure during pregnancy.
OBJECTIVES
To determine pregnancy rates during valproic acid use and concomitant contraception use across indications.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study used data from the Merative MarketScan commercial claims databases from January 1, 2005, to December 31, 2020, to identify female patients aged 12 to 44 years who initiated valproic acid treatment and had continuous insurance enrollment 6 months before initiation and 9 months after treatment end. A treatment episode included consecutive prescription fills that occurred within 7 days from the end of the days' supply of the previous dispensing. Data were analyzed from March 1 to September 10, 2023.
MAIN OUTCOMES AND MEASURES
Treatment episodes were categorized by inferred indication using diagnoses preceding treatment initiation, including epilepsy, migraine or headache, mood disorders, and unknown or off-label uses. Pregnancy incidence rate ratios (IRRs) were calculated and were adjusted for age and calendar year. Contraceptive use (prescription contraceptives, intrauterine devices, and implants) during treatment was examined.
RESULTS
The cohort included 165 772 valproic acid treatment episodes among 69 390 women (mean [SD] age, 29.8 [10.0] years). Mood disorders (42.5%) were the most common indication, followed by migraine or headache (20.1%), with epilepsy playing a minor role (14.9%). Pregnancy incidence rates during valproic acid use remained unchanged, with a rate of 1.74 (95% CI, 1.14-2.53) per 100 person-years in 2005 and a rate of 1.90 (95% CI, 1.16-3.12) per 100 person-years in 2019. Compared with epilepsy, pregnancy rates were more than double for mood disorder (IRR, 2.16 [95% CI, 1.93-2.42]) and migraine or headache (IRR, 2.01 [95% CI, 1.92-2.09]). Few treatment episodes coincided with contraceptive use (37 012 [22.3%]), and oral dosage forms were the most common (27 069 [73.1%]).
CONCLUSIONS AND RELEVANCE
In this cohort study of patients of childbearing age who used valproic acid, pregnancy rates during valproic acid use did not decrease despite enhanced US Food and Drug Administration safety communications, and contraception use remained low. Patients with migraine and mood disorders accounted for the largest proportion of valproic acid use and had the highest pregnancy rates, while patients with epilepsy had the lowest. These findings suggest a need to enhance efforts to mitigate prenatal exposure to valproic acid, especially for indications where the risk of use during pregnancy outweighs the benefit.
Topics: Humans; Female; Valproic Acid; Pregnancy; Adult; Retrospective Studies; Adolescent; Prenatal Exposure Delayed Effects; Epilepsy; Young Adult; Anticonvulsants; Child; Pregnancy Rate; Mood Disorders; Migraine Disorders; United States
PubMed: 38776082
DOI: 10.1001/jamanetworkopen.2024.12680 -
Cellular and Molecular Neurobiology Oct 2021The lack of an effective pharmaceutical agent for spinal cord injury (SCI) is a current problematic situation for clinicians, as the rate of motor vehicle accidents... (Review)
Review
The lack of an effective pharmaceutical agent for spinal cord injury (SCI) is a current problematic situation for clinicians, as the rate of motor vehicle accidents among young adults is on the rise. SCI contributes to the high disability rate. Presently, evidences detailing the precise pathological mechanisms in SCI are limited, compounding to the unavailability of an effective treatment method. Surgery, though not a complete curative method, is useful in managing some of the associated symptoms of secondary SCI. Autophagy and inflammation are contributive factors to both exacerbation and improvement of SCI. The mammalian target of rapamycin (mTOR) signaling pathway is a key player in the regulation of inflammatory response and autophagy. Valproic acid (VPA), a clinically used antiepileptic drug, has been suggested to improve neurological conditions, including SCI. This report reviewed the correlation between mTOR and autophagy, as well as autophagy's role and the therapeutic effects of VPA in SCI. VPA regulates autophagy by potentially inhibiting mTORC1, a complex of mTOR, while also hindering inflammatory response. Conclusively, an effective treatment for SCI could lie in the timely regulation of mTOR signaling pathway, and VPA could be the potential drug that improves SCI owing to its propensity to regulate the mTOR signaling pathway.
Topics: Animals; Autophagy; Recovery of Function; Spinal Cord; Spinal Cord Injuries; TOR Serine-Threonine Kinases; Valproic Acid
PubMed: 32725456
DOI: 10.1007/s10571-020-00929-9 -
BMJ (Clinical Research Ed.) Apr 2018
Topics: Abnormalities, Drug-Induced; Anticonvulsants; Epilepsy; Female; Humans; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Valproic Acid
PubMed: 29669728
DOI: 10.1136/bmj.k1609 -
PloS One 2022The pharmacokinetics of valproic acid have been evaluated in a variety of populations however, the comparison in two different populations was yet to be reported. This...
PURPOSE
The pharmacokinetics of valproic acid have been evaluated in a variety of populations however, the comparison in two different populations was yet to be reported. This study is aimed to compare the pharmacokinetics of valproic acid in Pakistani and South Korean patients.
METHOD
The therapeutic drug monitoring (TDM) data of valproic acid from 92 Pakistani patients with 218 samples was combined with the data of 99 South Korean patients with 335 samples in order to form a pooled dataset of 191 patients with 553 samples. Population pharmacokinetic model was developed on NONMEM® software by using first order conditional estimation method for estimation of pharmacokinetic parameters. The influence of different covariates including ethnicity was evaluated the stepwise covariate modelling. The final model was evaluated for predictive performance and robustness by using goodness of fit plots and bootstrap analysis respectively.
RESULTS
The data was better described by one compartment model with first order elimination. The value for clearance (CL) of valproic in pooled data was 0.931 L/h with 43.4% interindividual variability (IIV) while volume of distribution (Vd) was 16.6 L with 22.3% IIV. In covariate analysis, ethnicity and body weight were significant covariates for CL while body weight was also significant for Vd.
CONCLUSION
A significant difference in CL of valproic acid among Pakistani and South Korean patients was observed. The model can be used for the dose tailoring of valproic acid based on ethnicity and body weight of Pakistani and South Korean patients.
Topics: Body Weight; Humans; Models, Biological; Pakistan; Republic of Korea; Valproic Acid
PubMed: 36001534
DOI: 10.1371/journal.pone.0272622