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Handbook of Clinical Neurology 2023Though clearly described as far back as the 17th century, chronic migraine has defied precise categorization and has continued to develop as an important diagnostic...
Though clearly described as far back as the 17th century, chronic migraine has defied precise categorization and has continued to develop as an important diagnostic concept with significant societal impact. Worldwide prevalence is estimated to be between 1% and 3%, and these patients form a dynamic group cycling between chronic and episodic migraine. Theories of pathogenesis are developing supported by recent imaging and other findings. Of the many determinants of progression to chronic migraine, overuse of acute abortive headache medications may be one of the most important modifiable factors. Treatment strategies, in addition to educational measures, have included various preventive migraine medications such as topiramate, valproate, and onabotulinumtoxinA. CGRP monoclonal antibodies are efficacious for the management of chronic migraine both with and without medication overuse.
Topics: Humans; Migraine Disorders; Prescription Drug Overuse; Valproic Acid
PubMed: 38043961
DOI: 10.1016/B978-0-12-823356-6.00008-1 -
The Journal of Trauma and Acute Care... Aug 2020The leading causes of death in military conflicts continue to be hemorrhagic shock (HS) and traumatic brain injury (TBI). Most of the mortality is a result of patients... (Review)
Review
The leading causes of death in military conflicts continue to be hemorrhagic shock (HS) and traumatic brain injury (TBI). Most of the mortality is a result of patients not surviving long enough to obtain surgical care. As a result, there is a significant unmet need for a therapy that stimulates a "prosurvival phenotype" that counteracts the cellular pathophysiology of HS and TBI to prolong survival. Valproic acid (VPA), a well-established antiepileptic therapy for more than 50 years, has shown potential as one such prosurvival therapy. This review details how VPA's role as a nonselective histone deacetylase inhibitor induces cellular changes that promote survival and decrease cellular pathways that lead to cell death. The review comprehensively covers more than two decades worth of studies ranging from preclinical (mice, swine) to recent human clinical trials of the use of VPA in HS and TBI. Furthermore, it details the different mechanisms in which VPA alters gene expression, induces cytoprotective changes, attenuates platelet dysfunction, provides neuroprotection, and enhances survival in HS and TBI. Valproic acid shows real promise as a therapy that can induce the prosurvival phenotype in those injured during military conflict.
Topics: Animals; Armed Conflicts; Brain Injuries, Traumatic; Gene Expression; Histone Deacetylase Inhibitors; Humans; Kaplan-Meier Estimate; Military Medicine; Military Personnel; Resuscitation; Shock, Hemorrhagic; Valproic Acid; War-Related Injuries
PubMed: 32282756
DOI: 10.1097/TA.0000000000002721 -
Journal of Pharmacological Sciences May 2020Valproic acid is a commonly used drug for many psychiatric disorders, particularly for epilepsy. However, it has been reported that its use is associated with possible...
Valproic acid is a commonly used drug for many psychiatric disorders, particularly for epilepsy. However, it has been reported that its use is associated with possible side effects including hepatotoxicity. The present study investigated the hepatoprotective effect of ellagic acid against valproic acid-induced hepatotoxicity in rats. Ellagic acid (60 mg/kg/day; p.o) was treated for one week, followed by concomitant injection of valproic acid (250 mg/kg/day; i.p.) for another 14 consecutive days to induce hepatocellular damage in adult Sprague-Dawley rats. Valproic acid showed a marked increase in serum enzyme activities, AST, ALT, ALP and GGT. In addition, it significantly increased MDA and NO along with a marked decline in reduced GSH content. At the same time, valproic acid administration resulted in marked elevation in hydroxyproline, TNF-α production and NF-kB expression. These results were confirmed by histopathological examination. Treatment with ellagic acid markedly attenuated valproic acid-induced hepatic injury in rats.
Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Ellagic Acid; Glutathione; Liver; Male; Nitric Oxide; Oxidative Stress; Phytotherapy; Rats, Sprague-Dawley; Valproic Acid
PubMed: 32139333
DOI: 10.1016/j.jphs.2020.01.007 -
Journal of the College of Physicians... Sep 2021To determine the frequency of hyperglycinemia in epileptic patients taking valproic acid (VPA); and the correlation between therapeutic dose of valproic acid and plasma... (Observational Study)
Observational Study
OBJECTIVES
To determine the frequency of hyperglycinemia in epileptic patients taking valproic acid (VPA); and the correlation between therapeutic dose of valproic acid and plasma glycine levels in epileptic patients.
STUDY DESIGN
Observational, cross-sectional study.
PLACE AND DURATION OF STUDY
Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology Rawalpindi, in collaboration with Combined Military Hospital, Rawalpindi, from August 2020 to January 2021.
METHODOLOGY
Plasma glycine levels were analysed on ion exchange chromatography (IEC)-based instrument, Biochrome 30+ of epileptic patients undergoing treatment with anti-epileptic agents. Therapeutic doses of valproic acid were taken as serum trough levels of valproic acid and analysed on chemiluminescence-based Abbott Architect Plus i1000 SR. Mann-Whitney U-test was applied to compare plasma glycine levels in epileptic patients on valproic acid and those on multiple anti-epileptic agents. Spearman's correlation was used to correlate plasma glycine levels in epileptic patients with trough levels of valproic acid, duration of treatment and frequency of fits/year.
RESULTS
A total of 77 participants, upto 15 years of age, were enrolled. Plasma glycine levels were significantly raised (p <0.001) in those epileptics who were on valproic acid (monodrug therapy), in comparison with those on multiple anti-epileptic agents. There were significant positive correlations between glycine levels and trough valproic acid levels (r = 0.830), duration of treatment (r = 0.525) and frequency of seizures (r = 0.326).
CONCLUSION
Epileptic patients treated with valproic acid (VPA) had raised plasma glycine levels, that increased with therapeutic dose of valproic acid and duration of treatment and was associated with increased frequency of fits in those patients. Key Words: Epilepsy, Seizure, Glycine, Valproic acid.
Topics: Anticonvulsants; Cross-Sectional Studies; Epilepsy; Glycine; Humans; Valproic Acid
PubMed: 34500514
DOI: 10.29271/jcpsp.2021.09.1020 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2017The article summarizes domestic and international studies on the development and clinical investigation of valproates including multiple studies of a research team... (Review)
Review
The article summarizes domestic and international studies on the development and clinical investigation of valproates including multiple studies of a research team directed by the author. Valproate targets are considered in biological and clinical aspects. A spectrum of action and advantages of the brand drug (depakine) compared to generics and other antiepileptic drugs are discussed. A number of recommendations for practitioners about using valproates are proposed.
Topics: Anticonvulsants; Drugs, Generic; Epilepsy; GABA Agents; Humans; Russia; Valproic Acid
PubMed: 29265098
DOI: 10.17116/jnevro2017117111129-134 -
Pakistan Journal of Pharmaceutical... Jul 2018The unpredictable and unfavorable connection of dose and plasma concentration of valproic acid supports the necessity to regularly measure its plasma concentration. The... (Clinical Trial)
Clinical Trial
The unpredictable and unfavorable connection of dose and plasma concentration of valproic acid supports the necessity to regularly measure its plasma concentration. The present study is drug monitoring of valproic acid and comparative evaluation of therapeutic monitoring results of valproic acid for assessment of clinical response, safety and toxicity in different age and gender groups of Chinese epileptic patients. This knowledge will help the clinicians in adjusting the drug dosages of valproic acid in various sub-groups of epileptic patients for enhancing the safety and minimizing the toxicity of valproic acid. A total of 206 plasma samples (126 males and 80 females) of epileptic patients using valproic acid were requested for therapeutic drug monitoring by neurology department of Qilu Hospital. It was found that 29 % of the total samples were found in sub-therapeutic levels, 13% of the samples had toxic levels and 58% of all the samples had valproic acid levels in therapeutic range. The difference in plasma concentration of valproic acid is notably altered in gender and various age groups. However, this requires further investigation. Despite the majority of samples in the therapeutic range, there was an unfavorable clinical response. The outcomes of the current research work exposed that there was a poor correlation between the plasma concentration and clinical response. Careful attention must be applied to specific gender and particular age group on an individual basis in the interpretation of plasma concentration results, in order to facilitate the modification of doses and develop the best approach in treatment and to obtain the desired clinical response because multiple factors can affect the valproic acid plasma concentration. Through these results, it can be concluded that poor correlation exists between valproic acid plasma concentration and clinical response.
Topics: Adult; Age Factors; Aged; Anticonvulsants; Child, Preschool; Drug Monitoring; Epilepsy; Female; Humans; Infant; Male; Sex Factors; Treatment Outcome; Valproic Acid
PubMed: 30203778
DOI: No ID Found -
The Journal of Neuroscience Nursing :... Feb 2017Valproic acid (VPA) is a medication used to treat multiple neuroscience conditions. It is an inexpensive and useful medication, with a low incidence of adverse drug...
Valproic acid (VPA) is a medication used to treat multiple neuroscience conditions. It is an inexpensive and useful medication, with a low incidence of adverse drug events. Nonetheless, optimal clinical outcomes require that a series of screening and laboratory steps be followed before the initiation of VPA therapy. An additional aspect of pharmacovigilance is to recognize clinical patterns signaling genetic traits that preclude VPA, background of the black box warnings, targeted assessments, and laboratory monitoring indicated while on VPA. The intention of this article is to provide a focused summary of published information clinically relevant to prescribing and monitoring these patients.
Topics: Anticonvulsants; Drug Monitoring; Humans; Mutation; Neuroscience Nursing; Polypharmacy; Valproic Acid
PubMed: 28060221
DOI: 10.1097/JNN.0000000000000259 -
Biomedicine & Pharmacotherapy =... May 2021Autism spectrum disorder (ASD) is a sort of mental disorder marked by deficits in cognitive and communication abilities. To date no effective cure for this pernicious... (Review)
Review
Autism spectrum disorder (ASD) is a sort of mental disorder marked by deficits in cognitive and communication abilities. To date no effective cure for this pernicious disease has been available. Valproic acid (VPA) is a broad-spectrum, antiepileptic drug, and it is also a potent teratogen. Epidemiological studies have shown that children exposed to VPA are at higher risk for ASD during the first trimester of their gestational development. Several animal and human studies have demonstrated important behavioral impairments and morphological changes in the brain following VPA treatment. However, the mechanism of VPA exposure-induced ASD remains unclear. Several factors are involved in the pathological phase of ASD, including aberrant excitation/inhibition of synaptic transmission, neuroinflammation, diminished neurogenesis, oxidative stress, etc. In this review, we aim to outline the current knowledge of the critical pathophysiological mechanisms underlying VPA exposure-induced ASD. This review will give insight toward understanding the complex nature of VPA-induced neuronal toxicity and exploring a new path toward the development of novel pharmacological treatment against ASD.
Topics: Animals; Anticonvulsants; Autism Spectrum Disorder; Female; Humans; Neurotoxicity Syndromes; Pregnancy; Prenatal Exposure Delayed Effects; Valproic Acid
PubMed: 33761592
DOI: 10.1016/j.biopha.2021.111322 -
The Journal of Emergency Medicine Nov 2022Valproic acid (VPA) is a common antiepileptic drug that is also used routinely for various psychiatric disorders. VPA toxicity typically manifests as central nervous... (Review)
Review
BACKGROUND
Valproic acid (VPA) is a common antiepileptic drug that is also used routinely for various psychiatric disorders. VPA toxicity typically manifests as central nervous system depression, while hyperammonemic encephalopathy and hepatotoxicity are potentially life-threatening complications.
CASE REPORT
We describe the case of a 56-year-old man who presented to the emergency department after an intentional VPA overdose, was found to have hyperammonemia, and was treated with L-carnitine exclusively. He was subsequently admitted to the hospital for monitoring and serial laboratory testing. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although VPA toxicity has conventionally been managed by gastric decontamination, L-carnitine, and, in severe and refractory cases, extracorporeal removal, recent literature supports the use of carbapenem antibiotics, particularly meropenem. Thus, we report the details of current treatment modalities for VPA toxicity by reviewing current literature.
Topics: Male; Humans; Middle Aged; Valproic Acid; Anticonvulsants; Hyperammonemia; Drug Overdose; Carnitine
PubMed: 36229318
DOI: 10.1016/j.jemermed.2022.07.009 -
Archives of Gerontology and Geriatrics 2020The neuroprotective effect of valproic acid has been observed in the animal models of neurodegeneration, which suggests it as a potential candidate for clinical trials.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The neuroprotective effect of valproic acid has been observed in the animal models of neurodegeneration, which suggests it as a potential candidate for clinical trials. In this paper, we aimed to systematically analyze the efficacy and safety of valproic acid in the treatment of dementia.
METHODS
We searched the electronic databases PubMed, EMBASE, CINAHL, Cochrane Library and China National Knowledge Infrastructure until March 2020 for the eligible randomized controlled trials, as well as the unpublished and ongoing trials. We pooled the results using a random-effects model.
RESULTS
We included seven studies with 770 randomized patients with dementia, which compared valproic acid with placebo. Indeed, there were no significant differences found in the scores of Mini-mental State Examination, Cohen-Mansfield Agitation Inventory and number of patients with adverse events. Valproic acid is generally well-tolerated in patients with dementia, even in long-term therapy for 24 months.
CONCLUSION
Insufficient evidences are found to support valproic acid in the treatment of dementia for cognitive, psychiatric symptoms or disease-modifying. The anticipations for a success in the trial of valproic acid for dementia in the future look not optimistic based on the available evidence.
Topics: Dementia; Enzyme Inhibitors; Humans; Psychomotor Agitation; Valproic Acid
PubMed: 32413690
DOI: 10.1016/j.archger.2020.104091