Podcasts about valproic

Valproic acid is one of the most frequently prescribed mood-stabilizing agents for bipolar disorder, and in some regions of the world, it now competes with lithium as the preferred treatment of choice for bipolar maintenance. There may soon be restrictions on the use of valproic acid, however, because of the risk in neural tube defects and major congenital malformations in children born to mothers and fathers who take it. In this podcast, Dr. Samuel Dotson, from the Northeast Georgia Health System in Gainesville, Georgia, and Emory University in Atlanta, and Dr. Andrew Nierenberg, from the Dauten Family Center for Bipolar Treatment Innovation at Massachusetts General Hospital and Harvard Medical School, discuss the current state of research regarding the benefits and risks of valproic acid in comparison to lithium use. They also discuss the importance of informing patients about their options, noting that lithium use has sometimes been perceived as riskier than it is. Dr. Dotson and Dr. Nierenberg are the authors of a Guest Editorial titled “Growing Concerns Over Valproate Teratogenicity Present an Opportunity for Lithium” in the March-April 2025 issue of The Journal of Clinical Psychopharmacology.

This episode is sponsored by Freed - Freed is an amazing time saver for busy healthcare professionals! It listens, transcribes, and writes medical notes for you! Go check them out and support our sponsor! In this episode, we highlight some of the most important clinical pearls (and highly testable pearls) on the following medications; Suboxone, lisdexamfetamine, nortriptyline, insulin lispro, and valproic acid. Suboxone is a combination of buprenorphine and naloxone used for opioid use disorder. Lisdexamfetamine is a stimulant medication that can be used to manage ADHD. Common side effects include weight loss, insomnia, hypertension, and tachycardia. Nortriptyline is a TCA medication known for its ability to cause anticholinergic side effects like constipation, dry eyes, dry mouth, urinary retention, and confusion. Insulin lispro is a rapid-acting insulin medication that is most often used to bring down post-prandial blood sugar. Valproic acid is an antiepileptic medication that can also be used for migraines.

Welcome to our next mood stabilizer episode, today we will be discussing Valproic Acid! Other medication names you may encounter: Depakote DR, ER, and Depakene. --- Support this podcast: https://podcasters.spotify.com/pod/show/psychrounds/support

This is the 26th podcast episode for the Psychiatric Medication Podcast Series. Series Description: Current literature indicates that podcasts can be an effective educational format to reach health professionals across the continuum of medical education, addressing a myriad of topics pertinent to providers. This episode serves as an overview of Valproic Acid/Depakote. This podcast season is the second released by East Carolina University's Office of Continuing Medical Education and may be beneficial for physicians, residents, fellows, nurse practitioners, physician assistants, and nurses. This podcast season is comprised of approximately 30 episodes, each focusing on different psychiatric medications for the non-psychiatric provider. Those tuning into the podcast's second season will receive a primer on the "bread and butter" behavioral health medications for primary care: antidepressants, antipsychotics, and mood stabilizers. Episodes will be released weekly on Wednesdays.Irene Pastis, MD & Daniel Majarwitz, MD

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.01.538959v1?rss=1 Authors: Dorsey, S. G., Mocci, E., Lane, M. V., Krueger, B. K. Abstract: There is an increased incidence of autism among the children of women who take the anti-epileptic, mood stabilizing drug, valproic acid (VPA) during pregnancy, moreover, exposure to VPA in utero causes autistic-like symptoms in rodents and non-human primates. Analysis of RNAseq data ob-tained from fetal mouse brains 3 hr after VPA administration revealed that VPA significantly [p(FDR) less than or equal to 0.025] increased or decreased the expression of approximately 7,300 genes. No significant sex dif-ferences in VPA-induced gene expression were observed. Expression of genes associated with neurodevelopmental disorders such as autism as well as neurogenesis, axon growth and synapto-genesis, GABAergic, glutaminergic and dopaminergic synaptic transmission, perineuronal nets, and circadian rhythms was dysregulated by VPA. Moreover, expression of 400 autism risk genes was significantly altered by VPA. In addition, expression of 247 genes that have been reported to play fundamental roles in the development of the nervous system, but are not linked to autism by GWAS, was significantly increased or decreased by VPA. The goal of this study was to identify mouse genes that are: (a) significantly up- or down-regulated by VPA in the fetal brain and (b) known to be associated with autism and/or to play a role in embryonic neurodevelopmental processes, perturbation of which has the potential to alter brain connectivity in the postnatal and adult brain. The set of genes meeting these criteria provides potential targets for future hypothesis-driven approaches to elucidating the proximal underlying causes of defective brain connectivity in neuro-developmental disorders such as autism. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Hyperammonemia is an adverse effect that poses clinical uncertainty regarding the prescription of valproic acid (VPA) use. The prevalence of symptomatic and asymptomatic hyperammonemia and its relationship to VPA concentration is not well established. In this podcast, clinical pharmacists Michelle Gnrya and Yiu-Ching Jennifer Wong of St. Paul's Hospital in Vancouver discuss their systematic review that summarizes evidence available regarding VPA-associated hyperammonemia and its prevalence, clinical outcomes, and management. Their review is published in the May-June 2023 issue of the Journal of Clinical Psychopharmacology. The review found various risk factors for this common adverse effect, including concomitant medications, liver injury, and defects in carnitine metabolism. With VPA discontinued, most symptomatic patients returned to baseline mental status with normalized ammonia level. Further studies are required to determine the benefit of routine ammonia level monitoring and to guide the management of VPA-associated hyperammonemia.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.11.536245v1?rss=1 Authors: Takla, T. N., Luo, J., Sudyk, R., Huang, J., Walker, J. C., Vora, N. L., Sexton, J. Z., Parent, J. M., Tidball, A. M. Abstract: Neural tube defects (NTDs) including anencephaly and spina bifida are common major malformations of fetal development resulting from incomplete closure of the neural tube. These conditions lead to either universal death (anencephaly) or life-long severe complications (spina bifida). Despite hundreds of genetic mouse models having neural tube defect phenotypes, the genetics of human NTDs are poorly understood. Furthermore, pharmaceuticals such as antiseizure medications have been found clinically to increase the risk of NTDs when administered during pregnancy. Therefore, a model that recapitulates human neurodevelopment would be of immense benefit to understand the genetics underlying NTDs and identify teratogenic mechanisms. Using our self-organizing single rosette spheroid (SOSRS) brain organoid system, we have developed a high-throughput image analysis pipeline for evaluating SOSRS structure for NTD-like phenotypes. Similar to small molecule inhibition of apical constriction, the antiseizure medication valproic acid (VPA), a known cause of NTDs, increases the apical lumen size and apical cell surface area in a dose-responsive manner. This expansion was mimicked by GSK3-{beta} and HDAC inhibitors; however, RNA sequencing suggests VPA does not inhibit GSK3-{beta} at these concentrations. Knockout of SHROOM3, a well-known NTD-related gene, also caused expansion of the lumen as well as reduced f-actin polarization. The increased lumen sizes were caused by reduced cell apical constriction suggesting that impingement of this process is a shared mechanism for VPA treatment and SHROOM3-KO, two well-known causes of NTDs. Our system allows the rapid identification of NTD-like phenotypes for both compounds and genetic variants and should prove useful for understanding specific NTD mechanisms and predicting drug teratogenicity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.24.513470v1?rss=1 Authors: Maisterrena, A., de Chaumont, F., Longueville, J.-E., Balado, E., Ey, E., Jaber, M. Abstract: Autism Spectrum Disorder (ASD) is a progressive neurodevelopmental disorder characterized mainly by deficits in social communication and stereotyped and restricted interests. Deficits in social interactions in ASD animal models are generally analysed using the three chambers test paradigm that is simple to implement and use but fails to detect subtle social deficits or complex social behavior on an extended period of time within a group of mice. Here, we set up a novel procedure entitled the Live Mouse Tracker (LMT) that detects a great number of complex social behaviours that we recorded continuously for up to three days in groups of 4 mice. This was performed in the valproic acid (VPA) mouse model where VPA (450 mg/kg) was injected to pregnant females at E12.5. Studies were performed with a special focus on females given that ASD is 3-4 times more diagnosed in males than in females and that several ASD models failed to detect major social deficits in females, contrary to males. Comparisons were made within groups of 4 female animals with same treatment or within groups of different treatments (saline versus VPA). We report that VPA females show several types of social deficits and that are different in nature and magnitude in relation with time (from 1 hour to 3 days). These deficits were also different when VPA mice were tested together compared to when they were mixed with saline treated mice. Indeed, while social behavior was improved in VPA mice with the presence of saline mice while that of saline mice was negatively affected by the presence of VPA mice. This study indicates that female VPA mice show several social deficits, contrary to the common knowledge. It further implies that ASD related behavior alters normal behavior in a mixed group of mice. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

References Dr Guerra's lipid lecture notes European Medicines Agency•20/05/2022 Pharmaceuticals (Basel). 2022 Feb; 15(2): 192 NeuropharmacologyVolume 128, January 2018, Pages 54-62 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

In this episode we cover the obvious, and subtleties around Valproic Acid toxicities. We talk everything from cerebral edema, giving that L-Carnitine and when to spin that IHD machine. 

This episode covers valproic acid!

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.29.220350v1?rss=1 Authors: Bass, J. S., Tuo, A., Ton, L., Jankovic, M., Kapadia, P. P., Schirmer, C., Krishnan, V. Abstract: Objective: Antiepileptic drugs (AEDs) require daily ingestion for maximal seizure prophylaxis. Adverse psychiatric consequences of AEDs present as: (i) reversible changes in mood, anger, anxiety and/or irritability that often necessitate drug discontinuation, and (ii) autism and/or cognitive/psychomotor developmental delays following fetal exposure. Technical advances in quantifying naturalistic rodent behaviors may provide sensitive preclinical estimates of AED psychiatric tolerability and neuropsychiatric teratogenicity. Methods: Using instrumented home-cage monitoring, we assessed how valproic acid (VPA, dissolved in sweetened drinking water) alters home-cage behavior in adult C57BL/6J mice and in the adult offspring of VPA-exposed breeder pairs. By utilizing a pup open field assay, we also examined how prenatal VPA exposure impacts early spontaneous exploratory behavior. Results: At 500-600mg/kg/d, chronic VPA produced hyperphagia and increased wheel-running without impacting sleep, activity and measures of risk aversion. When applied chronically to breeder pairs of mice, VPA prolonged the latency to viable litters without affecting litter size. Two-week old VPA-exposed pups displayed open field hypoactivity without alterations in thigmotaxis. As adults, prenatal VPA-exposed mice displayed active state fragmentation, hypophagia and increased wheel running, together with subtle alterations in home-cage dyadic behavior. Interpretation: Through automated home-cage assessments of C57BL/6J mice, we capture an ethologically centered psychopharmacological profile of enterally administered VPA that is aligned with human clinical experience. By characterizing the effects of pangestational VPA exposure, we discover novel murine expressions of pervasive neurodevelopment. Incorporating rigorous comprehensive assessments of neuropsychiatric tolerability may inform the design of future AEDs with improved neuropsychiatric safety profiles, both for patients and their offspring. Copy rights belong to original authors. Visit the link for more info

Thank you to Cam Mecham, OM III from RVU, St. George Campus and Jed Roundy, student at Utah State University for participating in this discussion. This podcast is judged to be of moderate value in shelf exam prep for the 3rd year psychiatry rotation.

In this episode, David Puder, M.D. and Michael Cummings, M.D. discuss the history, uses, and side effects of Valproic Acid which is a mood stabilizer for various conditions including: Bipolar Disorder, Schizophrenia, and Borderline Personality Disorder. 

We discuss how Valproic Acid improves gross motor function, but not respiratory function in SMA patients. Also, Community Development Manager Kevin Schaefer introduces a forum dedicated to Zolgensma, a gene therapy designed to treat SMA. Are you interested in understanding gene therapy? ExploreGeneTherapy.com has helpful information about gene therapy, including its history and how it is being investigated for the treatment of genetic diseases. Visit www.exploregenetherapy.com

Valproate (valproic acid, Depakote) has numerous uses which includes migraines, seizures, and bipolar disorder. In a patient who is taking valproate, it is important to monitor for signs and symptoms of confusion as this drug can cause elevated ammonia levels. When switching between dosage forms of valproate, you must recognize that the bioavailability is not the same between each different dosage form. This could lead to toxicity or treatment failure. Valproic acid has a boxed warning for hepatotoxicity and liver function needs to be monitored. Valproic acid can increase lamotrigine levels which ultimately could lead to an increased risk of lamotrigine induced SJS.

Dr Paul Wang:                   Welcome to the monthly podcast "On the Beat" for Circulation: Arrhythmia, and Electrophysiology. I'm Dr Paul Wang, Editor-in Chief, with some of the key highlights from this month's issue.                                                 In our first manuscript, Marie Bayer Elming and associates, examined whether the right ventricular ejection fraction can identify patients with non-ischemic systolic heart failure, more likely to benefit from ICD implantation. The Danish study, to assess the efficacy of ICDs in patients with non-ischemic systolic heart failure, on mortality, the Danish study, randomized patients with non-ischemic systolic heart failure to ICD our control. In 239 patients with interpretable cardiovascular magnetic resonance images, the right ventricular volume and ejection fraction was measured. Right ventricular ejection fraction was an independent predictor of all-cause mortality, with a hazard ration 1.34 per 10% absolute decrease in our right ventricular ejection fraction. P=0.02. There is statistically significant interaction between right ventricular ejection fraction and the effect of ICD implantation. P=0.001. ICD implantation significantly reduced all-cause mortality in patients with right ventricular systolic dysfunction. Hazard ratio 0.41, but not in patients without right ventricular systolic dysfunction.                                                 Thus, in this post-hoc analysis of the Danish trial, ICD therapy was associated with survival benefit in patients with bi-ventricular heart failure.                                                 In our next paper, Dawn Pedrotty and Volodymyr Kuzmenko and associates, have proposed a concept of using a stretchable, flexible, bio patch, with conductive properties, to attempt to restore conduction across regions in which activation is disrupted. They use carbon nanotube patches, composed of nanofibrillated cellulose, in single wall carbon nanotube ink, 3-D printed in conductive patterns onto bacterial nanocellulose.                                                 Electro anatomic mapping was performed on normal epicardium and repeated over surgically disruptive epicardium, and finally with the patch applied passively. The patch resulted in restored conduction based on mapping.                                                 In our next paper, Ayman Hussein and colleagues developed a fully automated platform to collect patient reported outcomes in a prospective cohort of atrial fibrillation ablation. Two thousand one hundred and seventy-five patients were eligible to receive 10,903 patient reported outcome assessment invitations. More follow up assessments were obtained with automated patient reported outcomes in routine follow-up, compared with routine follow up alone, P > 0.001, which allowed for longer duration of follow up, 378 vs 217 days. By automated patient reported outcomes, a large number of disease specific variables were collected and showed improvement in quality of life. Baseline median AF symptom severity score of 12 and ranged between 2 and 3 on subsequent assessments, P > 0.0001. This improvement was also true for each of the atrial fibrillation symptom severity score components. In patient reported outcomes, there was a significant reduction in atrial fibrillation burden, such as frequency and duration episodes and associated healthcare utilization including emergency visits and hospitalizations after the ablation procedures.                                                 In our next paper, Nicolas Johner, Dipen Shah, and associates, examined the role of post pacing intervals shorter than tachycardia cycling during entrainment mapping. The author studied 24 non-cavotricuspid isthmus dependent macro oriented atrial flutters in 19 consecutive patients. High density electro anatomic activation maps were acquired with a 64-electrode basket catheter of 102 entrainment mapping sites. Post pacing interval difference less than 30 was observed at 72 sites on complete maps of 24 atypical atrial flutters compared to sites with the difference in post pacing intervals 0 to 30, with 45 sites difference in the post pacing interval less than 0 at 27 were more commonly located within isthmuses less than 15mm wide and more frequently located in within 5mm of the leading wave front. It also exhibited slower local conduction, lower voltages in more frequently fractioned electrograms. The authors concluded that in atrial flutter, sites with differences with the post pacing interval are markers of limited width critical isthmuses with slower conduction velocity, while sites with difference in post pacing interval 0 to 30ms are often not in close proximity to the reentrance circuit. Virtual electrode simultaneous down and up stream, antidromic capture of a confined isthmus of slow conduction can explain a difference in the post pacing interval less than 0.                                                 In the next paper, José Manuel Alfonso-Almazán, and associates studied the safety and efficacy parameters associated with catheter-based radiofrequency delivery at the root of the aorta and pulmonary artery. The author studied 34 pigs undergoing in vivo catheter based ablation using continuous contact force and lesion index monitoring during 60 second radiofrequency delivery with an open, irrigated tip catheter. Twenty-eight animals were allocated to groups receiving 40 watts, 50 watts, or 60 watts and acute, chronic arterial damage was quantified by multi photon microscopy in ex vivo samples. Adjacent microlesion were quantified in parallel samples. The remaining 8 pigs, these were used to validate safety and efficacy parameters. Acute collagen elastic alterations were significantly associated with radiofrequency power, although chronic assessment revealed vascular wall recovery in patients without [steam pop 00:06:56]. The main parameters associated with steam pops were median peak temperature greater than 42C, and impedance falls greater than 23 ohms. Unlike other parameters, lesion index values of 9.1 units were associated with the presence of adjacent myocardial lesions in both univariate and multivariate analyses. In the validation group, lesion index values using 40 watts over a range of contact forces correlated with the size of radiofrequency lesions. Lesion index values obtained during 40 watts radiofrequency application reliably monitor safe and effective lesion creation at the root of the great arteries.                                                 In our next paper, Eiichiro Oka and associates examine the prevalence and significance of the early repolarization electrocardiographic pattern and its mechanistic insight based on cardiac magnetic resonance findings in patients with acute myocarditis. The author studied 30 patients with the diagnosis of acute myocarditis. Nine had an early repolarization electrocardiographical pattern, which was defined as a terminal QRS notching or slurring with an amplitude of greater than zero-point millivolts in at least two inferior and/or lateral leads. The early repolarization group, while the remaining 21 cases had broad ST elevation or pathological QAs.                                                 The non-early repolarization group. The cardiac prepotency level was significantly higher in the non-early repolarization group than the early repolarization group. The ECD changes returned to baseline, along with a normalization of the cardiac biomarkers. Nine of the 21 non-early repolarization group patients, but none of the 9 early repolarization groups developed fulminant course of lethal ventricular arrhythmias. T2-weighted cardiac magnetic resonance imaging showed high intensity signals over the entire transmittal left vertical in the non-early repolarization group, where as they were localized to the left ventricle epicardium in early repolarization group. The early repolarization pattern in acute myocarditis was transient and reversible, and was not associated with a worse prognosis. Inflammation or swelling localized to the left ventricular epicardium, due to myocarditis, may provide a mechanistic insight into the early repolarization pattern.                                                 In our next paper, Beatrix Scholz and Jan Sebastian Schulte and associates analyzed whether the histone deacetylase class I and II inhibitor valproic acid is able to attenuate atrial remodeling in CREM-IbΔCx (TG) transgenic mice. A mouse model of extensive atrial remodeling with age dependent progression from spontaneous atrial ectopy to paroxysmal and finally long lasting atrial fibrillation. Valproic acid was administered for 7 or 25 weeks to transgenic and control mice. Valproic acid attenuated many components of atrial remodeling that were present in the transgenic mice.                                                 Valproic acid significantly reduced atrial dilation, cardiomyocyte enlargement, atrial fibrosis, and the disorganization of myocytes ultrastructure. It significantly reduced the occurrence of atrial thrombi, reversed action potential alterations, and finally delayed the onset of atrial fibrillation by 4 to 8 weeks. Increased histone H4 acetylation in atria from valproic acid treated transgenic mice verified effective in in vivo histone deacetylase inhibition. Cardiomyocyte specific genetic inactivation of histone deacetylase HDAC 2 in transgenic mice attenuated the ultrastructural disorganization of myocytes compared to valproic acid. The author suggests that valproic acid, clinically available, well tolerated, and prescribed to many patients for years, has a therapeutic potential to delay the development of atrial remodeling in the onset of atrial fibrillation in patients at risk.                                                 In our next paper, Bence Hegyi and associates measure the major inward currents in their calcium channel and beta-adrenergic dependence under physiologic action potential clamp in rabbit ventricular myocytes in chronic pressure volume overload induced heart failure versus age matched controls. They found that CAM kinase II dependent up regulation of late sodium current in heart failure significantly contributes to the action potential prolongation in increased short-term variability of action potential repolarization, which may lead to increased arrhythmia propensity and is further exacerbated by adrenergic stress.                                                 In a research letter, Arnaud Bisson and associates examined mitral regurgitation in 838, or 10%, of 8675 patients with atrial fibrillation. A total 135, or 16%, had severe mitral regurgitation. During mean follow-up with 2.5 years, 688 ischemic stroke or thromboembolic events were recorded. mitral regurgitation was associated with a non-significant higher risk of these embolic events. After adjustment for anticoagulant and antiplatelet use, CHA2DS2-VASc and HAS-BLED scores, patients with mitral regurgitation tended to have a higher all cause or cardiovascular mortality but had similar risks of ischemic stroke or thromboembolic events, when compared to patients with no mitral regurgitation. Severe mitral regurgitation was also associated with similar risk for ischemic stroke and thromboembolic events when compared with other atrial fibrillation patients. However, our findings indicate that in patients with atrial fibrillation, neither mitral regurgitation nor severe mitral regurgitation, appears to independently be associated with a different risk of ischemic stroke or thromboembolic events. The perceived protective effect of mitral regurgitation against the risk of thromboembolic events is not relevant in atrial fibrillation when using a contemporary risk score scheme, the CHA2DS2-VASc score.                                                 In our final research paper, Jack Z. Li and associates noted that in 2017, an aggregate of four manufacturers of devices yielded 89.6% with the DF-4 ICD implants. While DF-4 and DF-1 leads generally have comparable performance, several concerns over reduced versatility of the DF-4 have been raised. First, to downgrade an ICD with a DF-4 lead to a pacemaker, a generator change, a new right ventricular pace sense lead must be implanted. The DF-4 pin is incompatible with the IS-1 port and there is no straightforward way to bridge this gap. In contrast, the DF-1 IS-1 lead requires only capping of the DF-1 pin. Second, if an ICD with DF-4 lead has either a distal coil or a right ventricular pacing malfunction, a new lead must be implanted. Third, if a ICD with DF-4 lead has a high defibrillation threshold, management requires either a new DF-1 IS-1 lead with an adapter for a subcutaneous array, or an adapter that inserts into the DF-4 port and receives both the DF-4 lead and the DF-1 pin of the subcutaneous lead. Physicians should have the foresight to select DF-1 leads at the time of initial implant in selected circumstances, such as high possibility for elevated defibrillation threshold requiring a subcutaneous lead or array.                                                 That's it for this month! We hope that you'll find the journal to be the go-to place for everyone interested in the field. See ya next time.                                                 This program is copyright American Heart Association 2019.

Valproic acid combined with L-carnitine for effective in treating SMA: https://smanewstoday.com/2017/09/07/valproic-acid-fails-to-improve-survival-of-sma-type-i-infants-in-carnival-clinical-trial/

This week, I talk about the chain of events that lead to the serendipitous discovery of valproic acid. Valproic acid is one of the key ingredients in Depakote, the most widely prescribed antiepileptic (seizure-controlling) drug in the world. I introduced the topic by talking about a recent lawsuit against Abbott Laboratories, the company that makes Depakote, for illegally marketing their product...