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INTRODUCTION: Sodium valproate is one of the most important antiepileptic drugs. It can be effective as a preventive treatment for migraine, it has also found use in the maintenance treatment of bipolar disorder and acute mania,it is sometimes used in the treatment of chronic neuropathic pain and fibromyalgia, in the treatment of schizophrenia borderline personality disorder and acquired brain injury, this drug is used off-label. Its overdose can be fatal. MATERIALS AND METHOD: Patient information was collected from hospital records available in the clinical toxicology department. In addition, we conducted a literature review on sodium valproate treatment, its toxicity, side effects and pharmacokinetics using PubMed. CASE REPORT: A 57-year-old patient with a history of depressive disorders was admitted to the Clinical Department of Toxicology and Cardiology in Lublin for intentional intoxication with the drug Absenor (sodium valproate). The patient had taken 3 packages of Absenor 500 mg (300 tablets in total) for suicidal purposes. The determined concentration of valproic acid was 841 µg/ml, and the patient's condition was very severe. Despite the treatment administered-multiple attempts at gastric lavage, administration of activated charcoal, performance of hemodialysis procedures, administration of infusion of catecholamines, the patient died on the fifth day of hospitalization. CONCLUSION: An overdose of sodium valproate can be fatal. Keep this in mind when ordering this drug for patients with a positive history of suicide attempts.

This study aimed to investigate the potential role of gut microbiota in the hepatotoxicity of sodium valproate (SVP) and the protective effect of ginsenoside compound K (G-CK) administration against SVP-induced hepatotoxicity in rats. Measurements of 16S rRNA showed that SVP supplementation led to a 140.749- and 248.900-fold increase in the relative abundance of Akkermansia muciniphila (A. muciniphila) and Bifidobacterium pseudolongum (B. pseudolongum), respectively (p < 0.05). The increase in A. muciniphila was almost completely reversed by G-CK treatment. The relative abundance of A. muciniphila was strongly positively correlated with aspartate transaminase (AST) and alanine aminotransferase (ALT) levels (r > 0.78, p < 0.05). The PICRUSt analysis showed that G-CK could inhibit the changes of seven pathways caused by SVP, of which four pathways, including the fatty acid biosynthesis, lipid biosynthesis, glycolysis/gluconeogenesis, and pyruvate metabolism, were found to be negatively correlated with AST and ALT levels (r ≥ 0.70, p < 0.01 or < 0.05). In addition, the glycolysis/gluconeogenesis and pyruvate metabolism were negatively correlated with the relative abundance of A. muciniphila (r > 0.65, p < 0.01 or < 0.05). This alteration of the gut microbiota composition that resulted in observed changes to the glycolysis/gluconeogenesis and pyruvate metabolism may be involved in both the hepatotoxicity of SVP and the protective effect of G-CK administration against SVP-induced hepatotoxicity. Our study provides new evidence linking the gut microbiota with SVP-induced hepatotoxicity.

Background: Fanconi syndrome (FS) can be of primary or secondary origin. Some cases of FS secondary to the use of sodium valproate (VPA) have been described, mostly in children with severe psychomotor retardation who are fed by feeding device. The objetive of this study was to describe patients treated for this entity in our center, comparing them against the published literature.Methods: Descriptive study of our patients and those found in the literature. Epidemiologic and clinical data were collected.Results: We describe seven patients (three to 17 years old) with severe psychomotor retardation and undergoing treatment with VPA. Four presented pathologic fractures before the diagnosis of FS, and in three patients the diagnosis was reached due to abnormal laboratory findings. A review of the published cases was carried out and, including our sample, a total of 42 patients were studied: 51.3% were male, and the median age at diagnosis of FS was 6 years. Severe psychomotor retardation was found in 92.8% of patients, 78% carried a feeding device, and 77.5% received treatment with several antiepileptic drugs. The mean duration of VPA treatment was 5.7 years (range 2 to 7.5 years). Fifteen patients (37.5%) had bone complications. The resolution time of FS after discontinuation of drug therapy ranged from two to 19 months (median 4 months).Conclusions: FS related to VPA is a rare complication, but it should be considered in patients with epilepsy, especially if they have severe psychomotor retardation, are users of feeding devices, and receive other antiepileptic treatments in addition to VPA. [ABSTRACT FROM AUTHOR]

Objective: Sodium valproate and ibuprofen are drugs with known efficacy in the treatment of headache associated with acute migraine attacks. In this study, our aim was to compare the efficacy of these two drugs in the treatment of acute migraine attacks when administered as a single intravenous (IV) dose in the emergency department.Materials and Method: This study was designed as a prospective, randomized controlled, double-blinded study and included patients aged 18 to 65 years who presented to the emergency department with acute headache and met the criteria of 'migraine without aura' according to the International Classification of Headache Disorders. The patients were randomized into two groups and given a single dose of 800 mg sodium valproate or 800 mg ibuprofen in 150 mL of normal saline by IV infusion over five minutes. Changes in pain levels were assessed using the Numerical Rating Scale (NRS) for pain over a two-hour period.Results: Ninety-nine patients (49 patients in the sodium valproate group and 50 in the ibuprofen group) completed the trial, and their data were included in the statistical analysis. The mean decrease in the post-treatment delta NRS values was statistically significantly higher in the sodium valproate group than in the ibuprofen group. The mean differences were 1.69 [confidence interval (CI): 1.02-2.37, p<0.001], the mean difference between N0 and N2 was 3.61 (CI: 2.96-4.26, p < 0.001), the mean difference between N0 and N3 was 4.11 (CI: 3.54-4.67, p < 0.001), and the mean difference between N0 and N4 was 3.92 (CI: 3.67-4.46, p < 0.001). The number of patients who achieved the primary endpoint of pain relief was significantly higher in the sodium valproate group than in the ibuprofen group (p < 0.001). According to the Kaplan-Meier analysis showing the rates of reaching the targeted endpoint, there was a significant difference in the efficacy of the two-treatment group (χ2 = 79.98, CI: 80.35-99.65; p = 0.000). [ABSTRACT FROM AUTHOR]

Chronic headache disorders can cause substantial disability and be treatment refractory. Often, these patients are excluded from clinical trials with leaving little evidence to guide treatment. In adults, divalproex sodium is an effective preventive migraine treatment. All pediatric patients admitted for first-time sodium valproate infusions to treat refractory, chronic migraine (CM), new daily persistent headache, or persistent headache attributed to head trauma from January 2017 to October 2020 were identified for review. Each patient underwent a standardized, 4-day protocol. A new preventive was started one week after discharge. Data on headache frequency, severity, and acute medication use were collected through preadmission and postadmission clinic notes. Safety and tolerability were evaluated. Results were evaluated using descriptive statistics and compared with paired t -tests. Forty-five patients were identified for review. Patients with CM had a median of 7 previous preventive trials, and 85% had previously received alternative intravenous treatment for headache. Baseline headache pain significant decreased from 6.9/10 to 5.4/10 by 7-week postadmission follow up, (95% confidence interval = −0.7 to −2.4), P < 0.001. Use of medications for acute headache treatment decreased significantly from 2.1 days/week to 1.5 days/week, (95% confidence interval = −0.3 to −1), P < 0.001. Baseline headache frequency did not significantly change. At postadmission follow-up, 26 of 39 (67%) patients saw improvements in headache frequency, headache intensity, and/or acute pain medication usage. There were no serious adverse events. Repetitive sodium valproate infusions were well tolerated and significantly reduced baseline headache intensity and acute medication usage in pediatric patients with refractory, chronic headache disorders. [ABSTRACT FROM AUTHOR]

Background and Aims: Headache is the most common reason for referring to a physician. Therapeutic approaches of this condition include the treatment of the acute attacks and prevention of future attacks. In this regard, this study aimed to investigate the effect of three medications, namely levetiracetam, sodium valproate, and nortriptyline on the control of migraine headaches in patients with migraine referred to Birjand Neurology Clinic, Birjand, Iran. Materials and Methods: This study was conducted based on a quasi-experimental research method. According to the physician, 120 migraine patients were divided into three groups of levetiracetam (a daily dose of 250 mg), sodium valproate (500 mg), and nortriptyline (25 mg) for four weeks. A questionnaire was used to collect the demographic characteristics of the patient. The data were analyzed using SPSS software (version 16) through the chi-square tets, paired t-test, and ANOVA. Results: The patients (n=120) were divided into three groups of 40 cases per group. The mean age of the patients was 33±11 years, and the majority of the cases (53.3%) were female. In total, 46.7% of the cases had severe headache before taking these medications; however, none of them experienced severe headache after taking the medicine. It should be noted that 77.5% of the patients experienced mild headache. The group taking levetiracetam showed the greatest decrease in headache intensity (P=0.01). Conclusion: According the results, levetiracetam appears to be more effective than the other two medications, especially sodium valproate, in terms of the mitigation of different degrees of headache.

Background: The aim of this research was to study the regularities of changes in blood biochemical parameters in outbred rats exposed to the toxic effect of sodium valproate (SV) in the experiment. Methods and Results: The study was performed on 94 white outbred male rats, weighing 190-210g. According to the research protocol, all animals were divided into two groups: Intact Group (IG, n=30) and Experimental Group (EG, n=64). Animals of EG were given the anticonvulsant SV in a toxic dose of 600 mg/kg, intragastrically, once a day, for 7 (n=23), 14 (n=13), 21 (n=13) and 28 (n=15) days. The animals were withdrawn from the experiment after 7, 14, 21 and 28 days using diethyl ether. The following biochemical parameters in blood serum were determined: AST (aspartate aminotransferase), ALT (alanine aminotransferase), ALP (alkaline phosphatase), GGT (γ-glutamyltransferase), TP (total protein), glucose, direct bilirubin, TC (total cholesterol), and TG(triglycerides). The administration of toxic doses of SV to experimental animals was accompanied by changes in the biochemical status of blood, especially pronounced on Days 21 and 28 of the experiment. In particular, the activity of enzymes AST, ALT, ALP, GGT increases, the levels of TP and glucose decrease, and the levels of direct bilirubin, TG and TC, increase. Conclusion: The obtained data showed that the overdose of SV significantly worsens the blood biochemical parameters, which may indicate a toxic damage of hepatocytes. The studied biochemical parameters should be used to assess late effects of anticonvulsants on the body.

Objective: to investigate the effect of dexketoprofen on the severity of seizures on a rat model of primary generalized seizures caused by thiosemicarbazide; to evaluate the neuroprotective effect of the drug.Material and methods. The investigation was conducted on 72 male albino rats weighing 200–300 g. The animals were given dexketoprofen and/or comparison drugs (gabapentin, sodium valproate) for 5 days, after which the seizure model was reproduced. The effects of the drugs were evaluated from a set of neurological tests and the results of a histopathological examination of the brain.Results and discussion. Dexketoprofen reduced the severity, duration, and number of primary generalized seizures and potentiated the anticonvulsant effects of gabapentin and sodium valproate. Histopathological and morphometric examinations of the rat brain showed that dexketoprofen inhibited the formation of irreversible neuronal changes (27.2%; control, 55.7%), by transferring them into reversible changes (47.7%; control, 21.8%).Conclusion. The investigation made it possible to conclude that dexketoprofen had a moderate neuroprotective effect neurologically and morphometrically verified.

Objective To investigate expression changes of phospholipase C-γ1 (PLCγ1)/inositol triphosphate receptor (IP3R)/calmodulin-dependent kinase Ⅱ (CaMKⅡ) and density of dendritic spine in the hippocampus of autism model mice induced by sodium valproate (VPA). Methods Pregnant C57 mouse was given intraperitoneal injection of 300 mg/kg VPA or same volume of normal saline at the 10th and 12th days of gestation. The offspring exposed to VPA or saline during gestation were identified as autism spectrum disorder mice (VPA group) or normal control mice (CON group). Western blotting was used to detect the expression levels of PLCγ1, IP3R, CaMKⅡ and post-synaptic dense-95 (PSD95) in the hippocampus of the 2 groups. Golgi staining was employed to observe the changes in dendritic spines in the hippocampus of the offspring mice. Results Western blotting showed that the expression levels of PLCγ1, IP3R, CaMKⅡ and PSD95 were decreased in the VPA group than the normal control group (P < 0.01). Golgi staining indicated that compared with the normal control group, the density of dendritic spines in the hippocampus of VPA mice was reduced (P < 0.01). Conclusion In the hippocampus of VPA induced autism mice, the expression of PLCγ1/IP3R/CaMKⅡ and PSD95 and the dendritic spine density of pyramidal neurons in hippocampal CA1 are all decreased compared with the normal control mice.

Objective To investigate the apoptosis-inducing effect of sodium valproate (VPA) on nerve cells and the underlying mechanism. Methods Human neuroblastoma SH-SY5Y cells treated with VPA of difterent doses were examined for apoptosis and Mcl-1 protein expression using flow cytometry and Western blotting, respectively. The mRNA expression of Mcl-1 and miR-148a-3p in the treated cells was detected with qRT-PCR, and the promoter activity of Mcl-1 gene was analyzed using a reporter gene assay. The changes of cell apoptosis and Mcl-1 expression in SH-SY5Y cells were analyzed following combined treatment with VPA and a miR-148a-3p antagonist. Results VPA treatment significantly promoted apoptosis and down-regulated Mcl-1 expression at both the mRNA and protein levels in SH-SY5Y cells. VPA treatment did not significantly affect the transcriptional activity of Mcl-1 promoter but up-regulated the expression of miR-148a-3p in SH-SY5Y cells. The application of the miR-148a-3p antagonist obviously attenuated the inhibitory effect of VPA on Mcl-1 expression and VPA-induced apoptosis in the cells. Conclusion VPA promotes the apoptosis of SH-SY5Y cells by activating miR-148a-3p/Mcl-1 signaling pathway.

Aim: This study examines the effect of alpha-lipoic acid (ALA) on sodium valproate-induced liver injury through histological features of mice liver tissue. Materials and Methods: Mice were divided into three groups; (1) vehicle group, (2) sodium valproate group, and (3) sodium valproate-ALA group. The vehicle group was injected with saline intraperitoneal (i.p.) for 28 days. The sodium valproate group was injected with sodium valproate 300 mg/kg, i.p. daily for 2 weeks, after which the vehicle was administered daily until day 28. The sodium valproate-ALA group was injected with sodium valproate 300 mg/kg daily for 2 weeks before the administration of ALA 100 mg/kg i.p. until day 28. The mice were euthanized, and the liver was extracted for histopathological examination. Results: Histopathological examination of the liver section of the vehicle group showed a normal structure of the liver. Two weeks after the administration of sodium valproate, histopathological examination showed an abnormal structure of the liver, with necrotic appearance and inflammatory cells. Moreover, treatment with ALA after the administration of sodium valproate notably ameliorated hepatic histopathological lesions and the liver structure corresponded to a normal liver structure. Conclusion: ALA ameliorates sodium valproate-induced liver injury in mice.

Abstract Valproic acid in association with sodium valproate (VPA) is an important anticonvulsant drug used for decades to treat neurological disorders. VPA also acts as an epigenetic modulator by inhibiting histone deacetylases, permitting histone acetylation, affecting the DNA and histone methylation status and gene expression, and inducing chromatin remodeling. Insects represent an important animal model for studies in several areas of science. Their high phenotypic plasticity makes them alternative models for epigenetic studies. This brief review emphasizes recent reports on insect epigenetics and the contribution of studies on the VPA action in insects, including effects on epigenetic markers, extending the pharmacological understanding of the potential of this drug, and demonstrating the usefulness of insects as an alternative animal model to drug studies.

Purpose: Sodium Valproate (VPA) is one of the first-generation Antiepileptic Drugs (AEDs) which mediates epileptic activities by releasing stimulators of Gamma-Aminobutyric Acid (GABA) and is greatly used to treat partial and generalized seizures. Lamotrigine )LTG( is commonly used as AEDs that are widely utilized in first-line monotherapy or in combination with other AEDs. Our specific goal was to compare these two AEDs with different molecular mechanisms on both cortical and subcortical brain structures, along with cognitive performance and dysfunctions. Materials and Methods: We conducted a retrospective study comparing LTG with sodium VPA, both administrated as monotherapy. Twenty patients with a confirmed generalized-epilepsy tonic-clonic seizure who had been treated at least 6 months with LTG (n=8) and Sodium VPA (n=12) were retrospectively recruited. We also included 12 age, gender, and education-matched Healthy Controls (HC). We evaluated cognitive performances. All participants underwent a Magnetic Resonance Imaging (MRI) scanner and T1-weighted MR images were acquired. Voxel-based morphometric alterations in the brain cortex, as well as subcortical structures, were inspected using Statistical Parametric Mapping (SPM) software. Results: The cognitive performance was revealed inferior in patients on Sodium VPA. Poor performance was associated with significant volume reduction in insula bilaterally, and subcortical structures of thalamus, cerebellum, and hippocampus compared to the HC. Comparing patients on LTG to HC revealed significant volume reduction in the anterior cingulate cortex in concordance with slight cognitive dysfunctions. Conclusion: These findings suggested that different molecular mechanisms of Antiepileptic Drugs (AEDs) may affect brain structures and cognition with different severity levels, presumably with more adverse effects induced by GABA mediations from sodium VPA.

Abstract We report a 5‐year‐old girl with a generalized seizure treated with sodium valproate syrup. She returned to the clinic with Henoch–Schonlein purpura after 20 days due to the consumption of sodium valproate. To our knowledge, this is the second case of sodium valproate‐induced HSP.

Background: Among antiepileptic drugs (AEDs), sodium valproate alone or in the combination of topiramate (TPM) for treating refractory epilepsy was controversial. This meta-analysis aimed to systematically evaluate the clinical effects of these two regimens in this population.Methods: Relevant studies up to August 2021 were identified through systematic searches of CNKI, Wanfang, PubMed, and Embase databases. We assessed the effectiveness and the frequency of absence seizures, atonic seizures, and tonic–clonic seizures. The included literature's risk of bias was evaluated using the Cochrane Collaboration's Risk of Bias tool. Sensitivity analysis was conducted to confirm the results' stability. STATA 15.0 was utilized for all pooled analyses in the included studies.Results: Totally 10 articles were determined for our meta-analysis, involving 976 patients with epilepsy in total (combined group, n = 488; monotherapy group, n = 488). The results of this meta-analysis indicated that the total effective rate of sodium valproate combined with TPM was higher than that of sodium valproate alone (random-effect model: OR = 3.52; 95% CI 1.47 to 8.47; p < 0.001; I2 = 73.8%). The frequency of absence seizures in the combined group was lower (fixed-effect model: WMD = −6.02; 95% CI −6.50 to −5.54; I2 = 0.0%) than that in the monotherapy group, with a statistical difference (p < 0.05). The combined group had lower frequency of atonic seizures (WMD = −4.56, 95% CI −6.02 to −3.10; I2 = 82.6%) and lower frequency of tonic–clonic seizures (WMD = −3.32; 95% CI −4.75 to −1.89; I2 = 96.4%). In addition, the distinct difference of adverse events was non-existent between two groups.Conclusions: Sodium valproate combined with TPM was more effective than sodium valproate alone for epilepsy therapy. This meta-analysis provides feasibility data for a larger-scale study on AED therapy of refractory epilepsy and may contribute to better therapy strategies for epilepsy clinically.

Objective: To estimate the safety and efficacy of sodium valproate combined with levetiracetam in paediatric patients with epilepsy based on randomized controlled trials (RCTs).Methods: The Cochrane Library, PubMed, Web of Science, Chinese Journal Full-Text Database (CNKI), WANGFANG DATA and Sino Med were searched between January 1946 and May 2021. The included literature was randomized controlled clinical trials focusing on sodium valproate combined with levetiracetam in paediatric patients with epilepsy. Two evaluators separately collected the data based on the retrieval strategy, filtered the literature in accordance with the inclusion and exclusion criteria, and summarized the literature that satisfied the criteria. The statistical programme used for the meta-analysis was Stata V14.0.Results: Of 577 original titles screened, data were extracted from 7 studies (617 participants). Compared with sodium valproate alone or sodium valproate combined with topiramate, the application of sodium valproate combined with levetiracetam in the treatment of paediatric epilepsy significantly improved the overall therapeutic effect (RR=1.24, 95% CI: 1.16 to 1.33, p=0.927). The observation group significantly reduced the occurrence of adverse drug reactions (ADRs) (RR=0.54, 95% CI: 0.37 to 0.79, p=0.602). Egger's regression test of the overall therapeutic effect showed no potential publication bias (p=0.122).Conclusion: Based on this meta-analysis, compared with sodium valproate alone or sodium valproate with topiramate, the application of sodium valproate combined with levetiracetam in the treatment of paediatric epilepsy can significantly improve the overall therapeutic effect and simultaneously reduce the occurrence of ADR. Therefore, we recommend sodium valproate combined with levetiracetam for the therapy of paediatric patients with epilepsy. [ABSTRACT FROM AUTHOR]

Background: Among antiepileptic drugs (AEDs), sodium valproate alone or in the combination of topiramate (TPM) for treating refractory epilepsy was controversial. This meta-analysis aimed to systematically evaluate the clinical effects of these two regimens in this population. Methods: Relevant studies up to August 2021 were identified through systematic searches of CNKI, Wanfang, PubMed, and Embase databases. We assessed the effectiveness and the frequency of absence seizures, atonic seizures, and tonic–clonic seizures. The included literature's risk of bias was evaluated using the Cochrane Collaboration's Risk of Bias tool. Sensitivity analysis was conducted to confirm the results' stability. STATA 15.0 was utilized for all pooled analyses in the included studies. Results: Totally 10 articles were determined for our meta-analysis, involving 976 patients with epilepsy in total (combined group, n = 488; monotherapy group, n = 488). The results of this meta-analysis indicated that the total effective rate of sodium valproate combined with TPM was higher than that of sodium valproate alone (random-effect model: OR = 3.52; 95% CI 1.47 to 8.47; p < 0.001; I 2 = 73.8%). The frequency of absence seizures in the combined group was lower (fixed-effect model: WMD = −6.02; 95% CI −6.50 to −5.54; I 2 = 0.0%) than that in the monotherapy group, with a statistical difference (p < 0.05). The combined group had lower frequency of atonic seizures (WMD = −4.56, 95% CI −6.02 to −3.10; I 2 = 82.6%) and lower frequency of tonic–clonic seizures (WMD = −3.32; 95% CI −4.75 to −1.89; I 2 = 96.4%). In addition, the distinct difference of adverse events was non-existent between two groups. Conclusions: Sodium valproate combined with TPM was more effective than sodium valproate alone for epilepsy therapy. This meta-analysis provides feasibility data for a larger-scale study on AED therapy of refractory epilepsy and may contribute to better therapy strategies for epilepsy clinically. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the characteristics of steady-state blood concentration of sodium valproate in children with epilepsy of different ages and its correlation with epileptic control and adverse drug reactions( ADR ) based on the significantly age-dependent developmental characteristic of the metabolic process of valproate, so as to obtain the safety and efficacy data of sodium valproate in pediatrics. METHODS: A total of 748 children diagnosed with epilepsy and treated with sodium valproate in the department of neurology in this hospital from Jan. 2017 to Jun. 2020 were included. The early morning fasting venous blood was collected 3 d after the oral administration, the concentration of sodium valproate in the plasma was measured, and the frequency of epilepsy, nervous system reaction, gastrointestinal reaction and ADR of skin were recorded. RESULTS: The steady-state blood concentration of valproate showed a significant stepwise increase with age, and the mean blood concentration of valproate was (50. 06±28. 18) mg/Lin epilepsy children <1 year old, (51. 08±18. 71) mg/Lin children aged from 1 to 2 years, and ( 59. 87±22. 07) mg/Lin children aged from >2 to 6 years, which was significantly higher than that in the group of children aged from 1 to 2 years, the difference was statistically significant( P6 to 14 years old, higher than that of children aged from > 2 to 6 years old, but the difference was not statistically significant ( P>O. 05), and significantly higher than that of children aged from 1 to 2 years old ( P < 0. 001 ) and < 1 years old ( P < 0. 01 ), the differences were statistically significant. Steady-state blood concentration of sodium valproate were lower in the low-dose group [ <20 mg/ ( kg · d ) ] than in the medium-dose[ from 20 mg/(kg·d) to 30 mg/(kg·d) J and high-dose group[ >30 mg/( kg ·d) J, but the blood concentration of sodium valproate in patients in the medium-dose and high-dose group did not show the dose correlation. The control rates of epilepsy in sodium valproate medium and high blood concentration group were respectively 90. 0%(387/430) and 91. 1%(41145), significantly higher than those in low blood concentration group 70. 0% ( 191/273), with statistically significant difference ( P < 0. 05) . A total of 39 ADR cases were collected, and the most common ADR cases were neurological reactions ( 14 cases), impaired liver function ( 11 cases) and digestive reactions ( 9 cases). The incidence of ADR tended to increase with increasing blood concentration of sodium valproate and showed an age correlation, and the incidence of ADR was significantly higher in children with epilepsy in the younger age group ≤ 2 years old than in children with epilepsy in other age groups ( from > 2 to 14 years old ) . CONCLUSIONS: ( 1) The blood concentration and ADR of sodium valproate in children have age-specific distribution characteristics, and the blood concentration of infants and children ( ≤ 2 years old) is easily lower than the minimum therapeutic concentration, but more likely to have adverse drug reactions, which should be closely monitored in clinic . ( 2) The safety and efficacy of sodium valproate are satisfactory when the blood concentration of sodium valproate in children is controlled within the range from 50 mg/L to 100 mg/L. ( 3) Compared with adults, the incidence of liver damage in children is higher, and the monitoring of corresponding indicators of liver function should be strengthened during the administration of valproate sodium. [ABSTRACT FROM AUTHOR]

Background: Bipolar affective disorder (BD) is a chronic recurrent disorder having a definite link with metabolic abnormalities, including obesity, dyslipidemia, and insulin resistance. Drugs approved for the treatment of BD include sodium valproate but have weight gain as a metabolic side effect. An increase in weight is one of the common reasons for discontinuation of mood stabilizers. There is a need for a weight loss agent which will not increase mood symptoms in bipolar disorder. This study looks at the effect of acetazolamide on weight when combined with sodium valproate in patients diagnosed with BD in remission. Materials and Methods: This pilot quasi-experimental open-label 8-week follow-up study was conducted in a tertiary care teaching hospital following clearance from the institutional ethics committee. Thirteen outpatients with BD who reported weight gain on sodium valproate monotherapy received oral acetazolamide 500 mg/day. A specialized pro forma was used to record demographic and physical data with side effects. Results: The mean baseline weight was 70.15 ± 8.75 kg and the mean baseline body mass index was 25.09 ± 2.61. The mean sodium valproate dose of the study population was 692 mg/day. Ten of 11 individuals who completed the study showed some reduction in weight and nine showed a slight decrease in abdominal girths. Conclusion: There was a nonsignificant decrease in weight and abdominal circumferences at the end of 8 weeks, however, since it is a small pilot study, we need more evidence. [ABSTRACT FROM AUTHOR]

Background: Case reviews of severe cutaneous adverse drug reactions (ADRs) such as SJS/TEN provide useful insights for clinical characteristics, putative drugs, and management protocols. Patients and Methods: Medical charts of 62 (m:f- 20:42) patients with SJS/TEN hospitalized between 2010 and 2019 were analyzed retrospectively for clinical attributes, putative drugs and their indications, extracutaneous complications, and therapeutic outcome. The diagnosis was clinical based on established criteria. WHO-UMC scale for reporting ADR and ALDEN algorithm score were used for causality assessment. Therapies were customized based on in-house resources and affordability. Results: Cases included were SJS (41.9%), SJS/TEN overlap (33.9%), and TEN (24.2%) aged 4–85 years. Complications included transaminitis (69.4%), lymphadenopathy (15.5%), septicemia (11.3%), and wound infections (4.8%). Aromatic anticonvulsants (37.1%), disease-modifying antirheumatic drugs (25.8%), antiretroviral drugs (12.9%), non-steroidal anti-inflammatory drugs (8.1%), antimicrobials (4.8%), and trihexyphenidyl (3.2%) were major putative drugs. The mean latent period was 16.6 days. The observed 8% mortality was because of primary comorbidities or multiorgan failure. Addition of fresh blood transfusion (BT, n = 11) or IVIg (n = 7) to systemic corticosteroids showed early relief in skin tenderness, improvement in general condition, and re-epithelialization. Only 16% of patients developed sequelae. Conclusion: Aromatic anticonvulsants, allopurinol, nevirapine, cotrimoxazole, paracetamol, and diclofenac remain the most implicated drugs. Sulfasalazine, leflunomide, ethambutol, and trihexyphenidyl were uncommon additions. A short course of high-dose dexamethasone in the early stage was useful. Addition of BT or IVIg provided rapid relief. Preexisting HIV disease, kidney disease, and sepsis remain important for in-hospital deaths. Retrospective study design and small number of cases remain major limitations. [ABSTRACT FROM AUTHOR]

Epilepsy is a common chronic neurological disease that manifests as recurrent seizures. The incidence and prevalence of epilepsy in women are slightly lower than those in men. Polycystic ovary syndrome (PCOS), a reproductive endocrine system disease, is a complication that women with epilepsy are susceptible to, and its total prevalence is 8%–13% in the female population and sometimes as high as 26% in female epilepsy patients. The rate of PCOS increased markedly in female patients who chose valproate (VPA), to 1.95 times higher than that of other drugs. In addition, patients receiving other anti-seizure medications (ASMs), such as lamotrigine (LTG), oxcarbazepine (OXC), and carbamazepine (CBZ), also have reproductive endocrine abnormalities. Some scholars believe that the increase in incidence is related not only to epilepsy itself but also to ASMs. Epileptiform discharges can affect the activity of the pulse generator and then interfere with the reproductive endocrine system by breaking the balance of the hypothalamic–pituitary–ovarian (HPO) axis. ASMs may also cause PCOS-like disorders of the reproductive endocrine system through the HPO axis. Moreover, other factors such as hormone metabolism and related signalling pathways also play a role in it. [ABSTRACT FROM AUTHOR]

Ischemic stroke caused by atherosclerosis (AS) poses a serious threat to human life expectancy and quality. With the development of genome-wide association studies, the association of histone deacetylase 9 (HDAC9) expression of atheromatous plaques with ischemic stroke in large arteries has been revealed, but the molecular mechanisms behind this phenomenon have not been elucidated. In this study, we explored the effect of HDAC9 on the P38 mitogen activated protein kinase (P38 MAPK), a classic cellular inflammation-related pathway, by knocking down HDAC9 in vascular endothelial cells with short hairpin RNA (shRNA) and found that HDAC9 may mediate oxidized low density lipoprotein (ox-LDL)-induced inflammatory injury in vascular endothelial cells by regulating the phosphorylation level of P38 MAPK to lead to AS. It can be seen that HDAC9 may be a target to control the formation of atherosclerotic plaques. In follow-up experiments, it was verified that sodium valproate (SVA), as a HDAC9 inhibitor, can indeed antagonize the inflammatory damage of vascular endothelial cells, as well as SB203580, which is a P38 MAPK inhibitor. It proves that SVA may be a potential drug for the prevention and treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Epilepsy is a common chronic neurological disease that manifests as recurrent seizures. The incidence and prevalence of epilepsy in women are slightly lower than those in men. Polycystic ovary syndrome (PCOS), a reproductive endocrine system disease, is a complication that women with epilepsy are susceptible to, and its total prevalence is 8%–13% in the female population and sometimes as high as 26% in female epilepsy patients. The rate of PCOS increased markedly in female patients who chose valproate (VPA), to 1.95 times higher than that of other drugs. In addition, patients receiving other anti-seizure medications (ASMs), such as lamotrigine (LTG), oxcarbazepine (OXC), and carbamazepine (CBZ), also have reproductive endocrine abnormalities. Some scholars believe that the increase in incidence is related not only to epilepsy itself but also to ASMs. Epileptiform discharges can affect the activity of the pulse generator and then interfere with the reproductive endocrine system by breaking the balance of the hypothalamic–pituitary–ovarian (HPO) axis. ASMs may also cause PCOS-like disorders of the reproductive endocrine system through the HPO axis. Moreover, other factors such as hormone metabolism and related signalling pathways also play a role in it.

Faces convey a great amount of socially relevant information related to emotional and mental states, identity and intention. Processing of face information is a key mechanism for social and cognitive development, such that newborn babies are already tuned to recognize and orient to faces and simple schematic face-like patterns since the first hours of life. Similar to neonates, also non-human primates and domestic chicks have been shown to express orienting responses to faces and schematic face-like patterns. More importantly, existing studies have hypothesized that early disturbances of these mechanisms represent one of the earliest biomarker of social deficits in autism spectrum disorders (ASD). We used VPA exposure to induce neurodevelopmental changes associated with ASD in domestic chicks and tested whether VPA could impact the expression of the animals’ approach responses to schematic face-like stimuli. We found that VPA impairs the chicks’ preference responses to these social stimuli. Based on the results shown here and on previous studies, we propose the domestic chick as animal model to investigate the biological mechanisms underlying face processing deficits in ASD.

People with intellectual disability (ID) have a greater frequency of psychiatric illnesses, ranging from 10% to 80%, as compared to the general population. It has been proven that mood stabilizers are beneficial in the management of behavior issues in people with ID. Here, we report a series of five cases with mild and moderate ID with behavioral disturbances including mood and psychotic symptoms managed successfully with sodium valproate as the part of the treatment.

Faces convey a great amount of socially relevant information related to emotional and mental states, identity and intention. Processing of face information is a key mechanism for social and cognitive development, such that newborn babies are already tuned to recognize and orient to faces and simple schematic face-like patterns since the first hours of life. Similar to neonates, also non-human primates and domestic chicks have been shown to express orienting responses to faces and schematic face-like patterns. More importantly, existing studies have hypothesized that early disturbances of these mechanisms represent one of the earliest biomarker of social deficits in autism spectrum disorders (ASD). We used VPA exposure to induce neurodevelopmental changes associated with ASD in domestic chicks and tested whether VPA could impact the expression of the animals' approach responses to schematic face-like stimuli. We found that VPA impairs the chicks' preference responses to these social stimuli. Based on the results shown here and on previous studies, we propose the domestic chick as animal model to investigate the biological mechanisms underlying face processing deficits in ASD. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To systematically evaluate the clinical efficacy and safety of lamotrigine combined with sodium valproate in the treatment of seizure. METHODS: PubMed, the Cochrane Library, Embase, CNKI, Wanfang database and VIP database were retrieved to collect the randomized controlled trials of lamotrigine combined with sodium valproate in the treatment of seizure（ the study group was treated with lamotrigine combined with sodium valproate, while the control group received sodium valproate）. The retrieval time was from the establishment of the database to Jan. 2021. The modified Jadad scale was used to evaluate the quality of the literature, efficiency, seizure frequency, seizure duration and high-sensitivity C-reactive protein levels were extracted as the parameters. Meta-analysis, sensitivity analysis and publication bias test were performed by using Rev Man 5. 3 software. RESULTS: A total of 18 randomized controlled trials that met the criteria were included in the literature, with a total of 1 430 cases（ 713 in the study group and 717 in the control group）. Meta-analysis results showed that the differences of total effective rate（ OR = 3. 90,95% CI = 2. 85-5. 33,Z = 8. 51,P < 0. 000 01） and seizure duration（ MD =-3. 27,95% CI =-3. 59--2. 95,Z = 20. 16,P <0. 000 01）,seizure frequency（ MD =-1. 82,95% CI =-2. 21--1. 43,Z = 9. 17,P < 0. 000 01） and high-sensitivity Creactive protein level（ MD =-3. 79,95% CI =-4. 05--3. 53,Z = 28. 65,P < 0. 000 01） in two groups were statistically significant, and the levels of above indicators in the study group were significantly better than those in the control group. The incidence of adverse drug reactions in the study group was lower than that in the control group,and the difference was statistically significant（ OR = 0. 45,95% CI = 0. 33-0. 62,Z = 4. 99,P < 0. 000 01）.CONCLUSIONS: Lamotrigine combined with sodium valproate in the treatment of seizure is better than valproate alone in the comprehensive efficacy and adverse drug reactions, and significantly better than that of valproate alone in reducing seizure frequency, shortening seizure duration, and lowering hypersensitive C-reactive protein levels. [ABSTRACT FROM AUTHOR]

Objectives Epilepsy is a relatively common disease in childhood. In some patients, the electroencephalogram (EEG) is abnormal despite the clinical control of seizures. Studies have identified the adverse effects of epileptic discharges on cognition, learning, behavior, and seizure recurrence in children. This study investigated the Levetiracetam effect on epileptic discharges in the interictal phase of EEG in epileptic children. Materials & Methods This clinical trial was conducted on 54 epileptic children aged 2 to 15 years, whose clinical seizures were controlled by sodium valproate in the last six months but still had epileptic discharges in EEG. The participants were divided into two groups: an intervention group (21 people), for which Levetiracetam was added to sodium valproate, and a control group (33 people), for which treatment with sodium valproate alone was continued. The patients were then followed for one year. Results The percent normalization of epileptic discharges in the intervention and control groups was 66.7% and 57.1% (P = 0.500), respectively. Also, the mean time for the normalization of epileptic discharges in the intervention and control groups was 12.60±8.25 and 20.57±12.67 months (P = 0.042), respectively. Conclusion In children with controlled seizures whose EEG was still abnormal, sodium valproate therapy alone and combined with Levetiracetam effectively reduced the severity of epileptic discharges. However, the addition of Levetiracetam to sodium valproate normalized EEG more rapidly. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the frequently diagnosed cancers worldwide. Currently used chemotherapeutic drugs have several side effects. Histone deacetylase (HDAC) enzyme inhibitors possess potential anti-cancer effects. Therefore, we investigated the cytotoxic potential of sodium valproate, a HDAC inhibitor in human colorectal adenocarcinoma (HT-29) cells. Methods: MTT assay was used to analyze the cytotoxicity of HT-29 cells. Intracellular reactive oxygen species (ROS) induction was evaluated by dichloro-dihydro-fluorescein diacetate staining. Dual staining with acridine orange/ethidium bromide was used to investigate the morphology-related apoptotic cell death. Mitochondrial membrane potential was analyzed by rhodamine 123 staining. E-cadherin protein expression was examined by immunofluorescence staining. Results: Sodium valproate at 2 and 4 mM/mL treatments significantly induced cytotoxicity. Increased intracellular ROS expression was observed in the cells treated with sodium valproate. This treatment also induced mitochondrial dissipation, apoptosis-related morphological damage, and E-cadherin expression in HT-29 cells. Conclusions: Our present results suggest that sodium valproate is cytotoxic to HT-29 cells due to its pro-oxidative and apoptosis inducing potential. Sodium valproate can be used as an adjuvant along with standard chemotherapeutic agents in CRC patients after necessary in vivo and clinical studies. [ABSTRACT FROM AUTHOR]

Chinese hamster ovary cells are widely used in various biopharmaceutical industries as preferred host cells for the production of recombinant proteins. In an effort to increase yield and reduce production costs, the incorporation of small molecule additives into the culture medium has emerged as an effective approach to augment the expression of recombinant proteins, thus increasing overall efficiency. Here, we examined the impact of five small molecules on protein expression in CHO-engineered cell lines. These molecules included sodium valproate, alanyl-L-tyrosine, ascorbic acid, sodium citrate and ferrous sulphate. Their optimal concentrations were determined through univariate analysis aimed at enhancing cell growth and protein production. Our findings revealed that inoculating cells at a density of 1.0 × 106 cells/mL with the simultaneous addition of sodium valproate at a concentration of 2 mM for 0 h yielded the most favorable results. Notably, while valproate inhibited cell growth in a dose-dependent manner, it simultaneously extended cell culture longevity. Additionally, sodium valproate was observed to decrease glucose consumption, collectively increasing protein expression. In conclusion, our data suggest that sodium valproate is a potent chemical agent capable of increasing the production of recombinant protein in CHO cells. This enhancement is achieved by the modulation of metabolic pathways in CHO-engineered cell lines, thereby facilitating a state of low metabolism and high protein expression. • Sodium valproate (VPA) can prolong the culture time of CHO cells by weakening the consumption of glucose. • VPA is a potent chemical agent that promotes low metabolism and high expression of CHO-engineered cell lines. • Seeded cells at a density of 1.0 × 106 cells/mL with adding 2.0 mM VPA at 0 h can improve the performance of CHO cells. • VPA increases the yield of recombinant proteins by inducing cell cycle arrest in the G2/M phase. [ABSTRACT FROM AUTHOR]

Nuclear factor erythroid factor 2 (Nrf2) is the key regulatory of the antioxidant response elements. Also, Nrf2 interacts with nuclear factor kappa B (NF-ĸB) to inhibit subsequent inflammatory cascade. Activation of Nrf2 signaling ameliorates drug-induced liver injury. Sodium valproate (SVP) is an anti-epilepsy drug with a hepatotoxic adverse effect that restricts its clinical use. In this study, coadministration of Dihydromyricetin (DHM), a natural flavonoid, with SVP to rats upregulated gene expression of Nrf2 and its downstream gene, heme oxygenase 1 (HO-1), while suppressed the Nrf2 repressor, Keap-1. Additionally, DHM led to downregulation of proinflammatory factors in liver tissues, including NF-ĸB, interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α). This was accompanied by a decrease in the proapoptotic protein (cleaved caspase-3) expression level. Furthermore, biochemical and histopathological studies showed that DHM treatment improved liver function and lipid profile while decreased inflammatory cell infiltration, congestion, and hepatocellular damage. According to our knowledge, prior research has not examined the protective effect of DHM on the liver injury induced by SVP. Consequently, this study provides DHM as a promising herbal medication that, when used with SVP, can prevent its induced hepatotoxicity owing to its potential anti-oxidative, anti-inflammatory, and anti-apoptotic properties. [Display omitted] • The anti-epileptic sodium valproate drug induces liver injury that limits its use. • Dihydromyricetin promotes Keap-1 inactivation with Nrf2/HO-1 signaling activation. • Dihydromyricetin inhibits NF-ĸB/caspase-3 signaling pathway. • Dihydromyricetin alleviates liver injury adverse effect of sodium valproate. [ABSTRACT FROM AUTHOR]

Background and Aims: Anticonvulsants are used routinely for seizure prophylaxis in patients with supratentorial tumour who present with/without seizures. Excessive use of prophylactic anticonvulsant may delay the recovery from anaesthesia. We have studied the recovery profiles of patients who received an additional dose of anticonvulsant in comparison with those who received only the regular dose. Methods: In this prospective observational study, patients were anaesthetised using standard anaesthesia protocol. An additional dose of anticonvulsant was administered in one group, while the other group received only the regular dose. Time taken for extubation, eye opening, obeying commands and orientation were compared between the two groups. Haemodynamics, depth of anaesthesia, the plasma anticonvulsant levels and the incidence of seizures were compared between the two groups. Results: A total of 36 patients were studied, of which 19 received regular dose and 17 received an additional dose. There was no significant difference in recovery time between the two groups. Subgroup analysis was performed for phenytoin and sodium valproate. There was a clinically significant delay in recovery in patients who received an additional phenytoin compared to those who received regular dose (time to obey commands >15 min and orientation time >1hour) but, it was not statistically significant. Administration of an additional dose of valproate did not prolong the recovery time. Conclusion: An additional dose of sodium valproate did not cause a delay in recovery both, clinically and statistically. However, the administration of an additional dose of phenytoin caused a clinically significant delay in recovery but was not statistically significant.

Introduction: Consuming antidepressant medications induce several problems leading to the need for alternative agents for emotional disturbances. Antidepressant medications increase the seizure risk; thus, alternative treatments, like Antiepileptic Drugs (AED), might be useful for patients with epilepsy comorbid with a psychiatric disorder. The present study evaluated the behavioral effects of sodium valproate, a none effective dose in seizure treatment [100 mg/kg; Intraperitoneal (IP)] along with the application of Low-Frequency Stimulations (LFS) during CA1 hippocampal kindling. Methods: In total, 42 male rats were randomly divided into 6 groups, including control group with intact animals handled daily (I); sham group which was subjected to the surgical process, but received no real stimulation (II); saline-kindled Kindled group (S.kindled) which were stimulated daily with the following protocol: 3 strain of 50Hz monophasic pulses of 1ms duration applied 12 times a day with the threshold intensity at intervals of 10 minutes where saline was administrated 15 min before kindling stimulations (III); saline-kindled-LFS group (K4LFS) in which saline was injected 15 min before kindling stimulations and LFS was applied daily after the termination of kindling stimulation (IV ); drug-kindle group (Drug100.kindled) that underwent rapid kindling procedure daily where sodium valproate (100 mg/kg) was administrated 15 min before kindling stimulations(V), and drug-kindled-LFS (Drug100.kindled.4LFS) group in which drug and LFS were administrated respectively before and after kindling stimulations (VI). The behavioral tests were assessed using elevated plus maze, open field, and forced swim tests. Results: The combination of sodium valproate (100 mg/kg) and LFS significantly decreased cumulative seizure severity compared with the kindle group. Thus, it provided a strong seizure suppressing effect. Additionally, sodium valproate and LFS increased the percentage of Open Arms (OAs) entries and the OAs exploration; they also decreased jumping from elevated plus maze test and rearing in open field test. Furthermore, there was no significant change in the OAs entries and OAs exploration percentages, jumping from apparatus, and rearing in open field in Drug100. Kindled, K4LFS, and Drug100.kindled.LFS groups, compared with the sham group. There was no significant difference in the latency to first immobility and the duration of immobility in K4LFS groups compared with the S. kindled group. In the drug-kindled group, the latency to first immobility significantly increased, and the duration of immobility decreased, compared with the S. kindled group. Besides, the latency to first immobility significantly increased, and the duration of immobility decreased in drug-kindled-LFS, compared to S. kindled group; however, the latency to first immobility was not significantly changed, compared to drug-kindled groups. Conclusion: Sodium valproate and LFS can modulate the function of the brain regions involved in emotional processing in epilepsy, as well as anxiety- and depressive-like behaviors. Such a combination could also decrease emotional disturbances induced by the kindling process.

Abstract Objective This study compared the efficacy and tolerability of sodium valproate and aripiprazole in the treatment of Tourette syndrome (TS). Method 24 children and adolescents with a diagnosis of TS from the Jiamusi Central Hospital between January 2014 and August 2017 were randomly divided into sodium valproate group and aripiprazole group according to the order of clinic visits and treated for 10 days. Tic severity was rated using the Yale Global Tic Severity Scale (YGTSS) and the Clinical Global Impressions Scale for tics (CGI-Tics) and the adverse reactions were valued using the Treatment Emergent Symptom Scale (TESS) at baseline and at each follow-up visit. Results The TTS score in the YGTSS scale decreased over time in both groups while the aripiprazole group was significantly higher on the 5th day (p

Objectives: To compare the effect between conventional and sustained released sodium valproate monotherapy on serum leptin, body mass index (BMI) and some liver function tests including serum alkaline phosphatase (ALP), alanine amino transferase (ALT), aspartate amino transferase (AST), albumin, total bilirubin (TB) and direct bilirubin (DB) in epileptic patients. Patients and methods: The study is a case control study. It included 40 epileptic patients on conventional sodium valproate at doses 400-800 mg per day, and 42 patients on sustained released sodium valproate at doses 500-1000 mg per day. Forty healthy subjects sex and age matched served as controls were also included in the study. Blood samples were taken from the patients and controls and analyzed for serum ALT, ALP, AST, albumin, total bilirubin and direct bilirubin. Serum leptin was also analyzed by using ElISA technique. Results: Serum leptin, ALT, ALP, AST and TB in epileptic patients treated by conventional sodium valproate were significantly (p < 0.05) higher than that in patients treated with sustained release sodium valproate. However, serum albumin was significantly (p < 0.05) lower than that in patients treated by sustained released sodium valproate. No significant change was noticed between the two patients groups for BMI and serum DB Conclusion: Sustained release sodium valproate may have less hepatotoxic effect and cause less weight gain than conventional sodium valproate. The reduced frequency of doses and the possibility of dosing flexibility may all improve compliance of the patients.

Pediatric epilepsy comprises chronic neurological disorders characterized by recurrent seizures. Sodium valproate is one of the common antiseizure medications used for treatment. Glucuronide conjugation is the major metabolic pathway of sodium valproate, carried out by the enzyme uridine 5′-diphosphate (UDP) glucuronosyl transferase (UGT) whose gene polymorphisms may alter the clinical outcome. The objective of this study was to assess the association between UGT1A6 genetic polymorphism and clinical outcome in terms of efficacy and tolerability in pediatric epileptic patients on sodium valproate monotherapy. Pediatric epileptic patients (n=65) aged 2-18 years receiving sodium valproate monotherapy for the past one month were included. Genetic polymorphism patterns of UGT1A6 (T19G, A541G, A552C) were evaluated by PCR-RFLP. Clinical outcome was seizure control during the 6 months observation period. Tolerability was measured by estimating the hepatic, renal, and other lab parameters. Out of 65 patients, TT (40%), TG (57%), and GG (3%) patterns were observed in UGT1A6 (T19G) gene, AA (51%), AG (40%), and GG (9%) in (A541G) gene, and AA (43%), AC (43%), and CC (14%) in (A552C) gene. No statistical difference in clinical outcome was found for different UGT1A6 genetic polymorphism patterns. We concluded that different patterns of UGT1A6 genetic polymorphism were not associated with the clinical outcome of sodium valproate in terms of efficacy and tolerability. Sodium valproate was well-tolerated among pediatric patients with epilepsy and can be used as an effective antiseizure medication.

Machado-Joseph disease (MJD, also known as spinocerebellar ataxia type 3) is a fatal neurodegenerative disease that impairs control and coordination of movement. Here we tested whether treatment with the histone deacetylase inhibitor sodium valproate (valproate) prevented a movement phenotype that develops in larvae of a transgenic zebrafish model of the disease. We found that treatment with valproate improved the swimming of the MJD zebrafish, affected levels of acetylated histones 3 and 4, but also increased expression of polyglutamine expanded human ataxin-3. Proteomic analysis of protein lysates generated from the treated and untreated MJD zebrafish also predicted that valproate treatment had activated the sirtuin longevity signaling pathway and this was confirmed by findings of increased SIRT1 protein levels and sirtuin activity in valproate treated MJD zebrafish and HEK293 cells expressing ataxin-3 84Q, respectively. Treatment with resveratrol (another compound known to activate the sirtuin pathway), also improved swimming in the MJD zebrafish. Co-treatment with valproate alongside EX527, a SIRT1 activity inhibitor, prevented induction of autophagy by valproate and the beneficial effects of valproate on the movement in the MJD zebrafish, supporting that they were both dependent on sirtuin activity. These findings provide the first evidence of sodium valproate inducing activation of the sirtuin pathway. Further, they indicate that drugs that target the sirtuin pathway, including sodium valproate and resveratrol, warrant further investigation for the treatment of MJD and related neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the pattern of UGT1A6 and UGT2B7 gene polymorphism in pediatric epileptic patients and to compare the sodium valproate concentration in different patterns of UGT gene polymorphism. Methods: In this cross-sectional study, 99 pediatric epileptic patients aged 2–18 y receiving Sodium valproate monotherapy for the past one month were included from JusticeK S Hegde Charitable hospital, Mangalore after obtaining informed consent. Genetic polymorphism patterns were evaluated by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Trough level serum valproate concentration was estimated by high-performance liquid chromatography (HPLC). Sodium valproate concentration in different UGT genotypes was compared by Analysis of Variance (ANOVA). P value <0.05 was considered significant. Results: In the present study population, the predominant mutant allele pattern was observed in UGT1A6 (T19G, A541G, A552C) gene. In UGT2B7 (A268G, C161T) showed predominant mutant allele pattern while (G211T) showed predominant wild type. Mean steady-state sodium valproate concentration was 105.40 ± 49.9 μg/ml and adjusted sodium valproate concentration was 5.5 ± 3.2 mg/kg/L. It was found that there was no statistical difference in sodium valproate concentration in different UGT1A6 and UGT2B7 gene polymorphism. Conclusion: The present study concluded that though there was a difference in pattern of gene polymorphism with concerning UGT1A6 and UGT2B7, however, it has not contributed to variation in serum concentration of sodium valproate in the present study population. [ABSTRACT FROM AUTHOR]

Background: Sodium valproate (VPA) has been associated with a reduced risk of head and neck cancer development. The potential protective mechanism of action is believed to be via inhibition of histone deacetylase and subsequent epigenetic reprogramming. SAVER is a phase IIb open-label, randomised control trial of VPA as a chemopreventive agent in patients with high-risk oral epithelial dysplasia (OED). The aim of the trial is to gather preliminary evidence of the clinical and biological effects of VPA upon OED and assess the feasibility and acceptability of such a trial, with a view to inform a future definitive phase III study.Methods: One hundred and ten patients with high-risk OED will be recruited from up to 10 secondary care sites in the UK and randomised into either VPA or observation only for 4 months. Women of childbearing potential will be excluded due to the teratogenic properties of VPA. Tissue and blood samples will be collected prior to randomisation and on the last day of the intervention/observation-only period (end of 4 months). Clinical measurement and additional safety bloods will be taken at multiple time points during the trial. The primary outcome will be a composite, surrogate endpoint of change in lesion size, change in grade of dysplasia and change in LOH profile at 8 key microsatellite regions. Feasibility outcomes will include recruitment targets, compliance with the study protocol and adverse effects. A qualitative sub-study will explore patient experience and perception of the trial.Discussion: The current management options for patients with high-risk OED are limited and mostly include surgical resection and clinical surveillance. However, there remains little evidence whether surgery can effectively lead to a notable reduction in the risk of oral cancer development. Similarly, surveillance is associated with concerns regarding delayed diagnosis of OED progressing to malignancy. The SAVER trial provides an opportunity to investigate the effects of a repurposed, inexpensive and well-tolerated medication as a potential chemopreventive strategy for patients with high-risk OED. The clinical and biological findings of SAVER will inform the appropriateness, design and feasibility of a definitive phase III trial.Trial Registration: The trial is registered with the European Clinical Trials Database ( Eudra-CT 2018-000197-30 ). ( http://www.isrctn.com/ISRCTN12448611 ). The trial was prospectively registered on 24/04/2018. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the efficacy of Jiuwei Zhenxin Granules combined with sodium valproate sustained release tablets in the treatment of bipolar affective disorder in maintenance period. METHODS: Totally 92 patients with bipolar affective disorder admitted into Ningxia Ning' an Hospital from Jun. 2017 to Jun. 2020 were selected and divided into control group and research group via random number table, with 46 cases in each group. The control group was treated with sodium valproate sustained release tablets, while the research group was given Jiuwei Zhenxin Granules based on the control group, both groups were treated for 2 months. The clinical efficacy of two groups were observed, polysomnogram was used to detect the sleep quality, trail making test ( TMT) was used to evaluate the cognitive function, generic quality of life inventory ( GQL-LI) was used to assess the life quality; and adverse drug reactions during treatment were recorded. RESULTS: The clinical total effective rate of research group was 91. 30% ( 42/ 46), which was significantly higher than that of the control group ( 73. 91 %, 34/46), with statistically significant difference ( P 0.05) . CONCLUSIONS: The clinical effect of Jiuwei Zhenxin Granules combined with sodium valproate sustained release tablets in the treatment of bipolar affective disorder in maintenance period is remarkable, which can improve patients ' sleep quality, prolong nighttime sleep time and promote patients' cognitive function, with high safety, and can provide a reference scheme for clinical treatment of bipolar affective disorder in maintenance phase. [ABSTRACT FROM AUTHOR]

We conducted this meta-analysis to assess the effects of sodium valproate (VPA) monotherapy on blood liver enzymes in patients with epilepsy. PubMed, Web of Science, EBSCO, Cochrane Library, Wanfang, China national knowledge infrastructure databases were searched. Nine studies were included. Results showed: (1) The overall SMD for blood AST, ALT, and GGT levels of VPA monotherapy group versus control group were 0.70 (95% CI=0.31 to 1.09, Z=3.52, p=0.0004), 0.47 (95% CI=− 0.01 to 0.95, Z=1.91, p=0.06), 0.44 (95% CI=0.29 to 0.60, Z=5.55, p<0.00001), respectively. (2) In subgroup meta-analysis, increased blood AST and GGT levels were observed in epileptic minors (AST: total SMD=0.85, 95% CI=0.40 to 1.30, Z=3.69, p=0.0002; GGT: total SMD=0.46, 95% CI=0.29 to 0.63, Z=5.25, p<0.00001). Elevated blood ALT level was observed in Asian patients receiving VPA monotherapy (total SMD=0.70, 95% CI=0.51 to 0.90, Z=7.01, p<0.00001), and the early stage of VPA monotherapy (total SMD=0.93, 95% CI=0.57 to 1.29, Z=5.09, p<0.00001). Overall, our results indicated that blood AST and GGT were significantly increased in epileptic minors receiving VPA monotherapy. The elevation of blood ALT was observed in Asian patients and the early stage of VPA monotherapy. However, due to the small number of included studies, our results should be considered with caution. [ABSTRACT FROM AUTHOR]

Background: Acute mania causes many problems for the patient and others. Therefore, it is very important to eliminate the symptoms quickly. Objectives: The present study made the individual comparison of the therapeutic effects of sodium valproate combined with quetiapine or haloperidol as an add-on among patients with bipolar I disorder experiencing an episode of mania or mixed feature admitted to a Psychiatric Center in Tehran. Methods: The present study was a double-blind clinical randomized trial conducted on 36 patients. All patients were investigated by the Young Mania Rating Scale (YMRS). The study lasted six weeks in total (after raising drug dosage to the maximum level). We prescribed sodium valproate 15 mg/kg plus quetiapine 500 mg daily in one group and sodium valproate 15 mg/kg plus haloperidol 10 mg daily in the other group. In addition, an equivalent dosage of quetiapine and haloperidol was prescribed. This study used different data analysis methods such as Paired t test, ANOVA, and chi-square test. Results: The YMRS scores did not show any statistically significant difference between quetiapine and haloperidol receiving groups (P > 0.05). Conclusions: This paper argued that a combination of sodium valproate with either quetiapine or haloperidol could be effective in the management of acute mania or mixed bipolar I disorder to reduce the severity and duration of symptoms, although there was no statistically significant difference between the efficacy of these two pharmacological therapies. [ABSTRACT FROM AUTHOR]

Background/aim: Sleep deprivation disrupts prepulse inhibition of acoustic startle reflex and can be used to mimic psychosis in experimental animals. On the other hand, it is also a model for other disorders of sensory processing, including migraine. This study aims to assess the effects of sodium valproate, a drug that is used in a variety of neuropsychiatric disorders, on normal and disrupted sensorimotor gating in rats. Materials and methods: Sixty-two Wistar albino rats were randomly distributed into 8 groups. Subchronic and intraperitoneal sodium valproate were administrated to the sleep-deprived and nonsleep-deprived rats by either 50-100 or 200 mg/kg/day. Prepulse inhibition test and locomotor activity test were performed. Sleep deprivation induced by the modified multiple platform method. Results: Sleep deprivation impaired prepulse inhibition, decreased startle amplitude, and increased locomotor activity. Sodium valproate did not significantly alter prepulse inhibition and locomotor activity in nonsleep-deprived and sleep-deprived groups. On the other hand, all doses decreased locomotor activity in drug-treated groups, and low dose improved sensorimotor gating and startle amplitude after sleep deprivation. Conclusion: Low-dose sodium valproate improves sleep deprivation-disrupted sensorimotor gating, and this finding may rationalize the use of sodium valproate in psychotic states and other sensory processing disorders. Dose-dependent effects of sodium valproate on sensorimotor gating should be investigated in detail. [ABSTRACT FROM AUTHOR]

This study aimed to assess the national trends in anti-seizure medication (ASM) prescription in Chinese adult outpatients with epilepsy over a 6-year period from 2013 to 2018. Prescriptions for adult outpatients with epilepsy from hospitals in six major cities were extracted from the database of the Hospital Prescription Analysis Cooperative Project. Trends in the annual prescriptions and expenditure of ASM were analyzed. Prescription patterns (monotherapy or combination therapy) were also assessed. A total of 225,767 prescriptions from 60 hospitals were eligible and extracted for analysis. The number of ASM prescriptions increased from 28,360 in 2013 to 44,110 in 2018, and the corresponding cost increased from 9,452,990 Chinese Yuan (CNY) in 2013 to 14,627,865 CNY in 2018. The share of newer ASM use increased continuously, accounting for 56.75% of prescriptions and 85.03% of expenditure in 2018. The most frequently prescribed ASMs were sodium valproate and levetiracetam. The proportion of sodium valproate use decreased, while the proportion of levetiracetam use increased dramatically in terms of both ASM prescriptions and expenditure. Monotherapy was more frequent than combination therapy. The three most common combination therapies were sodium valproate/lamotrigine, levetiracetam/oxcarbazepine, and sodium valproate/levetiracetam. In summary, ASM use increased rapidly in terms of the number of ASM prescriptions and cost during the 6-year period, which raises concern regarding the rational use and pharma-economic profiles of ASMs. In place of valproate, levetiracetam became the most frequently used ASM. The development of ASM prescription is in line with therapy guidelines and reflects the current state of research in China.

Valproic acid/sodium valproate (VPA), a drug originally prescribed as an anticonvulsant, has been widely reported to act on epigenetic marks by inducing histone acetylation, affecting the DNA and histone methylation status, and altering the expression of transcription factors, thus leading to modulation of gene expression. All these epigenetic changes have been associated with chromatin remodeling effects. The present minireview briefly reports the main effects of VPA on chromatin and image analysis and Fourier transform infrared (FTIR) microspectroscopy in association with molecular biology methodological approaches to investigate the VPA-induced changes in chromatin structure and at the higher-order supraorganizational level.

Stevens-Johnson syndrome is a severe immune-mediated cutaneous reaction occurring due to exposure to certain drugs. Lamotrigine is an FDA approved drug used in the treatment of bipolar depression. When it is given concomitantly with sodium valproate, the risk of developing Stevens-Johnson syndrome increases. Here we present the report of a patient with bipolar depression who developed serious skin rashes while on lamotrigine and NSAID prescribed by a local doctor, who recovered after timely management. This case highlights the importance of following proper dosing, drug escalation regimen and managing drug interactions during lamotrigine therapy.

This study aimed to assess the national trends in anti-seizure medication (ASM) prescription in Chinese adult outpatients with epilepsy over a 6-year period from 2013 to 2018. Prescriptions for adult outpatients with epilepsy from hospitals in six major cities were extracted from the database of the Hospital Prescription Analysis Cooperative Project. Trends in the annual prescriptions and expenditure of ASM were analyzed. Prescription patterns (monotherapy or combination therapy) were also assessed. A total of 225,767 prescriptions from 60 hospitals were eligible and extracted for analysis. The number of ASM prescriptions increased from 28,360 in 2013 to 44,110 in 2018, and the corresponding cost increased from 9,452,990 Chinese Yuan (CNY) in 2013 to 14,627,865 CNY in 2018. The share of newer ASM use increased continuously, accounting for 56.75% of prescriptions and 85.03% of expenditure in 2018. The most frequently prescribed ASMs were sodium valproate and levetiracetam. The proportion of sodium valproate use decreased, while the proportion of levetiracetam use increased dramatically in terms of both ASM prescriptions and expenditure. Monotherapy was more frequent than combination therapy. The three most common combination therapies were sodium valproate/lamotrigine, levetiracetam/oxcarbazepine, and sodium valproate/levetiracetam. In summary, ASM use increased rapidly in terms of the number of ASM prescriptions and cost during the 6-year period, which raises concern regarding the rational use and pharma-economic profiles of ASMs. In place of valproate, levetiracetam became the most frequently used ASM. The development of ASM prescription is in line with therapy guidelines and reflects the current state of research in China. [ABSTRACT FROM AUTHOR]