Use Of Valproic Acid Research Articles

The hidden diagnosis: hypogonadotropic hypogonadism unveiled in a rare Fanconi syndrome case—a case report and literature review

Introduction and importance: Fanconi syndrome affects kidney function, whereas hypogonadotropic hypogonadism (HH) is gonadal failure due to deficient hormones. Diagnosis involves assays and imaging, whereas treatment targets cause and fluid balance. Here, there is a reported co-occurrence in Pakistan. Case presentation: A 14-year-old girl presented with joint pain and developmental delay. Physical examination revealed wrist widening, genu-varum, and underdeveloped secondary sexual characteristics. Laboratory findings confirmed Fanconi syndrome and coincidental ultrasound findings revealed HH. The patient received treatment in the form of oral medications and supplements to manage the condition. Clinical discussion: Fanconi syndrome is a complex disorder affecting the proximal tubule of the kidneys, leading to impaired reabsorption of various substances. In this case, potential genetic and acquired causes were ruled out, including inborn errors of metabolism and heavy metal intoxication. Prolonged valproic acid use was also considered but not confirmed as the cause. The patient also presented with HH, which is unrelated but coexisting. Treatment for Fanconi syndrome focuses on correcting electrolyte imbalances, whereas hormone replacement therapy is considered for HH. The patient’s progress and response to treatment are under careful monitoring. Conclusion: This case highlights the need for further research and comprehensive diagnostic evaluation to better understand the association between Fanconi syndrome and HH, emphasizing the importance of early diagnosis and management to prevent long-term complications.

Association Between Maternal Factors in Early Pregnancy and Congenital Heart Defects in Offspring: The Japan Environment and Children's Study.

Background Many prenatal factors are reported to be associated with congenital heart defects (CHD) in offspring. However, these associations have not been adequately examined using large-scale birth cohorts. Methods and Results We evaluated a data set of the Japan Environmental and Children's Study. The primary outcome was a diagnosis of CHD by age 2 years. We defined the following variables as exposures: maternal baseline characteristics, fertilization treatment, maternal history of diseases, socioeconomic status, maternal alcohol intake, smoking, tea consumption, maternal dietary intake, and maternal medications and supplements up to 12 weeks of gestation. We used multivariable logistic regression analysis to assess the associations between various exposures and CHD in offspring. A total of 91 664 singletons were included, among which 1264 (1.38%) had CHD. In multivariable analysis, vitamin A supplements (adjusted odds ratio [aOR], 5.78 [95% CI, 2.30-14.51]), maternal use of valproic acid (aOR, 4.86 [95% CI, 1.51-15.64]), maternal use of antihypertensive agents (aOR, 3.80 [95% CI, 1.74-8.29]), maternal age ≥40 years (aOR, 1.59 [95% CI, 1.14-2.20]), and high maternal hemoglobin concentration in the second trimester (aOR, 1.10 per g/dL [95% CI, 1.03-1.17]) were associated with CHD in offspring. Conclusions Using a Japanese large-scale birth cohort study, we found 6 maternal factors to be associated with CHD in offspring.

The antipsychotic olanzapine reduces memory deficits and neuronal abnormalities in a male rat model of Autism

The prevalence of autism spectrum disorder (ASD), a neurodevelopmental condition that impacts social interaction and sensory processing, is rising. Valproic acid (VPA) exposure during pregnancy causes autistic-like traits in offspring. Olanzapine (OLZ), an atypical antipsychotic, is used to treat ASD. We assessed the impact of OLZ on behavior, neuromorphology, and nitric oxide (NO) levels in the hippocampus using prenatal VPA treatment in rats. It is commonly known that ASD patients exhibit sensory abnormalities. As such, we utilized the tail flick test to validate the ASD model. In the novel object recognition test (NORT), VPA exposure reduces the discrimination index (DI) in the first introduction to the novel object. Moreover, OLZ and vehicle-treated rats perform differently in the second exposition to the DI of the novel object, suggesting that OLZ reverses VPA-induced deficits in recognition memory. The latency to find the hidden platform in the Morris water maze test of memory and learning improves in VPA-exposed rats after OLZ administration, indicating that OLZ improves spatial memory in these rats. Administration of prenatal VPA induces neuronal hypotrophy and reduces spine density in pyramidal neurons of the CA1 region of the hippocampus. Treatment with OLZ corrects the neuromorphological changes brought on by VPA. In the CA1 region of the hippocampus, VPA treatment increases the number of neurons, which normalizes with OLZ treatment. OLZ increases the NO levels in the dorsal hippocampus in control rats. In rats exposed to VPA, the second-generation antipsychotic OLZ reduces memory-related and neuroplastic alterations. The current findings support the use of OLZ in this illness and further validate the use of prenatal VPA as a model of ASD.

Birth Outcomes in Pregnant Women with Epilepsy: a Nationwide Multicenter Study from Türkiye.

The present study was aimed at investigating the effects of anti-seizure medications (ASMs), patient demographic characteristics, and the seizure type and frequency on the development of congenital malformation (CM) in infants of pregnant women with epilepsy (PWWE). PWWE followed-up at the neurology outpatient clinic of 21 centers between 2014 and 2019 were included in this prospective study. The follow-up of PWWE was conducted using structured, general pregnant follow-up forms prepared by the Pregnancy and Epilepsy Study Committee. The newborns were examined by a neonatologist at 1. and 3. months postpartum. Of the infants of 759 PWWE , 7.2% had CMs, with 5.6% having major CMs. Polytherapy, monotherapy, and no medications were received by 145 (19.1%), 517 (68.1%), and 42 patients, respectively. CMs were detected at an incidence of 2.3% in infants of those who did not receive medication, 5.7% in infants of those who received monotherapy, and 13.7% in infants of those who received polytherapy. The risk of malformation was 2.31-folds (95% confidence interval: 1.48-4.61, p < 0.001) higher in infants of PWWE who received polytherapy. Levetiracetam was the most frequently used seizure medication as monotherapy, with the highest incidence of CMs occurring with valproic acid (VPA) use (8.5%) and the lowest with lamotrigine use (2.1%). The incidence of CMs was 5% at a carbamazepine dose <700 mg, 10% at a carbamazepine dose ≥700 mg, 5.5% at a VPA dose <750 mg, and 14.8% at a VPA dose ≥750 mg. Thus, the risk of malformation increased 2.33 times ( p = 0.041) in infants of those receiving high-dose ASMs. Birth outcomes of PWWE receiving and not receiving ASMs were evaluated. The risk of CMs occurrence was higher, particularly in infants of PWWE using VPA and receiving polytherapy. The incidence of CMs was found to be lower in infants of PWWE receiving lamotrigine.

YouTube as a source of information on preventing the use of valproic acid in women during pregnancy

BackgroundYouTube™ (http://www.youtube.com), as a very popular video site worldwide, is increasingly being used as a platform to disseminate health information. The purposes of this review were to assess the overall usefulness of the information on the prevention of valproic acid use in women during pregnancy on YouTube™ for patients.MethodsThe YouTube™ website was systematically using 8 keywords. One hundred and fifty four videos meet the selection criteria. The researcher evaluated the video duration, days since upload, views and the likes. These videos are categorized as Education, News & Politics and People & Blogs. We designed a usefulness scoring scheme to assess videos quality and classified them as “slightly useful”, “useful” and “very useful”. The Kruskal-Wallis test was used to determine whether differences existed between total usefulness scores and categories and Pearson chi-square test for categorical variables.ResultsThe majority of videos were educational (62.8%). The "People & Blogs" and "News & Politics" videos scored significantly higher, but had no significant difference in days since upload, views, views/day or likes. More than half of the videos (91/154) were categorized as “useful”. The mean posted days (p = 0.045) was significantly different in the useful group compared with the slightly useful group. There were no correlation between usefulness and the number of days since upload, duration, views, views/day, or likes.ConclusionYouTube™ is a promising source of information regarding the use of valproic acid during pregnancy. "News & Politics" videos are the most usefulness. Considering the presence of more slightly useful information, publishers need to improve more comprehensive video content that includes replacement medications, diagnoses and treatments. In the healthcare information space, consumers need to be directed to reliable video.

Relationship Between Cleft Lip and Palate Followed by Osteogenesis Imperfecta Accompanied by Tetralogy of Fallot in Children with a Maternal History of Catatonic Schizophrenia with Valproic Acid Therapy and Diabetes Mellitus

Researchers believe that most cases of cleft lip and cleft palate are caused by genetic and environmental factors. Nevertheless, the exact cause was not found. Nevertheless there are allegations that the condition of the cleft lip and palate has something to do with osteogenesis imperfecta with the heterozygous mutation COL1A2 and the formation of triple helix DNA accompanied by Tetralogy of Fallot in children with a maternal history of catatonic schizophrenia followed by the use of valproic acid and type II diabetes mellitus. Then, it is also found in babies with cleft lip and sky conditions usually accompanied by other congenital anomaly, but not always. This then further gives rise to speculation that there are links between the above variables and the cleft lip and palate. Therefore. Knowing the Relationship Between Cleft Lip and Palate Events with osteogenesis imperfecta with heterozygous mutation COL1A2 and triple helix DNA formation accompanied by Tetralogy of Fallot in children with a maternal history of catatonic schizophrenia followed by the use of valproic acid and type II diabetes mellitus. This research is a Systematic Review using the Preferred Reporting Items for Systematic Reviews and Meta-analyses method or commonly called PRISMA, this method is carried out systematically by following the correct research stages or protocols. The source was taken from the Google Scholar site with journals published in 2017-2023 and then screened the results of 1,870 journals. Journal clustering was carried out and the number of Q1 indexed journals was obtained in 4 journals, Q3 in 1 journal, and Q4 in 1 journal so that there were 6 journals extracted. The entire journal does not directly discuss the relationship between the research variables, but only provides an overview of the increased risk of celestial cleft conditions in babies if the expectant mother has type 2 diabetes mellitus conditions, osteogenesis imperfect, and the relationship of the two health conditions to the possibility of birth of the baby with the Tetralogy of Fallot condition, as well as the relationship of the baby to the condition of the cleft lip and palate and tetralogy of fallot

Valproate-Induced Metabolic Syndrome.

Valproic acid (VPA) and its salts (sodium calcium magnesium and orotic) are psychotropic drugs that are widely used in neurology and psychiatry. The long-term use of VPA increases the risk of developing adverse drug reactions (ADRs), among which metabolic syndrome (MetS) plays a special role. MetS belongs to a cluster of metabolic conditions such as abdominal obesity, high blood pressure, high blood glucose, high serum triglycerides, and low serum high-density lipoprotein. Valproate-induced MetS (VPA-MetS) is a common ADR that needs an updated multidisciplinary approach to its prevention and diagnosis. In this review, we consider the results of studies of blood (serum and plasma) and the urinary biomarkers of VPA-MetS. These metabolic biomarkers may provide the key to the development of a new multidisciplinary personalized strategy for the prevention and diagnosis of VPA-MetS in patients with neurological diseases, psychiatric disorders, and addiction diseases.

Endoscopic ultrasound-guided cystogastrostomy in the treatment of the complicated form of acute pancreatitis in children

Acute pancreatitis is relatively rare in children, with approximately 313 cases per 100,000 populations annually, and complicated forms are three times less common than those in adults. However, recently, the number of acute pancreatitis cases in children has increased, which entails a relatively higher incidence of complicated acute pancreatitis, including parapancreatic acute fluid accumulation, and determines the relevance of this problem for pediatric surgeons.&#x0D; In this study, using two sample observations, parapancreatic pseudocyst puncture under ultrasound and X-ray control was presented, a conductor string was introduced into the cavity of the pseudocyst, and further stenting of this anastomosis was performed with two plastic double-pigtail stents. In the first case, a 12-year-old boy underwent surgery for idiopathic pancreatitis and acute parapancreatic fluid accumulation in the pancreatic tail. In the second case, a 10-year-old girl presented with a parapancreatic pseudocyst, which was caused by drug-induced pancreatitis (a complication of the long-term use of valproic acid, an antiepileptic drug). Both children underwent surgery using this technique. Antisecretory therapy was performed postoperatively. In the catamnesis after 1 year and 6 months, the children had no complaints, and ultrasound and X-ray studies did not reveal any pathology. Endoscopic cystogastrostomy under ultrasound guidance is widely performed in complicated pancreatitis in adults. These observations show its effectiveness in pediatric practice. However, the relatively short observation period of treatment results requires additional research on a much larger number of cases and outcomes of these surgical interventions in children.

Treating Bipolar Disorder in Older Adults Tricky, but Manageable

Treating Bipolar Disorder in Older Adults Tricky, but Manageable

Therapeutic Drug Monitoring of Perampanel in Children With Refractory Epilepsy: Focus on Influencing Factors on the Free-Perampanel Concentration.

This study aimed to assess the effect of perampanel dose, age, sex, and antiseizure medication cotherapy on steady-state free-perampanel concentration in children with refractory epilepsy, as well as the relationship between inflammation and the pharmacokinetics of perampanel. This prospective study in China included 87 children with refractory epilepsy treated with adjunctive perampanel therapy. Free and total perampanel concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Free-perampanel concentration was compared among patients with various potential influencing factors. A total of 87 pediatric patients (44 female children) aged 2-14 years were enrolled. The mean free-perampanel concentration and free concentration-to-dose (CD) ratio in plasma were 5.7 ± 2.7 ng/mL (16.3 ± 7.7 nmol/L) and 45.3 ± 21.0 (ng/mL)/(mg/kg) [129.6 ± 60.1 (nmol/L)/(mg/kg)], respectively. The protein binding of perampanel in plasma was 97.98%. A linear relationship was observed between perampanel dose and free concentration in plasma, and a positive relationship was found between the total and free-perampanel concentrations. Concomitant use of oxcarbazepine reduced the free CD ratio by 37%. Concomitant use of valproic acid increased the free CD ratio by 52%. Five patients had a plasma high-sensitivity C-reactive protein (Hs-CRP) level of >5.0 mg/L (Hs-CRP positive). The total and free CD ratios of perampanel were increased in patients with inflammation. Two patients with inflammation developed adverse events, which disappeared as the Hs-CRP level returned to normal, and neither required perampanel dose reduction. Age and sex did not influence the free-perampanel concentration. This study found complex drug interactions between perampanel and other concomitant antiseizure medications, providing valuable information to enable clinicians to apply perampanel in the future reasonably. In addition, it may be important to quantify both the total and free concentrations of perampanel to assess complex pharmacokinetic interactions.

Risk of delirium with antiepileptic drug use: a study based on the Japanese Adverse Drug Event Report database.

Antiepileptic drugs may cause delirium, and the risk may vary with each drug. However, related studies have provided inconsistent results. The aim of this study was to investigate whether the use of antiepileptic drugs is a risk factor for delirium development. Using the Japanese Adverse Drug Event Report database, we analysed 573,316 reports pertaining to the period from 2004 to 2020. Reporting odds ratios and 95% confidence intervals of delirium associated with use of antiepileptic drugs were calculated after adjusting for potential confounders. Furthermore, for each antiepileptic drug, we performed an analysis stratified based on older age and benzodiazepine receptor agonist usage. There were 27,439 reports of antiepileptic drug-related adverse events. Of these, 191 reports were associated with antiepileptic drugs and delirium (crude reporting odds ratio [cROR], 1.66; 95% confidence interval [CI], 1.43-1.93). The use of lacosamide (adjusted reporting odds ratio [aROR], 2.44; 95% CI, 1.24-4.80), lamotrigine (aROR, 1.54; 95% CI, 1.05-2.26), levetiracetam (aROR, 1.91; 95% CI, 1.35-2.71), and valproic acid (aROR, 1.49; 95% CI, 1.16-1.91) was related to a significantly higher reporting odds ratio for delirium, even after adjustment for possible confounding factors. However, when used in combination with benzodiazepine receptor agonists, none of the antiepileptic drugs were found to be associated with delirium. Our study's findings suggest that antiepileptic drug usage may be associated with delirium development.

A Retrospective Case Series on Valproic Acid for Early Post-Traumatic Seizure Prophylaxis After Traumatic Brain Injury in Patients With Concomitant Agitation.

Purpose: Early post-traumatic seizures occur within 7 days following a traumatic brain injury and may lead to additional brain damage and poor outcomes. Levetiracetam or phenytoin is often used for seizure prophylaxis in this patient population, but valproic acid may be an appropriate therapeutic alternative in patients with concomitant agitation. Evidence for the use of valproic acid for both early post-traumatic seizure prophylaxis and agitation is limited. The purpose of this study is to examine the safety and efficacy of valproic acid for both early post-traumatic seizure prophylaxis and agitation. Methods: This single-center, retrospective case series includes 18 patients who received valproic acid for both early post-traumatic seizure prophylaxis and agitation. Efficacy for early post-traumatic seizure prophylaxis is assessed by the incidence of seizures within 7 days of injury. Efficacy for agitation is assessed by changes in Riker Sedation-Agitation Scale scores during valproic acid therapy. The safety of valproic acid is defined by the incidence of selected adverse events. Results: Among 18 patients with traumatic brain injuries receiving valproic acid for both early post-traumatic seizures and agitation, one patient experienced a seizure during the period of prophylaxis and thrombocytopenia was the most common adverse event. Conclusion: In this small cohort of patients, valproic acid appears be a potential option to prevent early post-traumatic seizures in patients with traumatic brain injuries and concomitant agitation with minimal adverse effects. Randomized, controlled studies are needed to further investigate the role of valproic acid for this indication, including standards for dosing regimens, serum drug monitoring, and the relationship between valproic acid treatment and mortality.

Impact of regulatory restrictions on the use of valproic acid in women of childbearing age: An Italian study.

Due to significant risks to the offspring after intrauterine exposure, the European Medicines Agency issued recommendations in 2014 and 2018 restricting the use of valproate (VPA) in women of childbearing age (WOCA). We aimed to evaluate their impact in the Emilia-Romagna region (ERR) of Northern Italy. Using administrative databases, we identified all the ERR residents who received antiseizure medication (ASM) prescriptions from 2010 to 2020. Time series of incidence rates by sex and age group were evaluated for all ASMs. Focusing on VPA, an interrupted time series analysis was applied to assess the impact of the restrictions in WOCA with epilepsy (WOCA-E) and WOCA with psychiatric disorders (WOCA-P). We then evaluated the chronological order of ASM prescriptions with regard to the position of VPA. Incidence rates of VPA prescriptions overall decreased over time. A significant decrease was observed only for females. The effect was stronger for WOCA, after both the first (incidence rate ratio [IRR]=.85, 95% confidence interval [CI]=.75-.96) and the second restriction (IRR=.67, 95% CI=.55-.82). The decrease was significant after the second restriction both for WOCA-E (IRR=.43, 95% CI=.27-.68) and for WOCA-P (IRR=.49, 95% CI=.35-.70), as well as VPA as a first prescription in both populations. VPA prescriptions as further choice did not show the same trend. After the regulatory restrictions, an overall significant decline in the use of VPA in WOCA was observed in ERR. The second restriction has been effective in consolidating the prescription trend. However, VPA appears still to be a commonly used drug in WOCA when other ASMs have failed.

Combination of metformin and sub-therapeutic dose of valproic acid prevent valproic acid-induced toxicity in animal model of epilepsy

Valproic acid (VPA) is one of the most prescribed drugs for epilepsy. Extended use of VPA not only induces hepatotoxicity but also impairs the cognitive functions. Metformin has been reported to prevent epileptogenesis and enhance memory. To counter the VPA-induced adverse events, it is hypothesized that combination of sub-therapeutic dose of VPA with metformin may attenuate the toxicity stemming from the therapeutic dose of VPA. Pentylenetetrazole (PTZ)-induced kindling model of epilepsy in mice was used to assess the combined effects of sub-therapeutic dose of VPA (100 mg/kg) and metformin (200 mg/kg). The memory performance was analyzed by passive avoidance test, while alkaline comet assay was used to determine genotoxicity. Histopathological examination and serum biochemical analysis was performed to determine hepatotoxicity. Results showed that combination dose of VPA with metformin reduced seizure scores. VPA (300 mg/kg) administered as a single agent did not enhance memory impairment caused by PTZ, however, combination of sub-therapeutic dose of VPA with metformin enhanced memory function. Furthermore, in alkaline comet assay, combination therapy demonstrated reduced genotoxicity compared to the VPA 300 mg/kg. Histopathological examination of liver and analysis of serum hepatic enzymes revealed that combination therapy (VPA + metformin) reversed the toxicity as seen in case of PTZ or VPA (300 mg/kg) treated animals with no other treatment given. Based on the study data, it is concluded that the combination of sub-therapeutic dose of VPA with metformin might be used for epileptic seizures. This will prevent the hepatotoxicity and enhanced memory functions as compared to the VPA given as a single agent therapy.

A curious case of confusion

A curious case of confusion

Sex differences in variables associated with excessive daytime sleepiness in patients with epilepsy

ObjectiveExcessive daytime sleepiness (EDS) is common in patients with epilepsy (PWE). The Epworth Sleepiness Scale (ESS) is a self-reported measure of sleepiness in widespread use. The purpose of this study was to identify contributors to the ESS score in PWE and to identify variables associated with a high score indicative of EDS. MethodsA cross-sectional study was performed on 115 PWE presenting to the epilepsy clinic. Self-reported questionnaires were administered and demographic and clinical information was gathered from the electronic medical record. Regression analyses were performed. ResultsA high ESS score was found in nearly 20% of the cohort. Obstructive sleep apnea (OSA) risk, standardized anti-seizure drug (ASD) dose, and female sex were associated with an increased likelihood of a high ESS score. Assessment of the ESS without the use of a cutpoint showed that standardized ASD dose and OSA risk were associated with the ESS in men, but standardized ASD dose was not associated with the ESS in women. Higher use of valproic acid and oxcarbazepine in men and higher use of lamotrigine in women may be contributing factors. SignificanceSex is likely to be a key factor in determining contributors to EDS in PWE.

Valproic acid-induced hyperammonemia in neuropsychiatric disorders: a 2-year clinical survey.

Valproic acid (VPA)-induced hyperammonemia (HA) is a rare adverse effect reported even at therapeutic VPA levels. The present study aimed to investigate the characteristics of VPA-induced HA and its association with the total dose, duration, and level of VPA. This study also investigated whether the use of VPA in combination with other medications has any effect on elevating serum ammonia levels. A total of 316 patients with a history of VPA prescribed for underlying neuropsychiatric disorders were found eligible for the study. Data including demographic information, medical history and diagnosis, VPA dosage, VPA treatment duration, VPA level, and ammonia serum level were extracted and reviewed from our hospital records. The history of other neuropsychiatric medications was also included. Among 316 patients receiving VPA, HA was observed in 54 (17%) patients, and 15 patients were symptomatic among them. There was no significant difference in demographics between symptomatic and asymptomatic HA groups except for the number of co-administrated medications (p = 0.044). Besides, VPA duration and dose did not show a significant difference between the two groups. Additionally, the VPA level was significantly higher in patients who used risperidone in addition to VPA (p = 0.019). Eventually, VPA level showed a significant association with ammonia level (p = 0.025) and symptomatic HA (p = 0.033) after adjusting for possible confounders. VPA level showed a significant association with ammonia level and symptomatic HA. Moreover, co-administrated medications such as risperidone might have an impact on the serum level of VPA. Further studies are recommended to confirm these findings.

The effect of valproic acid and furosemide on the regulation of the inflammasome complex (NLRP1 and NLRP3 mRNA) in the brain of epileptic animal model

ObjectivesThis study aimed to explore the effect of concomitant use of Furosemide (FRS) and Valproic acid (VPA), demonstrating anti-inflammation efficacy, on epilepsy, and its underlying mechanism. MethodsTwenty-five adult male Wistar rats were divided into five groups including, Group 1: (Normal) rats received no drugs, Group 2: (E): rats were administered with a single dose of kainic acid (stereotaxic surgery), Group 3: (E + VPA): rats received Valproic acid (200 mg/kg/day/orally), Group 4: (E + FRS): rats received a single dose of Furosemide (100 mg/kg/I.P.) 30 min before epilepsy induction, Group 5: (E + VPA (200 mg/Kg)+FRS (100 mg/Kg, combination treatment). The treatment group received VPA for 14 days. We assessed seizures based on modified Racine΄s scores and conducted the electroencephalographic (EEG) recording. NLRP1 and NLRP3 mRNA levels, Apoptosis-associated Speck-like protein containing a caspase recruitment domain (ASC), absence in melanoma2 (AIM2) protein expression levels, and apoptosis rate of the brain cells were analyzed utilizing real-time PCR, immunohistochemistry, and tunnel assay, respectively. ResultsThe results revealed that FRS and VPA treatment, alone or in combination, improved behavioral outcome and reduced seizure intensity in epileptic rats. The combination therapy significantly decreased the apoptosis rate NLRP1 and NLRP3 gene as well as ASC and AIM2 protein expression levels. ConclusionCombination therapy protected the brain against neuronal damages in rats, and decreased the severity of epilepsy in K.A. induced rats. Reducing inflammation and apoptosis and improving the performance of behavioral testing in the K.A. induced epilepsy model increased the likelihood of success of combination therapy compared with VPA and FRS treatment alone.

The influence of continuous prenatal exposure to valproic acid on physical, nociceptive, emotional and psychomotor responses during adolescence in mice: Dose-related effects within sexes.

Clinical findings show that the use of valproic acid (VPA) during pregnancy increases the risk of birth defects and autism spectrum disorder in offspring. Although there is a consensus that monitoring of potential long-term outcomes of VPA exposure is needed, especially in undiagnosed individuals, preclinical studies addressing this issue are rare. The present study examined the effects of continuous intrauterine exposure to a wide dose range of VPA (50, 100, 200, and 400 mg/kg/day) on the physical and behavioral response in peripubertal mice as a rodent model of adolescence. Body weight and the hot plate test [on postnatal days (PND) 25 and 32], the elevated plus-maze test (on PND35), and the open field test (on PND40) served to examine physical growth, the supraspinal reflex response to a painful thermal stimulus and conditional learning, anxiety-like/risk-assessment behavior, as well as novelty-induced psychomotor activity, respectively. VPA exposure produced the following responses: (i) a negative effect on body weight, except for the dose of 100 mg/kg/day in both sexes; (ii) an increase in the percentage of animals that responded to the thermal stimulus above the defined cut-off time interval and the response latency in both sexes; (iii) dose-specific changes within sexes in behavior provoked by a novel anxiogenic environment, i.e., in females less anxiety-like/risk-assessment behavior in response to the lowest exposure dose, and in males more pronounced anxiety-like/risk-assessment behavior after exposure to the highest dose and 100 mg/kg/day; (iv) dose-specific changes within sexes in novelty-induced psychomotor activity, i.e., in females a decrease in stereotypy-like activity along with an increase in rearing, and in males a decrease in stereotypy-like activity only. These findings show that continuous intrauterine exposure to VPA produces maladaptive functioning in different behavioral domains in adolescence and that the consequences are delicate to assess as they are dose-related within sexes.

Use of Valproic Acid for the Management of Delirium and Agitation in the Intensive Care Unit

Purpose: Assess the efficacy and safety of valproic acid (VPA) for delirium and agitation in the intensive care unit (ICU) as compared to the use of other antipsychotics. Materials and Methods: This was a retrospective cohort study of patients treated for delirium and agitation in the ICU. Patients were included if they had a Richmond Agitation-Sedation Scale ≥2 and Confusion Assessment Method for the ICU positive. Patients were split into two groups based on their VPA exposure. The primary outcome was delirium free days. Secondary outcomes included agitation free days, ICU length of stay (LOS), mechanical ventilation duration, and mortality. Results: One hundred eight patients were included, 49 patients in the VPA group and 59 patients in the control group. Baseline characteristics were similar between groups. There was no significant difference in the primary outcome (difference −.15, 95% CI: 0.63-.93, P = .70). There were no significant differences in agitation-free days, mortality, mechanical ventilation duration, or ICU LOS. Conclusions: Our findings suggest that VPA is associated with similar delirium and agitation-free days compared to other non-VPA medications, with some adverse effects. Larger prospective studies are needed to validate the routine use of VPA in this setting.