Use Of Valproate Research Articles

Absolute and Relative Risks of Kidney Outcomes Associated With Lithium vs Valproate Use in Sweden

Among patients with bipolar disorder, discordant findings have been published on the nephrotoxic effects of lithium therapy. To quantify absolute and relative risks of chronic kidney disease (CKD) progression and acute kidney injury (AKI) in people who initiated lithium compared with valproate therapy and to investigate the association between cumulative use and elevated lithium levels and kidney outcomes. This cohort study had a new-user active-comparator design and used inverse probability of treatment weights to minimize confounding. Included patients initiated therapy with lithium or valproate from January 1, 2007, to December 31, 2018, and had a median follow-up of 4.5 years (IQR, 1.9-8.0 years). Data analysis began in September 2021, using routine health care data from the period 2006 to 2019 from the Stockholm Creatinine Measurements project, a recurrent health care use cohort of all adult residents in Stockholm, Sweden. New use of lithium vs new use of valproate and high (>1.0 mmol/L) vs low serum lithium levels. Progression of CKD (composite of >30% decrease relative to baseline estimated glomerular filtration rate [eGFR] and kidney failure), AKI (by diagnosis or transient creatinine elevations), new albuminuria, and annual eGFR decrease. Outcomes by attained lithium levels were also compared in lithium users. The study included 10 946 people (median [IQR] age, 45 [32-59] years; 6227 female [56.9%]), of whom 5308 initiated lithium therapy and 5638 valproate therapy. During follow-up, 421 CKD progression events and 770 AKI events were identified. Compared with patients who received valproate, those who received lithium did not have increased risk of CKD (hazard ratio [HR], 1.11 [95% CI, 0.86-1.45]) or AKI (HR, 0.88 [95% CI, 0.70-1.10]). Absolute 10-year CKD risks were low and similar: 8.4% in the lithium group and 8.2% in the valproate group. No difference in the risk of developing albuminuria or the annual rate of eGFR decrease was found between groups. Among more than 35 000 routine lithium tests, only 3% of results were in the toxic range (>1.0 mmol/L). Lithium values greater than 1.0 mmol/L, compared with lithium values of 1.0 mmol/L or less, were associated with increased risk of CKD progression (HR, 2.86; 95% CI, 0.97-8.45) and AKI (HR, 3.51; 95% CI, 1.41-8.76). In this cohort study, compared with new use of valproate, new use of lithium was meaningfully associated with adverse kidney outcomes, with low absolute risks that did not differ between therapies. However, elevated serum lithium levels were associated with future kidney risks, particularly AKI, emphasizing the need for close monitoring and lithium dose adjustment.

Valproate pregnancy prevention scheme: what are the barriers to enrolling patients and how do we meet them?

BackgroundThe UK Medicines Health products Regulation Agency instructs that valproate prescriptions should be restricted in women of childbearing age to those consenting to the Pregnancy Prevention Programme (PPP). We assessed...

3P's (Pharmacokinetic, Pharmacodynamic, and Pharmacogenomic) of Valproate: What's New?

Valproate (VPA) has been used clinically for more than 40 years and remains one of the most commonly prescribed antiepileptic drugs. With the advances of various scientific disciplines, much new information about this drug has been uncovered. The aim of this review is to summarize new knowledge about the pharmacokinetics, pharmacodynamics, and pharmacogenomics (3Ps) of VPA for future applications and studies. The review was identified nonsystematically using Pubmed, Google Scholar, and open-access search engines, and studies on the pharmacokinetics, pharmacodynamics, and pharmacogenomics of VPA between 2012 and 2022 were included. Recent findings on pharmacokinetic information, including factors associated with serum VPA levels and its interaction with new drugs. On the other hand, VPA was found to have a neuroprotective effect that is beneficial in brain disorders as well as in patients with c stroke. With respect to the lungs, it has been found to reduce the risk of acute respiratory failure. Recent risk data linked VPA use to hepatotoxicity, vitamin D deficiency, prolonged QT interval, and insulin resistance, among others. Various gene polymorphisms such as CYP2C9 and UGT1A6 are some polymorphisms that may cause dose alteration in the population. The compilation of the 3Ps of VPA revealed new drug information indicating the need for further evaluation. These include new uses and benefits, toxicity data including acute and chronic use, and the involvement of genetic polymorphisms in the pharmacokinetics and pharmacodynamics of the drug.

Impact of 2018 EU Risk Minimisation Measures and Revised Pregnancy Prevention Programme on Utilisation and Prescribing Trends of Medicinal Products Containing Valproate: An Interrupted Time Series Study.

Due to established teratogenicity of valproates, the EU risk minimisation measures (RMMs) with a pregnancy prevention programme (PPP) for valproate were updated in March 2018. To investigate the effectiveness of the 2018 EU RMMs on valproate utilisation in five European countries/regions. A multi-database, times series study of females of childbearing potential (12-55 years) was conducted using electronic medical records from five countries/regions (01.01.2010-31.12.2020): Denmark, Tuscany (Italy), Spain, the Netherlands, and the UK. Clinical and demographic information from each database was transformed to the ConcePTION Common Data Model, quality checks were conducted and a distributed analysis was performed using common scripts. Incident and prevalent use of valproate, proportion of discontinuers and switchers to alternative medicine, frequency of contraception coverage during valproate use, and occurrence of pregnancies during valproate exposure were estimated per month. Interrupted time series analyses were conducted to estimate the level or trend change in the outcome measures. We included 69,533 valproate users from 9,699,371 females of childbearing potential from the five participating centres. A significant decline in prevalent use of valproates was observed in Tuscany, Italy (mean difference post-intervention -7.7%), Spain (-11.3%), and UK (-5.9%) and a non-significant decline in the Netherlands (-3.3%), but no decline in incident use after the 2018 RMMs compared to the period before. The monthly proportion of compliant valproate prescriptions/dispensings with a contraceptive coverage was low (<25%), with an increase after the 2018 RMMs only in the Netherlands (mean difference post-intervention 12%). There was no significant increase in switching rates from valproates to alternative medicine after the 2018 intervention in any of the countries/regions. We observed a substantial number of concurrent pregnancies during valproate exposure, but with a declining rate after the 2018 RMMs in Tuscany, Italy (0.70 per 1000 valproate users pre- and 0.27 post-intervention), Spain (0.48 and 0.13), the Netherlands (0.34 and 0.00), and an increasing rate in UK (1.13 and 5.07). There was a small impact of the 2018 RMMs on valproate use in the studied European countries/regions. The substantial number of concurrent pregnancies with valproate exposure warrants a careful monitoring of implementation of the existing PPP for valproate in clinical practice in Europe, to see if there is any need for additional measures in the future.

Prenatal Exposure to Antiseizure Medication and Incidence of Childhood- and Adolescence-Onset Psychiatric Disorders

Prenatal antiseizure medication (ASM) exposure has been associated with adverse early neurodevelopment, but associations with a wider range of psychiatric end points have not been studied. To examine the association between prenatal exposure to ASM with a spectrum of psychiatric disorders in childhood and adolescence in children of mothers with epilepsy. This prospective, population-based register study assessed 4 546 605 singleton children born alive in Denmark, Finland, Iceland, Norway, and Sweden from January 1, 1996, to December 31, 2017. Of the 4 546 605 children, 54 953 with chromosomal disorders or uncertain birth characteristics were excluded, and 38 661 children of mothers with epilepsy were identified. Data analysis was performed from August 2021 to January 2023. Prenatal exposure to ASM was defined as maternal prescription fills from 30 days before the first day of the last menstrual period until birth. The main outcome measure was diagnosis of psychiatric disorders (a combined end point and 13 individual disorders). Estimated adjusted hazard ratios (aHRs) using Cox proportional hazards regression and cumulative incidences with 95% CIs are reported. Among the 38 661 children of mothers with epilepsy (16 458 [42.6%] exposed to ASM; 19 582 [51.3%] male; mean [SD] age at the end of study, 7.5 [4.6] years), prenatal valproate exposure was associated with an increased risk of the combined psychiatric end point (aHR, 1.80 [95% CI, 1.60-2.03]; cumulative risk at 18 years in ASM-exposed children, 42.1% [95% CI, 38.2%-45.8%]; cumulative risk at 18 years in unexposed children, 31.3% [95% CI, 28.9%-33.6%]), which was driven mainly by disorders within the neurodevelopmental spectrum. Prenatal exposure to lamotrigine, carbamazepine, and oxcarbazepine was not associated with an increased risk of psychiatric disorders, whereas associations were found for prenatal exposure to topiramate with attention-deficit/hyperactivity disorder (aHR, 2.38; 95% CI, 1.40-4.06) and exposure to levetiracetam with anxiety (aHR, 2.17; 95% CI, 1.26-3.72) and attention-deficit/hyperactivity disorder (aHR, 1.78; 95% CI, 1.03-3.07). Findings from this explorative study strengthen the evidence for the warning against the use of valproate in pregnancy and raise concern of risks of specific psychiatric disorders associated with topiramate and levetiracetam. This study provides reassuring evidence that lamotrigine, carbamazepine, and oxcarbazepine are not associated with long-term behavioral or developmental disorders but cannot rule out risks with higher doses.

How accurately do adult patients report their absence seizures?

We depend upon self-reporting to determine seizure frequency for epilepsy management decisions, but people often misreport their seizures. Here, we determined misreporting rates in adults with absence seizures, undergoing inpatient video-EEG telemetry (VET) or outpatient ambulatory electroencephalography (aEEG). Under-reporting rates were based on VET data, where behavior could be assessed, whilst over-reporting was assessed using both VET and aEEG. Forty-two patients (31 female and 11 males, median age 28.5 years) and 759 reported absence seizures were included in this study. Overall, only 24% of the 759 reported seizures had an associated EEG correlate, indicating a high over-reporting rate, which occurred in 57% of patients. Age, sex, time of epilepsy, VET versus aEEG, epilepsy syndrome, or medication were not significant predictors of over-reporting. In the VET group in which we could assess both over- and under-reporting (22 patients), only 2 patients correctly reported their seizures, and patients were predominantly over-reporters or under-reporters, not both. Only 26% of 423 absence seizures were reported. Use of zonisamide or valproate was associated with under-reporting, possibly through an impact on attention. These findings indicate that self-reported absence seizures are a poor measure to use for treatment decisions due to both over- and under-reporting.

A pilot study on the effects of early use of valproate sodium on neuroinflammation after traumatic brain injury

To study the effect of early use of sodium valproate on neuroinflammation after traumatic brain injury (TBI). A total of 45 children who visited in Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from August 2021 to August 2022 were enrolled in this prospective study, among whom 15 healthy children served as the healthy control group, and 30 children with TBI were divided into a sodium valproate treatment group and a conventional treatment group using a random number table (n=15 each). The children in the sodium valproate treatment group were given sodium valproate in addition to conventional treatment, and those in the conventional group were given an equal volume of 5% glucose solution in addition to conventional treatment. The serum concentrations of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), high-mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were measured in the healthy control group on the day of physical examination and in the children with TBI on days 1, 3, and 5 after admission. Glasgow Outcome Scale-Extended (GOS-E) score was evaluated for the children with TBI 2 months after discharge. Compared with the healthy control group, the children with TBI had significantly higher serum concentrations of NLRP3, HMGB1, TNF-α, and IL-1β on day 1 after admission (P<0.017). The concentration of NLRP3 on day 5 after admission was significantly higher than that on days 1 and 3 after admission in the children with TBI (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of NLRP3 than the conventional treatment group (P<0.05). For the conventional treatment group, there was no significant difference in the concentration of HMGB1 on days 1, 3, and 5 after admission (P>0.017), while for the sodium valproate treatment group, the concentration of HMGB1 on day 5 after admission was significantly lower than that on days 1 and 3 after admission (P<0.017). On day 5 after admission, the sodium valproate treatment group had a significantly lower concentration of HMGB1 than the conventional treatment group (P<0.05). For the children with TBI, the concentration of TNF-α on day 1 after admission was significantly lower than that on days 3 and 5 after admission (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of TNF-α than the conventional treatment group (P<0.05). The concentration of IL-1β on day 3 after admission was significantly lower than that on days 1 and 5 after admission (P<0.017) in the children with TBI. On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of IL-1β than the conventional treatment group (P<0.05). The GOS-E score was significantly higher in the sodium valproate treatment group than that in the conventional treatment group 2 months after discharge (P<0.05). Early use of sodium valproate can reduce the release of neuroinflammatory factors and improve the prognosis of children with TBI.

Valproate-related neutropenia and lithium-related leukocytosis in patients treated with clozapine: a retrospective cohort study

BackgroundNeutropenia is a noteworthy side effect of clozapine, which might warrant this drugs’ discontinuance for safety. Studies have revealed that the risk of neutropenia increases with concurrent administration of valproate, but the evidence was limited. Conversely, lithium may have an ameliorating effect on clozapine-induced neutropenia. This study explored the effects of valproate and lithium on white blood cell counts in patients treated with clozapine.MethodsWe retrospectively investigated the electronic medical records from one tertiary psychiatric hospital in Taiwan and enrolled patients discharged between January 1, 2006, and December 31, 2017, with clozapine prescriptions. We scrutinized their demographic data, medications, and hematological results at discharge and during follow-up outpatient clinic visits over the subsequent 3 years. Patients were classified into four groups: clozapine only (CLO), clozapine and valproate (CLO + VAL), clozapine and lithium (CLO + Li), and clozapine, valproate, and lithium (CLO + VAL + Li). We also identified hematological events (neutropenia or leukocytosis) of these patients during outpatient follow-ups.ResultsOf the included 1084 patients, 55(5.1%) developed neutropenia. Concurrent valproate use (odds ratio [OR] = 3.49) and older age (p = .007) were identified as risk factors. Moreover, 453 (41.79%) patients developed leukocytosis. Younger age; male sex; and concurrent use of lithium (OR = 3.39, p < .001), clozapine daily dosage, and benzodiazepines were the risk factors for leukocytosis.ConclusionConcurrent valproate use and older age are associated with the development of neutropenia in patients treated with clozapine. Concurrent lithium usage, younger age, male sex, and concurrent benzodiazepine use might be related to leukocytosis.

Valproate-induced severe symptomatic hyponatremia in a patient with schizoaffective disorder: a case study and literature review

IntroductionThe syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a serious condition associated with persistently high ADH with water retention despite sufficient vascular volume. Sodium valproate (VPA), an antiepileptic indicated to treat bipolar disorder, blocks sodium (Na) and calcium ions. Few studies have examined the association between VPA and SIADH.ObjectivesThis abstract has two interrelated objectives: (1) to describe a VPA-associated SIADH case study we encountered in our clinical setting; and (2) to review literature for other VPA-associated SIADH cases to illuminate associations and possible risk factors.MethodsAfter recording a case from clinical experiences, we completed a literature review of other cases of hyponatremia associated with VPA.We reviewed resulting artticles from searches in PubMed and in the aggregate Dartmouth Biomedical Library indices with no date or language parameters. We then searched those articles’ bibliographies.ResultsMs. A is a 63-year-old woman with schizoaffective disorder, bipolar type, hospitalized for the resurgence of visual hallucinations (VH) of “monsters” asking her to hurt herself and others. She had been adherent to VPA (500mg twice daily) and non-adherent to prescribed Olanzapine (25mg). On Day 1 (D1), her labs were concerning for serum Na 119mEq/L (n=135-145), serum osmolality (SOsm) 264mEq/L (n=275-295), and inappropriately high urine osmolality 111mOsm/kg (n &lt;100 mosmol/kg in hyponatremia) and urine Na 34mEq/L (n &lt;20 mosmol/kg in hypovolemic hyponatremia). Her VPA level was 73.6 mcg/mL.She was restarted on her home psychiatric medications for VH, and her hyponatremia responded to water restriction, with serum osmolality at 292mEq/L by D4 (see Figure). She was admitted to the inpatient psychiatric unit for concerns of persistent VH. On D13, her SOsm worsened to 267mEq/L and VPA was discontinued at that time. On D19, SOsm improved to 283mEq/L. Her VH responded well to discontinuing VPA and adding Risperidone (titrated to 6mg) and on D22 she was discharged home. Given the chronological sequence of her newly developed VH, the patient’s hallucinations were likely multifactorial, with contribution from hyponatremic encephalopathy-related psychosis.Our literature review found ten articles reporting thirteen other cases of VPA-associated SIADH (see Table). Our patient shared demographics with most previously reported cases: being older in age and having polytherapy and a low baseline Na. None of the previous case reports showed specific drug interactions to be particularly likely causes of hyponatremia.Image:Image 2:ConclusionsAlthough VPA-associated SIADH is a rare phenomenon, caution is warranted when evaluating patients with VPA use presenting acutely with psychosis and hyponatremia. These symptoms could be the manifestation of hyponatremic encephalopathy-related psychosis.Disclosure of InterestNone Declared

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.

Valproate-Associated Hyperammonemic Encephalopathy: Clinical Correlates and Management Strategies in a Tertiary Care Center.

Common adverse effects of valproate include sedation, tremor, gastrointestinal effects, and weight gain. Valproate-associated hyperammonemic encephalopathy (VHE) is an uncommon adverse effect of valproate therapy, which includes symptoms such as tremors, ataxia, seizures, confusion, sedation and coma. We report clinical features and management of 10 cases of VHE in a tertiary care center. In a retrospective chart review of case records from January 2018 to June 2021, 10 patients with VHE were identified and included in this case series. The data collected include demographic information, psychiatric diagnosis, comorbidities, liver function tests, serum ammonia and serum valproate levels, dosages and duration of valproate, management of hyperammonemia including dosage variations, discontinuation, adjuvant drugs used, and whether rechallenge was done. The most common indication of starting valproate was bipolar disorder (n = 5). All the patients had more than one physical comorbidity and risk factors for developing hyperammonemia. Seven patients received valproate at a dose higher than 20 mg/kg. The duration of valproate use varied from 1 week to 19 years before developing VHE. Dose reduction or discontinuation and lactulose were the most common management strategies used. All 10 patients improved. Among the 7 patients in whom valproate was discontinued, for 2 patients valproate was reinitiated in inpatient care with careful monitoring and was found to be well tolerated. This case series highlights the need for a high index of suspicion for VHE as it is frequently associated with a delayed diagnosis and recovery in psychiatric settings. Screening for risk factors and serial monitoring may allow earlier diagnosis and management.

The Awareness and Adherence of the Valproate Pregnancy Prevention Program: A Questionnaire Survey among Healthcare Professionals, Pharmacists, and Patients in Denmark.

The European Medicine Agency (EMA) provided additional recommendations regarding the use of valproate during pregnancy in 2018 by introducing a pregnancy prevention program (PPP). This study aimed to investigate the adherence and the impact of the PPP and the awareness of valproate teratogenicity among Danish healthcare professionals (HCPs) and patients. As part of the EMA initiated multi-country survey, web-based questionnaires were distributed among Danish general practitioners (GPs), medical specialists, pharmacists, and patients. A total of 90 prescribers, 98 pharmacists, and 103 patients were included in the study. Some 95.0% of the prescribers, 78.6% of the pharmacists, and 81.6% of the patients were aware of the teratogenic risks of valproate. The patient guide (27.8%), the HCP guide (23.3%), direct healthcare professional communication (23.3%), and the warning sign on the outer medication package (23.5%) were the most applied measures from the PPP. A total of 54.4% of the prescribers and 32.7% of the pharmacists informed patients about the importance of effective contraception during the use of valproate. The study showed that in Denmark HCPs and patients are highly aware of the teratogenic effects of valproate. However, adherence to and the impact of the measures included in the PPP were low.

Trends in antiseizure medications utilization among women of childbearing age with epilepsy in Poland between 2015 and 2019

PurposeTo determine trends in the use of antiseizure medications (ASMs) among women of childbearing age (WOCA) and girls aged 12–14 years with epilepsy between 2015 and 2019 in Poland. MethodsThe study used data from the Pex database, which captures information on prescriptions dispensed from 85% of community pharmacies in Poland. The prescriptions issued by neurologists who provide epilepsy care in Poland were studied. Six of the most commonly prescribed ASMs were analyzed: carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, topiramate, and valproate. ResultsThe use of valproate and carbamazepine decreased in all age groups. Among the newer ASMs, the use of lamotrigine, levetiracetam, and topiramate increased and oxcarbazepine decreased significantly in WOCA. The only subgroup with statistically significant changes in all ASMs prescriptions were women aged 19–34 years. For girls aged 12–14 years, significant changes were found only for valproate and carbamazepine. In the last year of observation (2019) valproate and lamotrigine accounted for two-thirds of ASMs units prescribed to WOCA. Valproate accounted for half of the prescribed drug units in girls aged 12–14 years. The lowest rates of VPA prescriptions were found in women aged 19–34 years. ConclusionsThere is a change in prescribing habits in WOCA with epilepsy in Poland with trends toward using less teratogenic ASMs. However, many WOCAs are treated with valproate and topiramate despite their known teratogenicity risk. Valproate is still the most commonly prescribed ASM in WOCA and girls aged 12–14 years. Educational interventions for healthcare professionals are needed to improve prescribing practices in WOCA with epilepsy in Poland.

The effect of nuclear factor 1B polymorphisms and valproate use on clozapine metabolism

The effect of nuclear factor 1B polymorphisms and valproate use on clozapine metabolism

Comparison of myocardial perfusion between the users of two antiepileptic medications: valproate vs. carbamazepine.

The prevalence of coronary artery disease (CAD) is high in patients with epilepsy using antiepileptic drugs (AED). Epilepsy, AED, or the type and duration of AED use , may contribute to higher CAD risk.In this study, myocardial perfusion imaging (MPI) was compared between patients using carbamazepine and valproate. Out of 73 patients receiving carbamazepine or valproate monotherapy for more than 2 years, visited at a tertiary referral clinic, 32 patients participated in a 2-day stress and rest phases MPI. For each phase, 15-25 mCi 99mTc-MIBI was injected, at peak exercise or by pharmacologic stimulation for the stress phase. SPECT with cardiac gating was done by a dual-head gamma camera and processed and quantified. Scans with at least one definite reversible hypo-perfusion segment were considered abnormal. Seventeen patients received carbamazepine monotherapy and 15 valproates. Age and duration of AED use were similar between the groups. Two scans were abnormal (6.3%) both in valproate group (13.3%). Duration of AED use was higher in patients with abnormal scans. In patients receiving monotherapy >2 years, the frequency of abnormal MPI was similar between groups (P-value=0.12). In patients receiving monotherapy > 5 years, prevalence of abnormal MPI was higher in the valproate group (28.6% vs. 0.0%; P-value=0.042). Considering valproate subgroup, ischemic patients had higher duration of AED use, comparing with the normal patients (17.0±4.2 vs. 6.4±4.8, P-value=0.014). MPIs were abnormal in patients receiving valproate after 5 years compared to patients receiving carbamazepine. Long-term valproate use may increase the risk of CAD.

A case of acute poisoning with thiamethoxam

Thiamethoxam belongs to the second generation of neonicotinoid insecticides, and case of acute poisoning with thiamethoxam had never reported in China. This paper reviewed a case of oral poisoning with thiamethoxam pesticides, the patient suffered vomiting, generalized convulsions, confusion, and decreased oxygen saturation. After treated with gastric lavage, ventilator support, and the use of propofol, midazolam, sodium phenobarbital, and sodium valproate, the convulsions could not be controlled. Untill treated with penehyclidine hydrochloride and hemoperfusion combined with hemofiltration, the patient finally recovered and was discharged from the hospital. We suggest that the main treatments for acute severe thiamethoxam poisoning are decontamination and symptomatic support, pentoxifylline hydrochloride and hemoperfusion combined with hemofiltration may improve the patients' prognosis.

Women of childbearing age: What antiseizure medications are they taking?

Women of childbearing age: What antiseizure medications are they taking?

Avis d’experts français sur la prise en charge des femmes en âge de procréer et enceintes souffrant d’un trouble bipolaire traitées par valproate

IntroductionThe perinatal period is associated with high risk of relapses in women with untreated bipolar disorder (BD) and can have significant consequences on foetal and child development. Valproate is an effective mood stabilizer in BD but it is also the anticonvulsant associated to the highest risks of neurodevelopmental disorders and congenital malformations. The National Agency for the Safety of Medicines and Health Products (ANSM) changed the conditions of use and prescription of valproate in France in 2015. Its prescription is now contraindicated (i.e., not to be prescribed) in women able to have children unless alternative treatments are ineffective or not tolerated. Moreover, valproate could only be prescribed if the protocol of a specific pregnancy prevention program is followed. MethodsA panel of experts from the French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) provided consensus-based recommendations for switching and discontinuation of valproate in women with BD. The development of these recommendations consisted of an adaptation to French clinical practice based on a European expert opinion published in 2019. The experts discussed five real-world clinical situations in light of the scientific evidence and their clinical experience (a. Stable BD patient with valproate monotherapy who is planning pregnancy, b. Stable BD patient with valproate polytherapy who is planning pregnancy, c. Unstable BD patient with frequent relapses and valproate polytherapy who is planning pregnancy, d. Stable BD patient treated with valproate and unexpected pregnancy, e. Unstable BD patient treated with valproate and unexpected pregnancy) and developed, through several rounds of exchange drafts, a French version of clinical recommendations. ResultsFirst of all, some factors need to be considered for establishing personalized practical recommendations for a safe and effective switching or discontinuation of valproate in any clinical situations: planned pregnancy or unplanned pregnancy or current pregnancy, the existence or not of a pregnancy risk minimization program and a complete treatment history. Other factors that should be considered are the predominant polarity, the severity, the stability, the comorbidities associated with BD, the beliefs toward treatments, the family situation and the preference of the patient. The modalities for switching or discontinuation of valproate in women with BD were related to the clinical situation. First-line therapeutic alternatives such as lithium, lamotrigine, quetiapine, olanzapine or aripiprazole were preferred for patients suffering from a clinically stable BD considering pregnancy or pregnant. In patients suffering from clinically unstable BD, to reach stability was considered first. A shared decision-making should be systematically implemented and the patient must be fully informed of the risks related to an in-utero exposure to valproate, and the risks of the discontinuation/switch that is considered. ConclusionAlthough the adaptation to French practice of the recommendations from the European expert opinion highlighted some differences in the criteria taken into consideration to guide the therapeutic decision, this expert advice will guide the clinician for switching and discontinuation of valproate in BD women able to have children or pregnant.

Measures to Mitigate Sodium Valproate Use in Pregnant Women With Epilepsy.

Sodium valproate is a sodium saltof valproic acid. It is often used in the medical treatment of several conditions like epilepsy, bipolar disorder, mania, and migraines. This review debates whether the usage of valproic acid is appropriate in pregnancy. It also lists the various neonatal deformities and other teratogenic effects the said drug presents due to prenatal exposure to the drug and the implications of continuing drug therapy in certain situations. We should often weigh the outcomes and implement it only in conditions where its use is inevitable. It also includes the importance of awareness among middle-aged women with mental illness regarding the teratogenic effects of sodium valproate use and the relevance of discussion by physicians with patients regarding the usage of this drug despite being aware of the complications. It also explores other treatment options and modalities that can be used in the place of valproic acid for epilepsy and bipolar disorder in pregnant women and women of the reproductive age group, and how we can mitigate the usage of this drug by implementing various measures by referring to various guidelines present in different areas of the world. In summary, this article explores the numerous teratogenic effects sodium valproate presents in pregnancy, alternative medications, and treatment options instead of valproate. It also enumerates conditions where valproate use is necessary and how we can reduce and prevent the usage of valproate in pregnancy by opting for pregnancy prevention programs during valproate use and various other guidelines.

Changes in the first anti-seizure medication prescribed for children and adolescents with epilepsy in a tertiary clinical center in Serbia over two decades.

We assessed the prevalence of the use of new anti-seizure medications and valproate in the female population over two decades. We conducted a retrospective observational cross-sectional study of medical records of children and adolescents (4 - 19 years old) with newly diagnosed epilepsy in a tertiary clinical center in Serbia from 1997 to 1999 and 2017 to 2019. The statistical analysis revealed significant changes in the treatment of generalized and focal seizures and all etiologies of epilepsy. Valproate use in the adolescent girl population decreased significantly from 2017 to 2019. The prescription pattern of the initial anti-seizure medication changed significantly over the two decades. The results correspond to current guidelines and recommendations.