Valproic acid can reduce the frequency of seizures through various mechanisms and is widely used in clinical practice as a monotherapy or adjunctive treatment for various types of epilepsy and epileptic syndromes. In addition, valproic acid has significant therapeutic effects on comorbidities associated with epilepsy, such as migraines and psychiatric disorders. It can also be effective in terminating status epilepticus and is commonly used as a broad-spectrum antieseizure medication in clinical settings. However, valproic acid has side effects such as teratogenicity, infertility, and menstrual disorders. Additionally, when used in combination with other drugs, the interactions between medications should be carefully considered. Therefore, in clinical practice, it is necessary to strictly adhere to the indications and dosage regimens for the use of valproic acid. This article provides a comprehensive review of the use of valproic acid in different types of seizures, epileptic syndromes, comorbidities associated with epilepsy, post-craniotomy cases, status epilepticus, and special populations. It also summarizes the combination therapy of valproic acid with other drugs, providing a basis for the rational use of valproic acid and individualized drug treatment selection for epilepsy patients.
Objective To study the correlation of changes in liver function during long-term treatment with sodium valproate (VPA) in children with epilepsy in Putian, and to explore individualized administration to improve the compliance of children with medication. Methods The blood concentration of VPA and related biochemical test data of 350 children with epilepsy from June 1, 2018 to March 1, 2021 were collected in our hospital. According to the results of VPA blood concentration, they were classified as low Blood concentration group (<50 μg/mL), therapeutic blood concentration group (50 ~ 100 μg/mL) and high blood concentration group (>100 μg/mL). Results There was no significant difference in liver function indexes between the VPA treatment group and the control group (P>0.05). There were significant differences in liver function ALT, AST, AST/ALT, TBIL and DBIL among the groups of VPA blood concentration range (P<0.05). The abnormal incidence of liver function indexes of high blood drug concentration was lower in the concentration group and higher in the treatment concentration group, and there were differences (P<0.05). Conclusion Abnormal liver function in the high blood drug concentration treatment groupis quite common, and the dose of the drug should be adjusted in time to avoid liver damage caused by the VPA.
Objective The study was performed to compare the efficacy and effect on quality of life of sodium valproate (VPA) sustained-release tablets versus topiramate (TPM) in newly diagnosed adult symptomatic epilepsy. Methods This is aprospective, randomized controlled trial on 200 patients newly diagnosed as adult symptomatic epilepsy in Sichuan Province People’s Hospital druing September 2014 to December 2016. The patients were randomly divided into VPA group (n=110) and TPM group (n=90). Then we evaluated the efficacy, retention rate, adverse reactions, and quality of life of the two groups after one year of treatment. Results The total effective rate of VPA group was 69.1%, and the rate of no seizures was 38.2%; the total effective rate of TPM was 62.2%, and the rate of no seizures was 42.2%. No statistically significant difference in the effective rate and no seizure rate was found between the two groups. There was no statistical difference in the retention rate between the two groups(69.1% vs. 65.6%, P>0.05) . The incidence of adverse reactions of VPA was significantly lower than that of TPM (9.1%vs. 20%, P<0.05). The quality of life of the two groups was significantly improved from baseline before treatment. VPA group showed significantly better performance than TPM group on mood and cognitive improvement (P<0.05). Conclusion ① There was no significant difference in efficacy and retention rate between VPA sustained-release tablet and TPM on adult patients with symptomatic epilepsy after one year's treatment; ② The incidence of adverse reactions of TPM group was significantly higher than that of VPA group; ③ VPA sustained-release tablets and TPM can significantly improve the overall quality of life of patients, and VPA sustained-release tablets is significantly better than topiramate on the improvement of emotional and cognitive function.
ObjectiveTo compare the curative effect of levetiracetam combined with lamotrigine and sodium valproate on postoperative patients with temporal lobe epilepsy. MethodsA total of 186 postoperative patients with temporal lobe epilepsy during August 2012 to August 2014 in our hospital were divided into levetiracetam combined with lamotrigine group (n=98), and sodium valproate group (n=88) based on postoperative different antiepileptic drugs treatment. Antiepileptic treatment were followed up for 12~48 months.Curative effect and adverse reaction were observed. Reservation rates and incidence rates of adverse reaction were calculated in the two groups. ResultsIn levetiracetam combined with lamotrigine group, EngelⅠratio was 72.4%(71), EngelⅡratio was 17.3%(17), EngelⅢratio was 7.1%(7), and EngelⅣratio was 3.2%(3);in sodium valproate group, EngelⅠratio was 67.0%(59), EngelⅡratio was 21.6%(19), EngelⅢratio was 9.1%(8), and EngelⅣratio was 2.3%(2), and the difference was not statistically significant in the same grade of two groups (P > 0.05).Reservation rate and incidence rate of adverse reaction in levetiracetam combined with lamotrigine group were 90.8%(89) and 15.3%(15) respectively.While those in sodium valproate group were 80.7%(71) and 36.4%(32) respectively.The differences were statistically significant between the two groups (P < 0.05). ConclusionsLevetiracetam combined with lamotrigine treatment on postoperative patients with temporal lobe epilepsy may have better curative effects than sodium valproate treatment, and levetiracetam combined with lamotrigine has its advantage in reservation rate and less adverse reaction.
ObjectiveTo explore the inhibition action of valproic acid to inflammatory cells and smooth muscle cells then to find out that valproic acid (VPA) can repress rat thoracic aortic aneurysm or not. MethodsThe model of rat thoracic aortic aneurysm was built through the method of soaking the adventitia of artery using porcine pancreatic elastase (PPE). The rats were divided into three groups:a normal saline blank control group (a C group), an adventitia soaked PPE group (a P group), and adventitia soaked PPE plus intraperitoneal injection by injecting intraperitioneal VPA 200 mg/kg for seven days (a PV group).The animals of the three groups were all using vascular ultrasound to detect blood vessel diameter. Animals were killed after operation to observe the general morphology of vascular aneuysm and do the immunohistochemial, morphological, protein analysis of interleukin 1 (IL-1), interleukin 6 (IL-6), smooth muscle 22 alpha (SM22α), matrix metallopeptidase 2 (MMP-2), MMP-9 and Western blot by drawing animals on the 14th day. ResultsThe vessels diameter in the PV group was narrower than that in the P group (P value<0.05). HE staining, immunohistochemistry and Western blot displayed that the cells in the P group were in disorder arrangement and interstitial disorder while the cells in the PV group maintained better albumin layer. The protein expressions of IL-1, IL-6, MMP-2, and MMP-9 in the PV group decreased except that SM22α increased. ConclusionVPA can inhibit phenothpic transforming of aneurysm inflammatory cells and smooth muscle cells, reduce the levels of cell proliferation, decrease the secretion of matrix metalloproteinases, and depress tumor growth of rat thoracic aorta.
ObjectiveTo investigate the effect of valproic acid (VPA) coadministred with lamotrigine (LTG) on epileptic patients' ammonia and evaluate the influencing factors of elevated blood ammonia in epileptic patients.MethodsA retrospective analysis of clinical data from 146 patients with epilepsy (including newly diagnosed epilepsy patients) who were admitted to the Seventh Affiliated Hospital of Sun Yat-Sen University from May 2018 to April 2020 was performed. The patients were divided into no antiepileptic drug group (group A), VPA group only (group B) and VPA combined LTG group (group C), and the concentration of the blood ammonia of the patients were analyzed.ResultThe average ammonia levels in groups A, B and C were (18.14±1.19), (25.89±0.87) and (36.60±4.34) μmol/L, and the incidence of blood ammonia higher than normal were 2.77%, 8.89% and 20.0%, respectively.The difference between group B and group A and group C were statistically significant (P<0.05), the difference between group C and group A was statistically significant (P<0.05).ConclusionPatients with epilepsy who use VPA were at increased risk of blood ammonia and LTG can increase ammonia in epileptic patients who were treated with VPA. So when VPA was combined with LTG, more attention should be paid to ammonia of patient to avoid adverse reactions.
ObjectiveTo explore the protective effects of sodium valproic acid (VPA) on oxidative stress injury of osteoblasts induced by carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and its mechanism. Methods Osteoblasts were isolated from the skulls of 10 newborn Sprague Dawley rats and cultured by tissue block method, and the 1st generation cells were identified by alkaline phosphatase (ALP) and alizarin red staining. The 3rd generation osteoblasts were cultured with 2-18 μmol/L CCCP for 2-18 minutes, and cell counting kit 8 (CCK-8) was used to detect the cell survival rate. An appropriate inhibitory concentration and culture time were selected for the preparation of osteoblasts oxidative stress injury model based on half maximal concentration principle. The cells were cultured with 0.2- 2.0 mmol/mL VPA for 12-72 hours, and CCK-8 was used to detect cell activity, and appropriate concentration was selected for further treatment. The 3rd generation cells were randomly divided into 4 groups, including blank control group (normal cultured cells), CCCP group (the cells were cultured according to the selected appropriate CCCP concentration and culture time), VPA+CCCP group (the cells were pretreated according to the appropriate VAP concentration and culture time, and then cultured with CCCP), VPA+CCCP+ML385 group (the cells were pretreated with 10 μmol/L Nrf inhibitor ML385 for 2 hours before VPA treatment, and other treatments were the same as VPA+CCCP group). After the above treatment was complete, the cells of 4 groups were taken to detect oxidative stress indicators [reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA)], cell apoptosis rate, ALP/alizarin red staining, and the relative expressions of osteogenic related proteins [bone morphogenetic protein 2 (BMP-2), RUNX2], anti-apoptotic family protein (Bcl2), apoptotic core protein (Cleaved-Caspase-3, Bax), channel protein (Nrf2) by Western blot. Results The osteoblasts were successfully extracted. According to the results of CCK-8 assay, the oxidative stress injury model was established by 10 μmol/L CCCP cultured for 10 minutes and 0.8 mmol/mL VPA cultured for 24 hours was selected for subsequent experiments. Compared with blank control group, the activity and mineralization capacity of osteoblasts in CCCP group decreased, the contents of ROS and MDA increased, the activity of SOD decreased, and the apoptosis rate increased. Meanwhile, the relative expressions of BMP-2, RUNX2, and Bcl2 decreased, and the relative expressions of Cleaved-Caspase-3, Nrf2, and Bax increased. The differences were significant (P<0.05). After further VPA treatment, the oxidative stress damage of osteoblasts in VPA+CCCP group was relieved, and the above indexes showed a recovery trend (P<0.05). In VPA+CCCP+ML385 group, the above indexes showed an opposite trend (P<0.05), and the protective effects of VPA were reversed. Conclusion VPA can inhibit the CCCP-induced oxidative stress injury of osteoblasts and promote osteogenesis via Keap1/Nrf2/Are pathway.