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1.
Effects of Sodium Valproate Monotherapy on Blood Liver Enzyme Levels in Patients with Epilepsy: A Meta-Analysis.
Fu, J, Tao, T, Li, Z, Chen, Y, Chen, X, Li, J, Peng, L
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2021;(7):425-434
Abstract
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.
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2.
Intravenous sodium valproate in status epilepticus: review and Meta-analysis.
Liampas, I, Siokas, V, Brotis, A, Zintzaras, E, Stefanidis, I, Dardiotis, E
The International journal of neuroscience. 2021;(1):70-84
Abstract
Objective: Status epilepticus (SE) is a common neurologic emergency. The present study constitutes a meta-analysis of published randomized control trials (RCTs) evaluating the use of intravenous sodium valproate (VPA) in SE.Methods: MEDLINE and Cochrane databases were comprehensively searched, while retrieved RCTs and meta-analyses were manually screened. Prespecified outcome measures included seizure-cessation, 24 h-efficacy, constitute (liver enzyme increase, arrhythmias, bone-marrow suppression, hypotension and respiratory depression) and severe (life-threatening) adverse events (AEs). Evidence synthesis was performed when appropriate, using Random-Effects (RE) or Fixed-Effects (FE) model based on heterogeneity between trials (homogeneity assumed when PQ > 0.1 and I2 < 50%). Outcomes were assessed using Odds-Ratios (ORs) and 95%Confidence-Intervals (95% CIs). Every available comparison was investigated in terms of efficacy and tolerability.Results:Thirteen studies were retrieved and five comparisons were available, four of which involved two or more studies. Results were compatible with no significant difference between VPA and Phenytoin both in terms of efficacy and tolerability [seizure-cessation: FE-OR = 1.99, 95% CI = (0.83-4.75), 24 h-efficacy: FE-OR = 1.32, 95% CI = (0.60-2.89), composite AEs: FE-OR = 0.45, 95% CI = (0.17-1.21)]. Phenobarbital proved more commonly associated with composite AEs than VPA [seizure-cessation: RE-OR = 0.68, 95% CI = (0.05-9.44), 24 h-efficacy: RE-OR = 0.88, 95% CI = (0.02-33.9), composite AEs: FE-OR = 0.26, 95% CI = (0.09-0.82), severe AEs: FE-OR = 0.30, 95% CI = (0.04-2.28)]. Diazepam was determined inferior to VPA concerning safety issues [seizure-termination: FE-OR = 0.77, 95% CI = (0.34-1.79), severe respiratory depression: FE-OR = 0.06, 95% CI = (0.01-0.48), severe hypotension: FE-OR = 0.09, 95% CI = (0.01-0.72)]. The combination of Lorazepam (LZP) with VPA and the combination of LZP with Levetiracetam presented no difference in efficacy [24h-efficacy: FE-OR = 0.68, 95% CI = (0.37-1.24)].Conclusions: Although, additional high-quality RCTs are warranted, according to our results, VPA can be considered a safe and effective option in the management of SE.
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3.
Intravenous sodium valproate for acute migraine in the emergency department: A meta-analysis.
Wang, F, Zhang, H, Wang, L, Cao, Y, He, Q
Acta neurologica Scandinavica. 2020;(6):521-530
Abstract
The role of intravenous sodium valproate (iVPA) in acute migraine attack has not been completely established. The aim of this updated review was to evaluate the efficacy and safety of iVPA in patients with acute migraine in the emergency department. We searched the PubMed, Web of Science, and Cochrane Library databases for relevant randomized controlled trials (RCTs). The primary outcome was improvement of headache intensity and headache relief. The need for rescue therapy, recurrence of headache, and number of adverse events was also assessed. Seven double-blinded RCTs involving 682 patients were analyzed. Overall, patients receiving iVPA had less improvement of headache intensity (SMD: -0.39, 95% CI: -0.73 to -0.06, P = .02) and lower rate of headache relief (OR: 0.51, 95% CI: 0.33 to 0.77, P = .002) than those receiving other active comparators. In addition, iVPA increased the odds of rescue therapy compared with other active drugs (OR: 3.76; 95% CI: 1.96 to 7.20, P < .0001). Subgroup analysis showed that iVPA was comparable to dexamethasone, with similar improvement of headache intensity, and recurrence of headache. For migraine without aura, we found no significant difference in headache intensity improvement when iVPA was compared with active comparators (SMD: -0.00, 95% CI: -0.54 to 0.54, P = 1.00). iVPA was inferior to the studied comparators and was comparable to dexamethasone for aborting migraine attack. Based on the available evidence, iVPA may be a reasonable alternative or salvage therapy. In particular, iVPA might be a promising agent for migraine with aura and migraine status.
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4.
Valproate decreases vitamin D levels in pediatric patients with epilepsy.
Xu, Z, Jing, X, Li, G, Sun, J, Guo, H, Hu, Y, Sun, F, Wen, X, Chen, F, Wang, T, et al
Seizure. 2019;:60-65
Abstract
PURPOSE To compare Vitamin D (Vit D) levels in children with epilepsy on valproate monotherapy with healthy controls. METHODS A meta-analysis performed on articles identified from PubMed and Web of Science online databases evaluated using National Institute of Health National Heart, Lung, and Blood Institute Study Quality Assessment Tools. Subgroup analyses and publication bias assessments were also performed. RESULTS Eleven publications were eligible based on inclusion/exclusion criteria for the meta-analysis. Results noted a decrease in the mean Vit D level in children with epilepsy on valproate monotherapy compared with healthy children with a Standard Mean Difference = -0.313 [-0.457, -0.169]. Cumulative meta-analysis showed progressive negative effect of valproate therapy on Vit D levels across time. Other antiepileptic medications caused a similar effect on Vit D status. There was no evidence of publication bias in the analyses. Type of study design and country of origin introduced heterogeneities into the meta-analyses. CONCLUSION This meta-analysis provides evidence that long-term therapy with valproate causes a decrease in Vit D levels in children. Therefore, in children with a seizure disorder on long-term valproate therapy, 25-OH-Vit D levels should be monitored and appropriate supplementation implemented if levels are deficient.
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5.
CPS1 T1405N polymorphism, HDL cholesterol, homocysteine and renal function are risk factors of VPA induced hyperammonemia among epilepsy patients.
Chen, L, Tian, Q, Zhang, M, Chen, D, Gao, X, Yang, H, Li, H, Li, C, Wen, J, Li, Y, et al
Epilepsy research. 2019;:139-143
Abstract
PURPOSE Valproic acid (VPA) is frequently used in the treatment of epilepsy. The adverse effects of VPA include hyperammonemia (HA) which is characterized by abnormally elevated blood ammonia level. Carbamoyl-Phosphate Synthase 1 (CPS1) is an enzyme catalyzing the initial step of removing ammonia from blood. Studies have demonstrated that the CPS1 polymorphism rs1047891-A allele carriers were susceptible to VPA-induced HA. However, the evidences remained controversial. In this study, we sought to validate the association between rs1047891 and VPA-induced HA by combining the association results from previous studies together. METHODS We first conducted a systematic meta-analysis to determine whether rs1047891 was statistically significant. Then, we further evaluated the pleiotropic effects of rs1047891 using published genome-wide association studies (GWAS) and UKBB results. A conditional analysis was conducted to investigate whether the association between rs1047891 and VPA-induced HA was mediated by cardiovascular or renal disease risk factors or vice versa. RESULTS The allelic, dominant and recessive ORs of rs1047891-A were all significant in our fixed-effect meta-analysis. In GWAS catalog and UKBB data, rs1047891 was associated with basal metabolic rate, adiposity and hematology traits, cardiovascular and renal disease risk factors. We further proved that plasma HDL cholesterol and homocysteine level, in addition to eGFR by serum creatinine, were associated with VPA-induced HA risk independently from rs1047891 polymorphism. CONCLUSION In conclusion, the SNP rs1047891 was associated with VPA-induce HA among epilepsy patients. Meanwhile, plasma HDL cholesterol and homocysteine level had independent effects from it.
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6.
Effects of Second-Generation Antiepileptic Drugs Compared to First-Generation Antiepileptic Drugs on Bone Metabolism in Patients with Epilepsy: A Meta-Analysis.
Fu, J, Peng, L, Li, J, Tao, T, Chen, Y
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2019;(8):511-521
Abstract
We conducted this meta-analysis to evaluate effects of second-generation anti-epileptic drugs (AEDs; levetiracetam, lamotrigine) compared to first-generation AEDs (valproic acid, carbamazepine) on bone metabolism in epilepsy patients. PubMed, Web of Science, Clinical trials.gov, Wanfang, and China national knowledge infrastructure databases were searched. Ten trials were included. Results showed: (1) The overall SMD for changes of serum calcium, phosphorus, ALP, and PTH levels from baseline of LEV versus first-generation AEDs were 1.00 (95% CI=0.23-1.77, Z=2.56, p=0.01), 0.98 (95% CI=- 0.05 to 2.01, Z=1.86, p=0.06), - 1.17 (95% CI=- 2.08 to - 0.25, Z=2.50, p=0.01), 0.07 (95% CI=- 0.14 to 0.27, Z=0.63, p=0.53), respectively. (2) The overall SMD for changes of serum calcium, phosphorus, ALP, and PTH levels from baseline of LTG versus first-generation AEDs were -0.16 (95% CI=- 0.47 to 0.16, Z=0.99, p=0.32), -0.05 (95% CI=- 0.55 to 0.44, Z=0.22, p=0.83), 0.10 (95% CI=- 0.53 to 0.73, Z=0.31, p=0.75), -0.05 (95% CI=- 0.52 to 0.42, Z=0.22, p=0.83), respectively. Overall, our results indicate that compared to first-generation AEDs, LEV has less adverse effects on blood bone metabolism markers in epilepsy patients, while LTG does not. However, due to small number of included studies, our results warrant additional research.
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7.
Effects of valproic acid on bone mineral density and bone metabolism: A meta-analysis.
Fan, D, Miao, J, Fan, X, Wang, Q, Sun, M
Seizure. 2019;:56-63
Abstract
PURPOSE Numerous studies have shown that the risk of fracture is increased by long-term antiepileptic drugs (AEDs). Valproic acid (VPA) is one of the most commonly used AEDs. In this meta-analysis, we aimed to assess the effects of VPA on bone mineral density (BMD) and bone metabolism. METHODS PubMed, Embase, Cochrane and Web of Science databases were searched from inception to January 2019 for articles focusing on the effects of VPA on BMD and bone metabolism in adults or children. A meta-analysis was performed using RevMan 5. 3 software. RESULTS 18 studies were included in the meta-analysis. The BMD of lumber spine (MD= -0.06, 95%CI: -0.09 to -0.03, P < 0.0001) and femoral neck (MD= -0.05, 95% CI= -0.08 to -0.01, P = 0.02) was markedly decreased in the VPA group compared to healthy controls. Serum bone-specific alkaline phosphatase (BALP) level (SMD = 0.85, 95% CI: 0.30-1.40, P = 0.002) was notably increased in the VPA group compared to healthy groups. In the child group, the serum parathyroid hormone (PTH) level was higher than in healthy groups (SMD= -0.22, 95% CI: -0.40 to -0.04, P = 0.02); besides, the serum 25-hydroxy vitamin D3 (25(OH)D3) level was decreased (SMD= -0.22, 95% CI: -0.40 to -0.04, P = 0.02), while no significant alteration of these parameters was noted in the adult VPA group (P ≥ 0.05). CONCLUSIONS VPA may reduce the BMD of lumbar spine and femoral neck in patients with epilepsy while increasing the serum BALP level. Serum PTH level are increased and serum 25(OH)D3 level decreased in children with epilepsy treated with VPA. These parameters were unaltered in adults.