Efficacy, Safety, and Retention Rate of Extended-Release Divalproex Versus Conventional Delayed-Release Divalproex: A Meta-Analysis of Controlled Clinical Trials.

Purpose: A novel once-daily divalproex-extended release (ER) dose formulation has been developed; this formulation prolongs the therapeutic serum levels of the drug, compared with the twice-daily conventional divalproex-delayed release (DR) formulation. This study aimed to systematically examine and compare the efficacy, safety, and retention rates of the ER divalproex (VPA-ER) and conventional DR divalproex (VPA-DR) formulations. Methods: Randomized control trials (RCTs) reporting the efficacy, adverse events (AEs), and medication compliance of ER and DR divalproex were searched in online databases, including PubMed, Embase, and Cochrane Library databases, by searching MeSH words and term words. Observational studies with potential biases were excluded. The meta-analysis was performed using Stata 16.0 software. Findings: Thirteen RCTs, involving 1,028 participants, were included in this meta-analysis. Efficacy, AEs, and drug retention rates were the main study outcomes. According to our study, VPA-ER presented clinically significant benefits compared with the placebo in the population with bipolar disorder (BD) (39.5% versus 27.2%, p < 0.001). A similar efficacy of VPA-ER and VPA-DR in controlling seizures was observed in epilepsy patients (87.4% versus 86.5%, p = 0.769). A significantly lower incidence of AEs was reported in the VPA-ER group than in the placebo group (26.8% versus 34.8%, p = 0.003). By contrast, there was no evidence of difference in safety between VPA-ER and VPA-DR (29.4% versus 30.5%, p = 0.750). In addition, the drug retention rate was significantly lower in the VPA-ER group than in the placebo group (76.0% versus 82.7%, p = 0.020), especially in migraine patients (p = 0.022) and in patients who were treated for fewer than 4 weeks (p = 0.018). Implications: The efficacy of VPA-ER was significantly superior to that of the placebo treatment, which provided efficacy similar to that of conventional VPA-DR. VPA-ER is well tolerated with a low rate of AEs compared to the placebo. In addition, the acceptable medicine compliance of VPA-ER was conducive to the long-term maintenance treatment of chronic diseases. Although we analyzed open labels and crossover design RCTs, large-scale multicenter studies on the efficacy and medicine compliance of new ER formulations with less AEs are required to validate our conclusion.

Effect of different physical activity training methods on epilepsy: A protocol for systematic review and meta-analysis.

BACKGROUND: Over the past few decades, people with epilepsy were advised not to engage in sports based on the fear that sporting activity may cause injuries, potentially induce seizures, and have a negative effect on disease course. However, in recent years, numerous studies have indicated a positive role of physical exercise in reducing the frequency of seizures and improving health condition of patients with epilepsy. The purpose of this study was to compare the effects of different physical exercise programs on the symptomatology and health condition of individuals with epilepsy and provide guidance for selecting the optimal modality of physical exercise for patients with epilepsy via a meta-analysis of available literature. METHODS: A literature search was carried out in MEDLINE via PubMed, Cochrane Library, EBSCO, Embase, China National Knowledge (CNKI), and Wan fang databases to gather relevant data about different physical exercise modalities and epilepsy. We will use Endnote X9 software for studies selection and Stata16.0 software for the data analysis. RESULTS: This present study aimed to provide the most up to date evidence and recommendations for clinicians and epilepsy patients to choose an optimal type of exercise. CONCLUSION: Aerobic exercise and resistance exercises both had a positive effect on epilepsy patients. Persons with epilepsy should be encouraged to participate in sports activities.INPLASY registration number: INPLASY202220070.

Efficacy, safety, and retention rate of extended-release divalproex versus conventional delayed-release divalproex: A protocol for systematic review and meta-analysis.

BACKGROUND: A novel once-daily divalproex-extended release (VPA-ER) dose formulation has been developed, which prolongs therapeutic serum levels compared with that of twice-daily conventional divalproex-delayed release (VPA-DR). Currently, there is lack of meta-analysis focusing on drug retention rate between VPA-ER and VPA-DR. Thus, our study is the first one that aims to systematically examine and compare the efficacy, safety, and retention rate of VPA-ER and VPA-DR. METHODS: Online databases including MEDLINE via PubMed, Cochrane Library, Embase (up to October 30, 2021) will be applied for literature screen. We will conduct meta-analysis by using Stata16.0 software. RESULTS: This study aims to evaluate the efficacy, safety, and drug retention rate of VPA-ER versus conventional VPA-DR. CONCLUSION: Once-daily VPA-ER may present a positive efficacy and not increase the incidence of AEs and has a higher retention rate for patients, which can be used as a substitute for conventional VPA-DR.INPLASY registration number: INPLASY2021110090(DOI: 10.37766/inplasy2021.11.0090).

Magnesium valproate adjuvant therapy on patients with dementia: A protocol for systematic review and meta-analysis.

BACKGROUND: With the aging population, the prevalence and incidence of dementia disease will continue to rise, and the associated economic burden is increasing as well. However, the available anti-dementia therapeutic arsenal is limited. Meanwhile, magnesium valproate (VPM) as an adjuvant therapy had a general positive effect on the cognitive function and psychiatric symptoms of patient with dementia (PwD). At present, there is lack of meta-analysis focusing on cognitive improvement and disease-modifying about VPM-assisted therapy in the present peer-reviewed literature. Thus, we aimed to likely analyze the efficacy and safety of VPM adjuvant therapy of PwD. METHODS: We will research MEDLINE via PubMed, Cochrane Library, EBSCO, Embase, China National Knowledge (CNKI) and Wan fang databases to gather relevant data on VPM assistant therapy on the PwD. Meta-analysis will be performed using Stata16.0 software. RESULTS: We aim to evaluate the efficacy and safety of VPM in the adjuvant treatment of PwD. CONCLUSION: VPM maybe plays an active role in the treatment of dementia patients and this research will provide reliable evidence for clinicians in therapy of PwD. INPLASY REGISTRATION NUMBER: INPLASY2021110038 (DOI: 10.37766/inplasy2021.11.0038).

Risk of Valproic Acid-Related Tremor: A Systematic Review and Meta-Analysis.

Purpose: To evaluate the incidence and risk of tremor in patients treated with valproic aid (VPA) monotherapy. Methods: We searched the PubMed, Embase, and Cochrane Library databases to gather relevant data on tremor in patients taking VPA and other drugs and performed a meta-analysis using Stata15.1 software. Results: Twenty-nine randomized controlled trials (RCTs) met the inclusion criteria and were included in the meta-analysis. The overall incidence of tremor in patients receiving VPA therapy was 14% [OR = 0.14, 95% CI (0.10-0.17)]. The pooled estimate risk of tremor showed a significant difference between patients treated with VPA and all other drugs [OR = 5.40, 95% CI (3.22-9.08)], other antiepileptic drugs (AEDs) [OR = 5.78, 95% CI (3.18-10.50)], and other non-AEDs [OR = 4.77, 95% CI (1.55-14.72)]. Both a dose of <1,500 mg/d of VPA [included 500 mg/d: OR = 3.57, 95% CI (1.24-10.26), 500-999 mg/d: OR = 3.99, 95% CI (1.95-8.20), 1,000-1,499 mg/d: OR = 8.82, 95% CI (3.25-23.94)] and a VPA treatment duration of <12 m [included ≤ 3 months: OR = 3.06, 95% CI (1.16-8.09), 3-6 months: OR = 16.98, 95% CI (9.14-31.57), and 6-12 months: OR = 4.15, 95% CI (2.74-6.29)] led to a higher risk of tremor than did other drugs, as did higher doses and longer treatment times. Conclusion: Compared with other drugs, VPA led to a higher risk of tremor, and the level of risk was associated with the dose and duration of treatment.