PMID- 35479307
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Efficacy, Safety, and Retention Rate of Extended-Release Divalproex Versus 
      Conventional Delayed-Release Divalproex: A Meta-Analysis of Controlled Clinical 
      Trials.
PG  - 811017
LID - 10.3389/fphar.2022.811017 [doi]
LID - 811017
AB  - 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.
CI  - Copyright (c) 2022 Zhang, Li, Wan, Bai, Gan, Wang and Sun.
FAU - Zhang, Chen Qi
AU  - Zhang CQ
AD  - Department of Special-Need Medical, Chengdu BOE Hospital, Chengdu, China.
FAU - Li, Hong Yan
AU  - Li HY
AD  - Department of Special-Need Medical, Chengdu BOE Hospital, Chengdu, China.
FAU - Wan, Yong
AU  - Wan Y
AD  - Department of Special-Need Medical, Chengdu BOE Hospital, Chengdu, China.
FAU - Bai, Xue Yang
AU  - Bai XY
AD  - Department of Special-Need Medical, Chengdu BOE Hospital, Chengdu, China.
FAU - Gan, Lu
AU  - Gan L
AD  - Department of Special-Need Medical, Chengdu BOE Hospital, Chengdu, China.
FAU - Wang, Juan
AU  - Wang J
AD  - Department of Special-Need Medical, Chengdu BOE Hospital, Chengdu, China.
FAU - Sun, Hong Bin
AU  - Sun HB
AD  - Department of Neurology, Sichuan Academy of Medical Sciences and Sichuan 
      Provincial People's Hospital, Chengdu, China.
LA  - eng
PT  - Systematic Review
DEP - 20220405
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9037144
OTO - NOTNLM
OT  - divalproex
OT  - efficacy
OT  - extended release
OT  - meta-analysis
OT  - safety
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/29 06:00
MHDA- 2022/04/29 06:01
PMCR- 2022/04/05
CRDT- 2022/04/28 06:18
PHST- 2021/11/25 00:00 [received]
PHST- 2022/02/23 00:00 [accepted]
PHST- 2022/04/28 06:18 [entrez]
PHST- 2022/04/29 06:00 [pubmed]
PHST- 2022/04/29 06:01 [medline]
PHST- 2022/04/05 00:00 [pmc-release]
AID - 811017 [pii]
AID - 10.3389/fphar.2022.811017 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Apr 5;13:811017. doi: 10.3389/fphar.2022.811017. 
      eCollection 2022.