ArticleEClinicalMedicine2022
Comparative effectiveness of valproic acid in different serum concentrations for maintenance treatment of bipolar disorder: A retrospective cohort study using target trial emulation framework.
Article in EClinicalMedicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials: A Systematic Review.JAMA network open · 2023Pooled it
- From study design to executable code: automating target trial emulation with large language models.JAMIA open · 2026Article
- Association between maintenance doses of mood stabilizers and antipsychotics and risk of readmission in first-episode bipolar disorder.Molecular psychiatry · 2026Article
- Design and Implementation of Observational Studies Emulating a Target Trial.JAMA network open · 2026Article
- Bipolar disorder.Lancet (London, England) · 2025Review
- Outpatient Management of Bipolar Disorder in Older Adults.Current psychiatry reports · 2025Review
- Article
- Optimising the use of electronic medical records for large scale research in psychiatry.Translational psychiatry · 2024Review
- Effects of Sex Differences and Combined Use of Clozapine on Initial Dosage Optimization of Valproic Acid in Patients with Bipolar Disorder.Current pharmaceutical design · 2024Article
- Mortality and Lithium-Protective Effects after First-Episode Mania Diagnosis in Bipolar Disorder: A Nationwide Retrospective Cohort Study in Taiwan.Psychotherapy and psychosomatics · 2024Article
- Therapeutic and Toxic Effects of Valproic Acid Metabolites.Metabolites · 2023Review
- Predicting new-onset post-stroke depression from real-world data using machine learning algorithm.Frontiers in psychiatry · 2023Article
Corrections and comments
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Authors and funding
12 authors at 9 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: There is a lack of consensus on the optimal serum valproic acid (VPA) concentration for maintenance therapy in bipolar disorder (BD). We aimed to investigate the association between serum VPA levels and risk of mood episode recurrence. Methods: We enrolled patients with BD from multiple medical institutions in Taiwan between January 1, 2001 and December 31, 2019. Patients were divided into three groups according to their serum VPA concentrations (< 50 μg/ml, 50-74 μg/ml, and 75-104 μg/ml). Adjusted hazard ratios (aHR) with 95% confidence intervals (CIs) compared times to mood episode recurrence using the < 50 μg/ml group as reference. A systematic review found relevant articles published before February 2022 (PROSPERO: CRD42022309661), and corresponding results were compared. Findings: This cohort included 896 patients for an intention-to-treat analysis. Compared with the < 50 μg/ml group, a non-significantly lower risk of mood episode recurrence was found in the 50-74 μg/ml (aHR, 95% CI: 0·86, 0·71-1·05) and 75-104 μg/ml (0·91, 0·71-1·18) groups. A per-protocol analysis of 481 patients found a significant risk reduction in the 50-74 μg/ml group (0·76, 0·60-0·97), with inconclusive results in the ≥ 75 μg/ml group (1·03, 0·73-1·46). A meta-analysis including two studies (254 patients) and our cohort found a similar significantly lower risk of mood episode recurrence in the 50-74 μg/ml group (HR, 95% CI: 0·83, 0·69-0·99), while risk reduction in the 75-99 μg/ml group (0·62, 0·26-1·48) did not differ significantly from that in the < 50 μg/ml group or the 50-74 μg/ml group. Interpretation: The combined results of this cohort and previous studies suggest that VPA between 50-74 μg/ml may be a more effective concentration to prevent acute mood episodes during maintenance therapy in patients with BD compared with VPA < 50 μg/ml. Funding: Ministry of Science and Technology, Taiwan, and Chang Gung Medical Research Project.
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