Comparative effectiveness of valproic acid in different serum concentrations for maintenance treatment of bipolar disorder: A retrospective cohort study using target trial emulation framework

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Title:	Comparative effectiveness of valproic acid in different serum concentrations for maintenance treatment of bipolar disorder: A retrospective cohort study using target trial emulation framework
Authors:	Chen, Yang-Chieh Brian Liang, Chih-Sung Wang, Liang-Jen Hung, Kuo-Chuan Carvalho, Andre F. Solmi, Marco Vieta, Eduard Tseng, Ping-Tao Lin, Pao -Yen Tu, Yu-Kang Hsu, Chih-Wei Lai, Edward Chia-Cheng
Contributors:	Chang Gung Memorial Hospital Chang Gung University Tri-Service General Hospital National Defense Medical Center Chang Gung University Chang Gung Memorial Hospital Chi Mei Hospital Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy & Science Deakin University University of Ottawa Ottawa Hospital Research Institute University of Ottawa Ottawa Hospital Research Institute Free University of Berlin Humboldt University of Berlin Charite Universitatsmedizin Berlin University of Barcelona Hospital Clinic de Barcelona IDIBAPS CIBER - Centro de Investigacion Biomedica en Red CIBERSAM National Sun Yat Sen University Asia University Taiwan Chang Gung Memorial Hospital National Taiwan University National Taiwan University National Taiwan University Hospital National Cheng Kung University National Cheng Kung University Chang Gung Memorial Hospital
Keywords:	lithium levels pharmacokinetics divalproex psychiatry binding
Date:	2022
Issue Date:	2023-12-11 13:58:45 (UTC+8)
Publisher:	ELSEVIER
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 mu g/ ml, 50-74 mu g/ml, and 75-104 mu g/ml). Adjusted hazard ratios (aHR) with 95% confidence intervals (CIs) compared times to mood episode recurrence using the < 50 mu g/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 mu g/ml group, a non-significantly lower risk of mood episode recurrence was found in the 50-74 mu g/ml (aHR, 95% CI: 0.86, 0.71 -1.05) and 75-104 mu g/ml (0.91, 0.71-1.18) groups. A per-protocol analysis of 481 patients found a significant risk reduction in the 50-74 mu g/ml group (0.76, 0.60-0.97), with inconclusive results in the >= 75 mu g/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 mu g/ml group (HR, 95% CI: 0.83, 0.69-0.99), while risk reduction in the 75-99 mu g/ml group (0.62, 0.26-1.48) did not differ significantly from that in the < 50 mu g/ml group or the 50-74 mu g/ml group.Interpretation The combined results of this cohort and previous studies suggest that VPA between 50-74 mu g/ml may be a more effective concentration to prevent acute mood episodes during maintenance therapy in patients with BD compared with VPA < 50 mu g/ml.Funding Ministry of Science and Technology, Taiwan, and Chang Gung Medical Research Project.Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Relation:	ECLINICALMEDICINE, v.54, 101678
Appears in Collections:	[Dept. of Hospital and Health (including master's program)] Periodical Articles

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