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

Yang-Chieh Brian Chen; Chih-Sung Liang; Liang-Jen Wang; Kuo-Chuan Hung; Andre F. Carvalho; Marco Solmi; Eduard Vieta; Ping-Tao Tseng; Pao-Yen Lin; Yu-Kang Tu; Chih-Wei Hsu; Edward Chia-Cheng Lai

EClinicalMedicine (Dec 2022)

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

Yang-Chieh Brian Chen,
Chih-Sung Liang,
Liang-Jen Wang,
Kuo-Chuan Hung,
Andre F. Carvalho,
Marco Solmi,
Eduard Vieta,
Ping-Tao Tseng,
Pao-Yen Lin,
Yu-Kang Tu,
Chih-Wei Hsu,
Edward Chia-Cheng Lai

Affiliations

Yang-Chieh Brian Chen: Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Chih-Sung Liang: Department of Psychiatry, Beitou branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Psychiatry, National Defense Medical Center, Taipei, Taiwan
Liang-Jen Wang: Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Kuo-Chuan Hung: Department of Anesthesiology, Chi Mei Medical Center, Tainan city, Taiwan; Department of Hospital and Health Care Administration, College of Recreation and Health Management, Chia Nan University of Pharmacy and Science, Tainan city, Taiwan
Andre F. Carvalho: IMPACT (Innovation in Mental and Physical Health and Clinical Treatment) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia
Marco Solmi: Department of Psychiatry, University of Ottawa, Ottawa, Canada; Department of Mental Health, The Ottawa Hospital, Ottawa, Canada; Ottawa Hospital Research Institute (OHRI), Clinical Epidemiology Program, University of Ottawa, Ottawa, Canada; School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Canada; Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany
Eduard Vieta: Bipolar and Depressive Disorders Unit, Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, Barcelona, Catalonia, Spain
Ping-Tao Tseng: Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan; Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan
Pao-Yen Lin: Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Yu-Kang Tu: Institute of Epidemiology and Preventive Medicine, National Taiwan University College of Public Health, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan
Chih-Wei Hsu: Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Computer Science and Information Engineering, National Cheng Kung University, Tainan, Taiwan; Corresponding author at: Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, No. 123, Dapi Road, Niaosong District, Kaohsiung City 833, Taiwan.
Edward Chia-Cheng Lai: School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Journal volume & issue: Vol. 54
p. 101678

Abstract

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Summary: 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.

Published in EClinicalMedicine

ISSN: 2589-5370 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Medicine (General)
Website: https://www.thelancet.com/journals/eclinm/home

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