@article{2897803114b94b9b8c5d08f050735300,
title = "Lithium concentration and recurrence risk during maintenance treatment of bipolar disorder: Multicenter cohort and meta-analysis",
abstract = "Objective: To compare differences in efficacy during maintenance treatment for bipolar disorder (BD) according to lithium serum levels. A multicenter retrospective cohort study and a dose-response meta-analysis were conducted. Methods: The cohort study was conducted in Taiwan from 2001 to 2019 to identify patients with euthymic BD according to different serum levels (<0.4, 0.4–0.8, and 0.8–1.2 mmol/L). We adopted adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for time to the recurrence of mood episodes having the <0.4 mmol/L group as the reference group. Moreover, we systematically searched for related articles in major databases before January 31, 2021 (PROSPERO: CRD42021235812). We used random-effects modeling to estimate the dose-response relationships between lithium serum levels and recurrence of mood episodes, which were depicted as odds ratios (ORs) with 95% CIs. Results: A total of 1406 participants (cohort: 466; meta-analysis: 940) were included. In the cohort study, the 0.4–0.8 mmol/L group was associated with a significantly lower risk of recurrences (aHR: 0.75), while the 0.8–1.2 mmol/L group had a lower risk without statistical significance (aHR: 0.77). The dose-response meta-analysis showed that with the increase in lithium serum levels, the risk decreased (linear model OR: 0.85, for every 0.1 mmol/L increase; non-linear model OR: 1.00 at 0.0 mmol/L, 0.42 at 0.4 mmol/L, and 0.27 at 0.8 mmol/L). Conclusion: Although confounding by indication cannot be excluded, the combined results suggest a significant preventative effect on the recurrence of major affective episodes among those with serum levels of 0.4–0.8 mmol/L.",
keywords = "bipolar disorder, dose-response meta-analysis, lithium, maintenance treatment, serum level",
author = "Hsu, {Chih Wei} and Carvalho, {Andre F.} and Tsai, {Shang Ying} and Wang, {Liang Jen} and Tseng, {Ping Tao} and Lin, {Pao Yen} and Tu, {Yu Kang} and Eduard Vieta and Marco Solmi and Hung, {Chi Fa} and Kao, {Hung Yu}",
note = "Funding Information: The authors would like to thank Ms. Pei‐Ying Yang, Mr. Chien‐An Hu, and the Institute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University for the technical support. This study is supported by grants from the Ministry of Science and Technology, Taiwan (MOST 109‐2314‐B‐182A‐009‐MY2), and the funding sources had no role in the design of the study. The detailed author contributions are as follows CW Hsu and AF Carvalho involved in research idea and study design. data acquisition: CW Hsu for cohort, CW Hsu and PT Tseng for meta‐analysis; CW Hsu, AF Carvalho, LJ Wang, and M Solmi involved in data interpretation. CW Hsu involved in statistical analysis and manuscript drafting. CW Hsu, AF Carvalho, SY Tsai, LJ Wang, PT Tseng, PY Lin, YK Tu, E Vieta, M Solmi, CF Hung, and HY Kao involved in manuscript revision. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. Funding Information: Prof. Vieta has received grants and served as a consultant, advisor, or CME speaker for the following entities: AB‐Biotics, Abbott, Allergan, Angelini, AstraZeneca, Bristol‐Myers Squibb, Dainippon Sumitomo Pharma, Farmindustria, Ferrer, Forest Research Institute, Gedeon Richter, Glaxo‐Smith‐Kline, Janssen, Lundbeck, Otsuka, Pfizer, Roche, SAGE, Sanofi‐Aventis, Servier, Shire, Sunovion, Takeda, the Brain and Behaviour Foundation, the Spanish Ministry of Science and Innovation (CIBERSAM), the EU Horizon 2020 and the Stanley Medical Research Institute. Other authors declare no financial interests or potential conflicts of interest regarding the authorship and publication of this article. Funding Information: The authors would like to thank Ms. Pei-Ying Yang, Mr. Chien-An Hu, and the Institute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University for the technical support. This study is supported by grants from the Ministry of Science and Technology, Taiwan (MOST 109-2314-B-182A-009-MY2), and the funding sources had no role in the design of the study. The detailed author contributions are as follows CW Hsu and AF Carvalho involved in research idea and study design. data acquisition: CW Hsu for cohort, CW Hsu and PT Tseng for meta-analysis; CW Hsu, AF Carvalho, LJ Wang, and M Solmi involved in data interpretation. CW Hsu involved in statistical analysis and manuscript drafting. CW Hsu, AF Carvalho, SY Tsai, LJ Wang, PT Tseng, PY Lin, YK Tu, E Vieta, M Solmi, CF Hung, and HY Kao involved in manuscript revision. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. Publisher Copyright: {\textcopyright} 2021 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.",
year = "2021",
month = oct,
doi = "10.1111/acps.13346",
language = "English",
volume = "144",
pages = "368--378",
journal = "Acta Psychiatrica Scandinavica",
issn = "0001-690X",
publisher = "Wiley-Blackwell",
number = "4",
}
