Lithium concentration and recurrence risk during maintenance treatment of bipolar disorder: Multicenter cohort and meta‐analysis

• Published in: Acta psychiatrica Scandinavica Vol. 144; no. 4; pp. 368 - 378
• Main Authors: Hsu, Chih‐Wei, Carvalho, Andre F., Tsai, Shang‐Ying, Wang, Liang‐Jen, Tseng, Ping‐Tao, Lin, Pao‐Yen, Tu, Yu‐Kang, Vieta, Eduard, Solmi, Marco, Hung, Chi‐Fa, Kao, Hung‐Yu
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.10.2021; John Wiley and Sons Inc
• Subjects: Antimanic Agents - therapeutic use; Bipolar disorder; Bipolar Disorder - drug therapy; Bipolar Disorder - epidemiology; Cohort Studies; dose‐response meta‐analysis; Drug dosages; Humans; Lithium; Lithium - therapeutic use; maintenance treatment; Meta-analysis; Mood; Original; Recurrence; Retrospective Studies; Risk; serum level; Serum levels; serum level; dose-response meta-analysis; lithium; bipolar disorder; maintenance treatment
• ISSN: 0001-690X; 1600-0447; 1600-0447
• DOI: 10.1111/acps.13346

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.