Differences in the prophylactic effect of serum lithium levels on depression and mania in bipolar disorder: A dose-response meta-analysis

Chih Wei Hsu, Shang Ying Tsai, Ping Tao Tseng, Chih Sung Liang, Eduard Vieta, Andre F. Carvalho, Brendon Stubbs, Hung Yu Kao, Yu Kang Tu, Pao Yen Lin

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

The optimal serum lithium levels for preventing the recurrence of mood episodes in bipolar disorder are controversial, especially when polarity is considered. The present study aimed to comprehensively examine the dose-response relationship between lithium concentration and risk of recurrence of mood episodes. We conducted a systematic search of major databases before January 2021 (PROSPERO: CRD42021235812). A one-stage, random-effects, restricted cubic splines model was used to estimate the dose-response relationship between lithium concentration and risk of recurrence of any or specific mood episodes (depression or mania). The effect size is shown as odds ratio (OR). Our meta-analysis included six randomised controlled trials with a total of 975 participants. The dose-response curve showed that increased serum concentrations were associated with a gradual decrease in the risk of any mood episodes (OR 0.50 at 0.60 mmol/l, OR 0.15 at 1.20 mmol/l). The risk of depression decreased slightly with a concentration of 0.60 mmol/l (OR 0.83) but dropped rapidly as the concentration increased to 1.20 mmol/l (OR 0.39). By contrast, the risk for mania initially decreased steadily (OR 0.44), but decreased only marginally (OR 0.30) as the concentration increased. To reduce the recurrence risk to 56%, prevention of depression required a higher concentration than that required for mania (1.13 mmol/l vs. 0.60 mmol/l). Our results suggest a negative dose-response relationship between serum lithium levels and risk of recurrence. In particular, the different preventive effects of serum concentration on depression and mania will be an important clinical reference.

Original languageEnglish
Pages (from-to)20-29
Number of pages10
JournalEuropean Neuropsychopharmacology
Volume58
DOIs
Publication statusPublished - May 2022

Keywords

  • Bipolar disorder
  • Dose-response meta-analysis
  • Lithium
  • Maintenance
  • Polarity
  • Serum level

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

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