TY - JOUR
T1 - Differences in the prophylactic effect of serum lithium levels on depression and mania in bipolar disorder
T2 - A dose-response meta-analysis
AU - Hsu, Chih Wei
AU - Tsai, Shang Ying
AU - Tseng, Ping Tao
AU - Liang, Chih Sung
AU - Vieta, Eduard
AU - Carvalho, Andre F.
AU - Stubbs, Brendon
AU - Kao, Hung Yu
AU - Tu, Yu Kang
AU - Lin, Pao Yen
N1 - Publisher Copyright:
© 2022 Elsevier B.V. and ECNP
PY - 2022/5
Y1 - 2022/5
N2 - 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.
AB - 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.
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U2 - 10.1016/j.euroneuro.2022.01.112
DO - 10.1016/j.euroneuro.2022.01.112
M3 - Article
C2 - 35158229
AN - SCOPUS:85124414561
SN - 0924-977X
VL - 58
SP - 20
EP - 29
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
ER -