The association between lithium in drinking water and neuropsychiatric outcomes: A systematic review and meta-analysis from across 2678 regions containing 113 million people

Abstract

Background: Lithium in drinking water may have significant mental health benefits. We investigated the evidence on the association between lithium concentrations in drinking water and their neuropsychiatric outcomes. Methods: We conducted a systematic review and meta-analysis and searched Pubmed, Embase, Web of Science, PsycINFO and CINAHL up to 19 January 2020, for peer-reviewed research examining the association between lithium concentrations in drinking water and neuropsychiatric outcomes. We used a pairwise analysis and a random effects model to meta-analyse suicide rates and psychiatric hospital admissions. We assessed for publication bias using Egger’s test and Duval and Tweedie’s Trim and Fill analysis. Results: Twenty-seven studies including 113 million subjects were included in this systematic review. Meta-analysis of 14 studies including 94 million people found higher lithium concentrations were associated with reduced suicide rates ( r = −0.191, 95% confidence interval = [−0.287, −0.090], p < 0.001) and meta-analysis of two studies including 5 million people found higher lithium concentrations were associated with fewer hospital admissions ( r = −0.413, 95% confidence interval = [−0.689, −0.031], p = 0.035). We found significant heterogeneity between studies ( Q = 67.4, p < 0.001, I2 = 80.7%) and the presence of publication bias (Egger’s test; t value = 2.90, p = 0.013). Other included studies did not provide sufficient data to analyse other neuropsychiatric outcomes quantitatively. Conclusion: Higher lithium concentrations in drinking water may be associated with reduced suicide rates and inpatient psychiatric admissions. The relationship with other neuropsychiatric outcomes and complications remains unclear. Further research is required before any public health recommendations can be made. Trial registration number: The study was registered with PROSPERO, number CRD42018090145.

Comparison of lithium levels between suicide and non-suicide fatalities: Cross-sectional study

“…As expected, the lithium concentration in the aqueous humor reflected that in the serum and did not significantly change after death. This result is consistent with previous ecological studies showing an inverse correlation between regional lithium concentration in drinking water and suicide rate [15]. The findings of the present study also accord with those of a previous study, suggesting that the lithium concentration in the brain is lower in suicide than in a non-suicide victim [20].…”

Effects of lithium on suicide and suicidal behaviour: a systematic review and meta-analysis of randomised trials

“…This challenges the results of previous meta-analyses of randomised trials (Cipriani et al ., 2013 ; Smith and Cipriani, 2017 ), guideline recommendations (Veterans Affairs and Department of Defence, (2019 ) and the longstanding consensus that lithium reduces the risk of suicide. It contrasts with ecological studies that find associations between lithium levels in drinking water and suicide rates, suggesting they may have been influenced by publication bias, which is evident in some reviews (Eyre-Watt et al ., 2021 ). In contrast, our results are consistent with a previous systematic review, although this only included a single trial (Borjesson and Gotzsche, 2019 ), with an earlier Cochrane review published in 2001, which included four trials in total, two of which were included in the meta-analysis (Burgess et al ., 2001 ), and with the fact that the largest trial of lithium for suicide prevention, published in 2021, was terminated early due to lack of effect (Katz et al ., 2022 ).…”

“…An influential meta-analysis of randomised trials also concluded that lithium can reduce the risk of suicide (Cipriani et al ., 2013 ). Moreover, ecological analyses have reported associations between lithium levels in drinking water and lower suicide rates (Memon et al ., 2020 ), although publication bias and heterogeneity are noted as limitations in the latest meta-analysis of these studies (Eyre-Watt et al ., 2021 ). Thus, despite some recent analyses coming to different conclusions (Riblet et al ., 2017 ; Borjesson and Gotzsche, 2019 ), many researchers and clinicians regard lithium's anti-suicidal properties as ‘proven’ (Lewitzka et al ., 2015a , p. 1) by ‘unambiguous evidence’ (Lewitzka et al ., 2015b , p. 1).…”

Lithium isotopes in the Loire River Basin (France): Hydrogeochemical characterizations at two complementary scales

“…This study can be considered as pioneering, since Li is found naturally in drinking water (Eyre-Watt et al, 2020;Ewuzie et al, 2020) with various origins. In clinical practice, it is widely used in the treatment of bipolar and of mood disorders.…”