2005-cipriani.pdf: “Lithium in the Prevention of Suicidal Behavior and All-Cause Mortality in Patients With Mood Disorders: A Systematic Review of Randomized Trials”, Andrea Cipriani, Heather Pretty, Keith Hawton, John R. Geddes (2005-10-01):
Objective: Observational studies suggest that long-term lithium treatment has a strong antisuicidal effect in mood disorders, but it is uncertain whether this association is a genuine therapeutic effect or is due to confounding factors in nonrandomized studies. The authors conducted a systematic review and meta-analysis of randomized trials to investigate the effect of lithium, compared to placebo and other active treatments, on the risk of suicide, deliberate self-harm, and all-cause mortality in patients with mood disorder.
Method: The data source was the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register, incorporating results of searches of MEDLINE (1966–June 2002), EMBASE (1980–June 2002), CINAHL (1982–March 2001), PsycLIT (1974–June 2002), PSYNDEX (1977–October 1999), and LILACS (1982–March 2001). The Cochrane Central Register of Controlled Trials (CENTRAL) was searched with the term “lithium” for new records entered into the database from 1999 to 2003. Studies selected included randomized, controlled trials comparing lithium with placebo or all other compounds used in long-term treatment for mood disorders (unipolar depression, bipolar disorder, schizoaffective disorder, dysthymia, and rapid cycling, diagnosed according to DSM or ICD criteria). Of 727 references identified in the search, 52 articles were marked as possibly relevant on the basis of the abstract, and 32 randomized, controlled trials were eligible for inclusion in the review. Two independent reviewers extracted the data, and disagreements were resolved by consensus with a third reviewer. Methodological quality was assessed according to the criteria of the Cochrane Collaboration. When the outcomes of interest were not reported, an attempt was made to obtain the required data from the original authors.
Results: In 32 trials, 1,389 patients were randomly assigned to receive lithium and 2,069 to receive other compounds. Patients who received lithium were less likely to die by suicide (data from seven trials; two versus 11 suicides; odds ratio = 0.26; 95% confidence interval [CI] = 0.09–0.77). The composite measure of suicide plus deliberate self-harm was also lower in patients who received lithium (odds ratio = 0.21; 95% CI = 0.08–0.50). There were fewer deaths overall in patients who received lithium (data from 11 trials; nine versus 22 deaths; odds ratio = 0.42, 95% CI = 0.21–0.87).
Conclusions: Lithium is effective in the prevention of suicide, deliberate self-harm, and death from all causes in patients with mood disorders.
2009-ohgami.pdf: “Lithium levels in drinking water and risk of suicide”, Hirochika Ohgami, Takeshi Terao, Ippei Shiotsuki, Nobuyoshi Ishii, Noboru Iwat (2009-05-01):
Although lithium is known to prevent suicide in people with mood disorders, it is uncertain whether lithium in drinking water could also help lower the risk in the general population. To investigate this, we examined lithium levels in tap water in the 18 municipalities of Oita prefecture in Japan in relation to the suicide standardised mortality ratio (SMR) in each municipality. We found that lithium levels were statistically-significantly and negatively associated with SMR averages for 2002–2006. These findings suggest that even very low levels of lithium in drinking water may play a role in reducing suicide risk within the general population.
2014-mauer.pdf: “Standard and trace-dose lithium: A systematic review of dementia prevention and other behavioral benefits”, Sivan Mauer, Derick Vergne, S. Nassir Ghaemi (2014-06-11):
Objective: Dementia is a major public health issue, with notably high rates in persons with mood illnesses. Lithium has been shown to have considerable neuroprotective effects, even in trace or low doses. The aim of this review is to summarize the current understanding of lithium benefits in trace or low doses in dementia prevention and for other behavioral or medical benefits.
Methods: A systematic review identified 24 clinical, epidemiological, and biological reports that met inclusion criteria of assessing lithium in standard or low doses for dementia or other behavioral or medical benefits.
Results: 5 out of 7 epidemiological studies found an association between standard-dose lithium and low dementia rates. 9 out of 11 epidemiological studies, usually of drinking water sources, found an association between trace-dose lithium and low suicide/
homicide/ mortality and crime rates. All four small randomized clinical trials of lithium for Alzheimer’s dementia have found at least some clinical or biological benefits versus placebo. Only one small randomized clinical trial (RCT) of trace lithium has been conducted, assessing mood symptoms in former substance abusers, and found benefit with lithium versus placebo.
Conclusions: Lithium, in both standard and trace doses, appears to have biological benefits for dementia, suicide, and other behavioral outcomes. Further RCT research of trace lithium in dementia is warranted. [Keywords: Cognition, dementia, lithium, prevention, standard dose, trace]
2018-fajardo.pdf: “Trace lithium in Texas tap water is negatively associated with all-cause mortality and premature death”, Val A. Fajardo, Paul J. LeBlanc, Val Andrei Fajardo (2018):
Lithium in tap water was previously found to have life-extending effects across 18 Japanese municipalities. Using a larger dataset with several Texas counties, our study shows that lithium concentrations in tap water are negatively associated with all-cause mortality (r = −0.18, p = 0.006, 232 counties) and years of potential life lost (r = −0.22, p = 0.001, 214 counties). Thus, our present findings extend and reinforce lithium’s purported life-prolonging effect in humans.
2018-palmer.pdf: “The Association Between Lithium in Drinking Water and Incidence of Suicide Across 15 Alabama Counties”, Anna Palmer, Marshall E. Cates, Greg Gorman (2018):
Background: Recent studies have shown that lithium may be effective at reducing suicide at low doses, such as those found in drinking water.
Aims: The purpose of this study was to compare suicide rates with natural lithium levels in the drinking water of various Alabama counties.
Method: Five drinking water samples from each of 15 Alabama counties were collected. Lithium levels were measured in triplicate using an inductively coupled plasma emission spectrophotometer and compared with suicide rate data for the period 1999–2013. Age, gender, and poverty were evaluated as potential confounding variables.
Results: The average measured lithium concentrations ranged from 0.4 ppb to 32.9 ppb between the counties tested. The plot of suicide rate versus lithium concentration showed a statistically-significant inverse relationship (r = −0.6286, p = 0.0141). Evaluation of male-only suicide rate versus lithium concentration data also yielded statistically-significant results; however, the female-only rate was not statistically-significant. Age standardized suicide rates and poverty when individually compared against lithium levels were also found to be statistically-significant; unexpectedly, however, poverty had a parallel trend with suicide rate.
Conclusion: Lithium concentration in drinking water is inversely correlated with suicide rate in 15 Alabama counties.
2019-ng.pdf: “Adding Lithium to Drinking Water for Suicide Prevention—The Ethics”, Jared Ng, Manne Sjöstrand, Nir Eyal (2019):
Recent observations associate naturally occurring trace levels of Lithium in ground water with statistically-significantly lower suicide rates. It has been suggested that adding trace Lithium to drinking water could be a safe and effective way to reduce suicide. This article discusses the many ethical implications of such population-wide Lithium medication. It compares this policy to more targeted solutions that introduce trace amounts of Lithium to groups at higher risk of suicide or lower risk of adverse effects. The question of mass treatment with Lithium recalls other choices in public health between population-wide and more targeted interventions. The framework we propose could be relevant to some of these other dilemmas.
2020-eyrewatt.pdf: “The association between lithium in drinking water and neuropsychiatric outcomes: A systematic review and meta-analysis from across 2678 regions containing 113 million”, Brenton Eyre-Watt, Eesharnan Mahendran, Shuichi Suetani, Joseph Firth, Steve Kisely, Dan Siskind (2020-10-13):
Background: Lithium in drinking water may have substantial 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 statistically-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. [Keywords: Neuropsychiatric outcomes, lithium, drinking water, suicide, public health]
2020-kugimiya.pdf: “Lithium in drinking water and suicide prevention: The largest nationwide epidemiological study from Japan”, Tsuyoshi Kugimiya, Nobuyoshi Ishii, Kentaro Kohno, Masayuki Kanehisa, Koji Hatano, Hirofumi Hirakawa, Takeshi Terao (2020-08-11):
Objectives: The aims of the present study thus were (a) to further investigate the association between lithium levels in drinking water and suicide rates by adjusting relevant factors using the so far largest available dataset in Japan, (b) to confirm sex differences, (c) to estimate the effects of long-term exposure to trace lithium, (d) to investigate the effects of drinking bottled instead of tap water, and (e) to exploratorily investigate which lithium levels may be associated with lower suicide rates.
Methods: Mean lithium levels in drinking water of all 808 cities and wards (ie, 785 cities of 46 prefectures and 23 wards of Tokyo) in Japan were examined in relation to mean suicide standardized mortality ratios (SMRs) during the 7 years from 2010 to 2016. Multiple regression analyses adjusted for the size of each population were used to investigate the association of lithium levels with suicide SMRs with adjustments for relevant factors.
Results: The adjusted model showed statistically-significant inverse associations of lithium levels with total and male SMRs, but not with female SMRs. Neither the proportion of residents who continued to live in the same city nor the consumption of bottled water changed the association between lithium levels and suicide SMRs. Finally, it was 30 μg/
L or more that was associated with lower suicide SMRs.
Conclusions: The present findings reconfirm the inverse association between lithium levels in drinking water and suicide rates particularly in the male population.
2020-memon.pdf: “Association between naturally occurring lithium in drinking water and suicide rates: systematic review and meta-analysis of ecological studies”, Anjum Memon, Imogen Rogers, Sophie M. D. D. Fitzsimmons, Ben Carter, Rebecca Strawbridge, Diego Hidalgo-Mazzei, Allan H. Young (2020-07-27):
Background: The prevalence of mental health conditions and national suicide rates are increasing in many countries. Lithium is widely and effectively used in pharmacological doses for the treatment and prevention of manic/
depressive episodes, stabilising mood and reducing the risk of suicide. Since the 1990s, several ecological studies have tested the hypothesis that trace doses of naturally occurring lithium in drinking water may have a protective effect against suicide in the general population.
Aims: To synthesise the global evidence on the association between lithium levels in drinking water and suicide mortality rates.
Method: The MEDLINE, Embase, Web of Science and PsycINFO databases were searched to identify eligible ecological studies published between 1 January 1946 and 10 September 2018. Standardised regression coefficients for total (i.e. both genders combined), male and female suicide mortality rates were extracted and pooled using random-effects meta-analysis. The study was registered with PROSPERO (CRD42016041375).
Results: The literature search identified 415 articles; of these, 15 ecological studies were included in the synthesis. The random-effects meta-analysis showed a consistent protective (or inverse) association between lithium levels/
concentration in publicly available drinking water and total (pooled β = −0.27, 95% CI −0.47 to −0.08; p = 0.006, I2 = 83.3%), male (pooled β = −0.26, 95% CI −0.56 to 0.03; p = 0.08, I2 = 91.9%) and female (pooled β = −0.13, 95% CI −0.24 to −0.02; p = 0.03, I2 = 28.5%) suicide mortality rates. A similar protective association was observed in the six studies included in the narrative synthesis, and subgroup meta-analyses based on the higher/ lower suicide mortality rates and lithium levels/ concentration.
Conclusions: This synthesis of ecological studies, which are subject to the ecological fallacy/
bias, supports the hypothesis that there is a protective (or inverse) association between lithium intakes from public drinking water and suicide mortality at the population level. Naturally occurring lithium in drinking water may have the potential to reduce the risk of suicide and may possibly help in mood stabilisation, particularly in populations with relatively high suicide rates and geographical areas with a greater range of lithium concentration in the drinking water. All the available evidence suggests that randomised community trials of lithium supplementation of the water supply might be a means of testing the hypothesis, particularly in communities (or settings) with demonstrated high prevalence of mental health conditions, violent criminal behaviour, chronic substance misuse and risk of suicide.
2021-lindsey.pdf: “Lithium in groundwater used for drinking–water supply in the United States”, Bruce D. Lindsey, Kenneth Belitz, Charles A. Cravotta III, Patricia L. Toccalino, Neil M. Dubrovsky (2021-05-01):
- Lithium in groundwater has not been comprehensively evaluated in the US.
- Concentrations in groundwater frequently exceed the human-health benchmark.
- The distribution of lithium concentrations varies widely by lithology and climate.
- Higher lithium concentrations are found in arid regions and older groundwater.
- Cation exchange or mixing with saline water lead to highest concentrations.
Lithium concentrations in untreated groundwater from 1464 public-supply wells and 1676 domestic-supply wells distributed across 33 principal aquifers in the United States were evaluated for spatial variations and possible explanatory factors.
Concentrations nationwide ranged from <1 to 396 μg/
L (median of 8.1) for public supply wells and <1 to 1700 μg/ L (median of 6 μg/ L) for domestic supply wells. For context, lithium concentrations were compared to a Health Based Screening Level (HBSL, 10 μg/ L) and a drinking-water only threshold (60 μg/ L). These thresholds were exceeded in 45% and 9% of samples from public-supply wells and in 37% and 6% from domestic-supply wells, respectively. However, exceedances and median concentrations ranged broadly across geographic regions and principal aquifers.
Concentrations were highest in arid regions and older groundwater, particularly in unconsolidated clastic aquifers and sandstones, and lowest in carbonate-rock aquifers, consistent with differences in lithium abundance among major lithologies and rock weathering extent. The median concentration for public-supply wells in the unconsolidated clastic High Plains aquifer (central United States) was 24.6 μg/
L; 24% of the wells exceeded the drinking-water only threshold and 86% exceeded the HBSL. Other unconsolidated clastic aquifers in the arid West had exceedance rates comparable to the High Plains aquifer, whereas no public supply wells in the Biscayne aquifer (southern Florida) exceeded either threshold, and the highest concentration in that aquifer was 2.6 μg/ L.
Multiple lines of evidence indicate natural sources for the lithium concentrations; however, anthropogenic sources may be important in the future because of the rapid increase of lithium battery use and subsequent disposal. Geochemical models demonstrate that extensive evaporation, mineral dissolution, cation exchange, and mixing with geothermal waters or brines may account for the observed lithium and associated constituent concentrations, with the latter two processes as major contributing factors.
2021-steinmetz.pdf: “Lithium in drinking water, altitude, and suicide rates in rural areas of Argentinean Andes”, Lorena Cecilia López Steinmetz, Romina Lucrecia, López Steinmetz, Silvina Laura Diaz, Juan Carlos Godoy (2021-02-01):
The Lithium Triangle in the Andean plateau involves high altitude (>3,000 m asl) hydrological systems having high lithium graded waters. This research was carried-out in rural areas of north westernmost Argentinean Andes and was aimed: (1) to determine concentrations of lithium in drinking waters; (2) to calculate suicide mortality rates based on available official data (2003–2013); (3) to analyze bivariate differences between lithium concentrations in drinking water, mean rates of suicide mortality, altitude of sampling sites, and water sources; (4) to analyze bivariate correlations between lithium concentrations in drinking water, mean rates of suicide mortality, and altitude; (5) to test predictive models for mean rates of suicide mortality, when considering the predictors lithium concentrations in drinking water, altitude, and water sources.
Lithium determinations in drinking waters were performed by Microwave Plasma-Atomic Emission Spectrometer. Nonparametric tests were applied to analyze differences and correlations. Generalized linear models (GLM) were used to fitting models for mean rates of suicide. Drinking waters contained up to 2.98 mg L−1 of lithium. Mean rates of suicide mortality (per 100,000 inhabitants) were high, ranging from 19.12 (± 19.83) to 30.22 (± 16.70). Lithium but not altitude was positively correlated with suicide mortality when analyzing bivariate correlations (Li: ρ = 0.76, p < 0.001). However, when GLM were calculated, a statistically-significant interaction effect was found between lithium and altitude (p < 0.001). This interaction effect would act in some way restraining the suicide mortality rates. [Keywords: lithium in drinking water, altitude, suicide, rural populations, Andes, Argentina]