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“Association between Lithium Levels in Drinking Water and Suicide Rates: Role of Affective Disorders”, Liaugaudaite et al 2022

2022-liaugaudaite.pdf: “Association between lithium levels in drinking water and suicide rates: Role of affective disorders”⁠, Vilma Liaugaudaite, Nijole Raskauskiene, Rima Naginiene, Narseta Mickuviene, Leo Sher (2022-02-01; ; similar):

  • Lithium levels in drinking water are positively associated with the incidence of affective disorders.
  • Higher lithium levels in drinking water are inversely associated with the lower suicide rates in areas with high incidence of affective disorders.
  • Even very low levels of lithium in drinking water may play a role to save lives among people with affective disorders.

Objective: The study aimed to assess the association between lithium levels in drinking water from public supplies and suicide rates in different municipalities of Lithuania in relation with incidence of affective disorders.

Methods: 53 drinking water samples were analysed from the main public drinking water systems of the country’s municipalities. Lithium levels were determined using the ion chromatography method. Information on all registered affective disorders across all age groups and gender within the 5-year period was obtained from the Department of Statistics, and was averaged across the investigation time period. For the statistical analysis, lithium levels were averaged per municipality and plotted against suicide standardized mortality rates per 100,000 populations, within the 5-year period.

Results: We found that lithium levels in drinking water are positively associated with the incidence of affective disorders. Our findings suggest higher incidence rates of affective disorders in the municipalities with a lithium level in drinking water above median compared to those in the municipalities with a lithium level below median and with the same socio-demographic and psychiatric characteristics. Suicide mortality rates are inversely associated with lithium levels in drinking water only in municipalities with higher lithium levels (above median) and with a high rate of affective disorders.

Conclusion: Based on our study results and insights we generate the following hypothesis for the further research, that lithium level in drinking water might have an important protective effect against suicide rates in the population with affective disorders.

[Keywords: lithium, drinking water, affective disorders, suicide]

“Investigation of the Association between Lithium Levels in Drinking Water and Suicide Mortality in Hungary”, Izsak et al 2022

2022-izsak.pdf: “Investigation of the association between lithium levels in drinking water and suicide mortality in Hungary”⁠, Balint Izsak, Anna Hidvegi, Lajos Balint, Tibor Malnasi, Marta Vargha, Tamas Pandics, Zoltan Rihmer, Peter Dome et al (2022-02-01; ; backlinks; similar):

  • Lithium (Li) has been demonstrated to have antisuicidal effects in clinical doses.
  • Some studies have also demonstrated that Li is bioactive in very low doses.
  • We found that tap water Li levels are inversely associated with suicide mortality.

Background: In recent decades, a series of ecological studies from various countries have attempted to reveal whether there is an association between trace amounts of lithium in drinking water and suicide mortality. With some notable exceptions, results have indicated that there is an inverse association between these 2 variables. Since Hungary had extremely high rates of suicide with a persistent spatial pattern, we consider that our country is ideal to investigate this research question.

Methods: We carried out our research on Hungarian data at the level of districts (n = 197). The dependent variable was the age-standardized and gender-standardized mortality ratio for suicide (sSMR). Our main explanatory variable was the tap water lithium level (Li) from public drinking water supply systems using their own water source (n = 1 325). Those data, which give full national coverage, were aggregated to the level of districts. Confounding factors were religiosity, alcohol consumption and income. Various regression models were used for statistical calculations.

Results: Findings from our most appropriate regression model—adjusted for relevant confounding variables and able to handle spatial autocorrelation and heteroscedasticity—suggest a statistically-significant (p < 0.05) and a trend-like (p < 0.10) negative association between Li and sSMR in the total population and among males, respectively. However, such an association was not found between these 2 variables among females.

Conclusion: In line with the majority of findings from other countries, our results indicate that the intake of lithium with drinking water may have a gender-dependent suicide-protective effect.

[Keywords: lithium, drinking water, suicide, prevention, mortality]

“Trace Elements in Drinking Water and the Incidence of Attention-deficit Hyperactivity Disorder”, Thygesen et al 2021

2021-thygesen.pdf: “Trace elements in drinking water and the incidence of attention-deficit hyperactivity disorder”⁠, Malene Thygesen, Jörg Schullehner, Birgitte Hansen, Torben Sigsgaard, Denitza D. Voutchkova, Søren Munch Kristiansen et al (2021-12-01; ; similar):

Background: Trace elements have been suggested to have neurotoxic effects and increase the risk of neurodevelopmental disorders, but studies of a potential role of trace elements in relation to Attention-Deficit/​Hyperactivity Disorder (ADHD) are very limited. The objective of this study was to conduct an exploratory analysis investigating the associations between 17 geogenic trace elements (Ba⁠, Co⁠, Eu⁠, I⁠, Li⁠, Mo⁠, Rb⁠, Re⁠, Rh⁠, Sb⁠, Sc⁠, Se⁠, Si⁠, Sr⁠, Ti⁠, U and Y) found in Danish drinking water and the risk of developing ADHD.

Methods: In this cohort study, 284,309 individuals, born 1994–2007, were followed for incidence of ADHD from the age of 5 until the end of study, December 31, 2016. We conducted survival analyses, using Poisson regression to estimate incidence rate ratios (IRRs) with 95% confidence intervals (CI) in 3 different confounder adjustment scenarios.

Results: In a model including adjustments for age, sex, calendar year, parental socio-economic status⁠, neighborhood level socio-economic status and parental psychiatric illness, we found that 6 of the 17 trace elements (Sr, Rb, Rh, Ti, Sb and Re) were associated with an increased risk of ADHD, whereas 2 (Ba and I) were inversely associated with ADHD. However, when including region as a covariate in the model, most trace elements were no longer associated with ADHD or the association changed direction. 4 trace elements (I, Li, Rb, and Y) remained statistically-significantly associated with ADHD but in an inverse direction and for 3 of these (I, Li and Y), we found statistically-significant interactions with region in their association with ADHD.

Conclusion: The trace elements under investigation, at levels found in Danish drinking water, do not seem to contribute to the development of ADHD and our findings highlight the importance of examining consistency of associations across geographic areas.

[Keywords: trace elements, drinking water, neurodevelopment, ADHD]

“Lithium Can Mildly Increase Health during Ageing but Not Lifespan in Mice”, Nespital et al 2021

“Lithium can mildly increase health during ageing but not lifespan in mice”⁠, Tobias Nespital, Brit Neuhaus, Andrea Mesaros, André Pahl, Linda Partridge (2021-09-21; ; similar):

Lithium is a nutritional trace element, used clinically as an anti-depressant. Preclinically, lithium has neuroprotective effects in invertebrates and mice, and it can also extend lifespan in fission yeast, C. elegans and Drosophila. An inverse correlation of human mortality with the concentration of lithium in tap water suggests a possible, evolutionarily conserved mechanism mediating longevity.

Here, we assessed the effects of lithium treatment on lifespan and ageing parameters in mice. Lithium has a narrow therapeutic dose range, and overdosing can severely affect organ health.

Within the tolerable dosing range, we saw some mildly positive effects of lithium on health span but not on lifespan.

“Lithium in Groundwater Used for Drinking-water Supply in the United States”, Lindsey et al 2021

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; similar):

  • 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.

Graphical abstract: public supply groundwater wells in the USA, locations & lithium concentrations

“Lithium in Drinking Water, Altitude, and Suicide Rates in Rural Areas of Argentinean Andes”, Steinmetz et al 2021

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 et al (2021-02-01; backlinks; similar):

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]

“The Association between Lithium in Drinking Water and Neuropsychiatric Outcomes: A Systematic Review and Meta-analysis from across 2678 Regions Containing 113 Million”, Eyre-Watt et al 2020

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; backlinks; similar):

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]

“Lithium in Drinking Water and Suicide Prevention: The Largest Nationwide Epidemiological Study from Japan”, Kugimiya et al 2020

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 et al (2020-08-11; backlinks; similar):

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.

“Association between Naturally Occurring Lithium in Drinking Water and Suicide Rates: Systematic Review and Meta-analysis of Ecological Studies”, Memon et al 2020

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 et al (2020-07-27; ⁠, ; backlinks; similar):

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 (ie. 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.

“Association between Lithium in Tap Water and Suicide Mortality Rates in Miyazaki Prefecture”, Kozaka et al 2020

“Association between lithium in tap water and suicide mortality rates in Miyazaki Prefecture”⁠, Naomi Kozaka, Shouhei Takeuchi, Nobuyoshi Ishii, Takeshi Terao, Yoshiki Kuroda (2020-06-27; backlinks; similar):

Background: Most studies have reported that suicide mortality rates are negatively associated with lithium levels in tap water; however, a few studies showed either no association or a positive association. Thus, the association between suicide mortality and lithium levels in tap water remains controversial. To clarify the association, our study evaluated the association between lithium levels in tap water and suicide mortality rates in Miyazaki Prefecture of Japan, after adjusting for confounding factors.

Methods: We measured lithium levels in tap water across the 26 municipalities of Miyazaki Prefecture in Japan. We examined the standardized mortality ratio (SMR) for suicide in each municipality and used the data as the average suicide SMRs over 5 years (2009–2013). Weighted least-squares regression analysis, adjusted for the size of each municipality’s population, was used to investigate the association between lithium levels in tap water and suicide SMRs. In addition to a crude model, in an adjusted model, potential confounding factors (proportion of elderly people, proportion of one-person households, annual marriage rate, annual mean income, unemployment rate, the density of medical doctors per 100,000 people, annual total rainfall, and proportion of people with a college education or higher) were added as covariates.

Results: We showed that male and female suicide SMRs were not associated with lithium levels in tap water in Miyazaki Prefecture. After adjusting for confounders, male suicide SMRs were statistically-significantly and positively associated with the proportion of elderly people in the population and annual total rainfall, and female suicide SMRs were associated with the proportion of elderly people in the population.

Conclusions: No association between lithium levels in tap water and suicide mortality rates was found in Miyazaki Prefecture.

“Relationship between Suicide Mortality and Lithium in Drinking Water: A Systematic Review and Meta-analysis”, Barjasteh-Askari et al 2020

2020-barjastehaskari.pdf: “Relationship between suicide mortality and lithium in drinking water: A systematic review and meta-analysis”⁠, Fateme Barjasteh-Askari, Mojtaba Davoudi, Homayoun Amini, Mohammad Ghorbani, Mehdi Yaseri, Masoud Yunesian et al (2020-03-01; backlinks)

“High Lithium Levels in Tobacco May Account for Reduced Incidences of Both Parkinson’s Disease and Melanoma in Smokers through Enhanced Β-catenin-mediated Activity”, Guttuso 2019

2019-guttuso.pdf: “High lithium levels in tobacco may account for reduced incidences of both Parkinson’s disease and melanoma in smokers through enhanced β-catenin-mediated activity”⁠, Thomas Guttuso (2019-10-01)

“Inverse Relationship between Lithium Levels in Drinking Water and Suicide Rates”, Liaugaudaite et al 2019

2019-liaugaudaite.pdf: “Inverse relationship between lithium levels in drinking water and suicide rates”⁠, V. Liaugaudaite, R. Naginiene, N. Raskauskiene, N. Mickuviene, A. Bunevicius, L. Sher (2019-09-07; backlinks)

“Lithium‐Rich Mineral Water Is a Highly Bioavailable Lithium Source for Human Consumption”, Seidel et al 2019

2019-seidel.pdf: “Lithium‐Rich Mineral Water is a Highly Bioavailable Lithium Source for Human Consumption”⁠, Ulrike Seidel, Elena Baumhof, FranziskaA Hägele, Anja Bosy-Westphal, Marc Birringer, Gerald Rimbach (2019-01-01)

“Lithium in Drinking Water Associated With Adverse Mental Health Effects”, Schullehner et al 2019

2019-schullehner.pdf: “Lithium in drinking water associated with adverse mental health effects”⁠, Jörg Schullehner, Diana Paksarian, Birgitte Hansen, Malene Thygesen, Søren Munch Kristiansen, Søren Dalsgaard et al (2019-01-01; backlinks)

“Adding Lithium to Drinking Water for Suicide Prevention—The Ethics”, Ng et al 2019

2019-ng.pdf: “Adding Lithium to Drinking Water for Suicide Prevention—The Ethics”⁠, Jared Ng, Manne Sjöstrand, Nir Eyal (2019; similar):

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.

“Naturally Absorbed Polyunsaturated Fatty Acids, Lithium, and Suicide-related Behaviors: A Case-controlled Study”, Keiko et al 2018

2018-kurosawa.pdf: “Naturally absorbed polyunsaturated fatty acids, lithium, and suicide-related behaviors: A case-controlled study”⁠, Kurosawa Keiko, Terao Takeshi, Masayuki Kanehisa, Ippei Shiotsuki, Ishii Nobuyoshi, Ryuichi Takenaka et al (2018-12-01; similar):

  • Higher plasma EPA levels and higher serum lithium levels may be associated with less suicide attempt.
  • Higher plasma arachidonic acid levels may be associated with more deliberate self-harm.
  • As naturally absorbed nutrients, low arachidonic acid levels may be effective for deliberate self-harm while high EPA and high lithium levels may be effective for suicide attempts.

Objective: Previous studies have investigated the effects of omega-3⁠, omega-6 and lithium on suicide-related behaviors separately. This study was performed to comprehensively investigate the effects of naturally absorbed EPA, DHA, arachidonic acid and lithium in relation to suicide attempt and deliberate self-harm, with adjustment for each other.

Methods: We analyzed plasma EPA, DHA, arachidonic acid levels and serum lithium levels of 197 patients including 33 patients with suicide attempts, 18 patients with deliberate self-harm, and 146 control patients.

Results: Multivariate logistic regression analysis with adjustment for age, gender, EPA, DHA, arachidonic acid and log-transformed lithium levels revealed that the negative associations with EPA levels (adjusted OR 0.972, 95% CI 0.947–0.997, p = 0.031) and log-transformed lithium levels (adjusted OR 0.156, 95% CI 0.038–0.644, p = 0.01) and the positive association with DHA levels (adjusted OR 1.026, 95% CI 1.010–1.043, p = 0.002) were statistically-significant in patients with suicide attempts than in control patients. The analysis also demonstrated that the positive association with arachidonic acid levels (adjusted OR 1.015, 95% CI 1.005–1.025, p = 0.004) was statistically-significant in patients with deliberate self-harm than in control patients.

Limitations: The limitations are relatively small number of patients and the effects of demographics of individual patients could not be adjusted for the analyses.

Conclusions: The present findings suggest that, as naturally absorbed nutrients, higher EPA and lithium levels may be associated with less suicide attempt, and that higher arachidonic acid levels may be associated with more deliberate self-harm.

[Keywords: EPA, DHA, arachidonic acid, self-harm, suicide attempt]

“Association Between Groundwater Lithium and the Diagnosis of Bipolar Disorder and Dementia in the United States”, Parker et al 2018

“Association Between Groundwater Lithium and the Diagnosis of Bipolar Disorder and Dementia in the United States”⁠, William F. Parker, Rebecca J. Gorges, Y. Nina Gao, Yudong Zhang, Kwan Hur, Robert D. Gibbons (2018-07; backlinks; similar):

Groundwater lithium concentrations were collected by the US Geological Survey from more than 3000 drinking water wells from 1992 to 2003…Claims data for 4,227,556 adults living in 174 counties were analyzed, including 3,046,331 with private insurance, 261,461 with Medicare Supplemental, and 919,764 with Medicaid. Among them, 404,662 patients (9.6%) lived in 1 of 32 counties with high lithium (>40 μg/​L). The mean and median lithium concentrations were 27.4 μg/​L and 11.1 μg/​L, respectively (IQR⁠, 3.7–23.6 μg/​L).

Unadjusted prevalence rates for all outcomes were statistically-significantly lower in high-lithium counties. However, high-lithium counties had fewer physicians and health care resources and had smaller, younger, less educated, and more Hispanic populations (Table).

After adjustment for county-level demographics and health care resources, high lithium did not confer any statistically-significant benefit for bipolar disorder, dementia, or the negative controls major depressive disorder, myocardial infarction, or prostate cancer. The Figure shows the lack of any association across the entire lithium distribution.

Discussion: Despite the substantial variation in groundwater lithium exposure in the United States, we found no statistically-significant association between groundwater lithium exposure and risk of bipolar disorder or dementia after adjustment for county-level demographics and health care resource. This indicates the purported association of high-lithium concentrations in drinking water with mental health disorders is driven by unaccounted variation in demographics, health care resources, and diagnosis practices.

Therapeutic lithium doses are orders of magnitude larger than groundwater lithium concentrations, making a true causal relationship between groundwater lithium and mental health biologically dubious. In our study, the high-lithium group was exposed to a mean of 141.3 μg/​L in their water supply. This means that a patient would need to drink more than 1000 L of water a day to ingest the lowest reported effective therapeutic lithium dose of 150 mg.

“Lithium in Drinking Water and Food, and Risk of Suicide”, Chandra & Babu 2018

“Lithium in drinking water and food, and risk of suicide”⁠, Prabha S. Chandra, Girish N. Babu (2018-01-02; backlinks; similar):

The study by Ohgami et al raises serious ethical issues related to the interpretation of research findings and, as a consequence, their possible application. While not denying that the findings are interesting and have caused a stir in the lay press and on the internet, we question the methodology and the possible implications if the results are taken seriously.

First, sociological reasons for suicide are important, and changing rates of suicide in many countries are linked to changes such as migration, poverty, relationships and economic issues. The finding that when gender was included in the analysis there was a difference in the statistical-significance levels between men and women (with the results being less statistically-significant in women) is one such example. Adding lithium to tap water is not going to change these demographic and social factors that contribute to suicide rates, and not having accounted for at least some of these is a major limitation of the study. Second, although we agree with Young in his commentary that more research is needed to prove or disprove this tantalizing idea, it is also important to assess what the impact of different levels of tap-water lithium is going to be on thyroid function, pregnant women and on the unborn fetus. It is also important to assess whether tap-water levels of lithium directly correlate with serum lithium levels in the respective populations. The levels of lithium in body fluids in normal healthy controls have varied from 0.01 to 0.09 meq/​1 in one study, but there are no data about serum lithium levels among individuals attempting suicide. Maybe assessment of serum lithium levels among those with suicidal behaviour can be a place to start. More data are also needed on the role of low-dose lithium in individuals without mood disorders who are at risk of suicide.

Finally, several foods (particularly spices) are known to have relatively high levels of lithium as reported by a study in India several years ago. This study reported levels as high as 12 μg/​g of lithium in tobacco and high levels in crude salt, rock salt and several spices. Maybe, until such time that we are certain about lithium’s role in decreasing suicidality in non-psychiatric populations, it might be worth conducting randomised controlled trials with these foods in individuals with suicidal behaviour to see whether low doses of lithium really help.

Let us not throw the lithium out with the tap water yet!

“Lithium Levels in Tap Water and Psychotic Experiences in a General Population of Adolescents”, Shimodera et al 2018

2018-shimodera.pdf: “Lithium levels in tap water and psychotic experiences in a general population of adolescents”⁠, Shinji Shimodera, Shinsuke Koike, Shuntaro Ando, Syudo Yamasaki, Ryosuke Fujito, Kaori Endo, Yudai Iijima et al (2018-01-01; backlinks)

“Psychiatric Benefits of Lithium in Water Supplies May Be due to Protection from the Neurotoxicity of Lead Exposure”, Brown et al 2018

2018-brown.pdf: “Psychiatric benefits of lithium in water supplies may be due to protection from the neurotoxicity of lead exposure”⁠, Eric E. Brown, Philip Gerretsen, Bruce Pollock, Ariel Graff-Guerrero (2018-01-01)

“The Association Between Lithium in Drinking Water and Incidence of Suicide Across 15 Alabama Counties”, Palmer et al 2018

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; backlinks; similar):

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.

“Trace Lithium in Texas Tap Water Is Negatively Associated With All-cause Mortality and Premature Death”, Fajardo et al 2018

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; backlinks; similar):

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.

“Lithium Levels in the Public Drinking Water Supply and Risk of Suicide: A Pilot Study”, Liaugaudaite et al 2017

2017-liaugaudaite.pdf: “Lithium levels in the public drinking water supply and risk of suicide: A pilot study”⁠, Vilma Liaugaudaite, Narseta Mickuviene, Nijole Raskauskiene, Rima Naginiene, Leo Sher (2017-09-01; backlinks; similar):

  • The suicide-protective property of natural lithium was confirmed with a positive effect for men.
  • Higher lithium levels in drinking water might have a protective effect on the risk of suicide in men.
  • Evaluation of lithium in a local drinking water, might provide regional effective prevention programs.

Suicide is a major public health concern affecting both the society and family life. There are data indicating that higher level lithium intake with drinking water is associated with lower suicide rate. This pilot study examined the relationship between lithium levels in drinking water and suicide rates in Lithuania.

22 samples from public drinking water systems were taken in 9 cities of Lithuania. The lithium concentration in these samples was determined by inductively coupled plasma mass spectrometry (ICP-MS). The suicide data were obtained from the Lithuania Database of Health Indicators, and comprised all registered suicides across all ages and gender within the 5-year period from 2009 to 2013.

The study demonstrated an inverse correlation between levels of lithium (log natural transformed), number of women for 1000 men and standardized mortality rate for suicide among total study population. After adjusting for confounder (the number of women for 1000 men), the lithium level remained statistically-significant in men, but not in women.

Our study suggested that higher levels of lithium in public drinking water are associated with lower suicide rates in men. It might have a protective effect on the risk of suicide in men.

“Lithium in Drinking Water and Incidence of Suicide: A Nationwide Individual-Level Cohort Study With 22 Years of Follow-Up”, Knudsen et al 2017

“Lithium in Drinking Water and Incidence of Suicide: A Nationwide Individual-Level Cohort Study with 22 Years of Follow-Up”⁠, Nikoline N. Knudsen, Jörg Schullehner, Birgitte Hansen, Lisbeth F. Jørgensen, Søren M. Kristiansen, Denitza D. Voutchkova et al (2017-06-10; backlinks; similar):

Suicide is a major public health concern. High-dose lithium is used to stabilize mood and prevent suicide in patients with affective disorders. Lithium occurs naturally in drinking water worldwide in much lower doses, but with large geographical variation. Several studies conducted at an aggregate level have suggested an association between lithium in drinking water and a reduced risk of suicide; however, a causal relation is uncertain.

Individual-level register-based data on the entire Danish adult population (3.7 million individuals) from 1991 to 2012 were linked with a moving 5-year time-weighted average (TWA) lithium exposure level from drinking water hypothesizing an inverse relationship. The mean lithium level was 11.6 μg/​L ranging from 0.6 to 30.7 μg/​L. The suicide rate decreased from 29.7 per 100,000 person-years at risk in 1991 to 18.4 per 100,000 person-years in 2012.

We found no statistically-significant indication of an association between increasing 5-year TWA lithium exposure level and decreasing suicide rate. The comprehensiveness of using individual-level data and spatial analyses with 22 years of follow-up makes a pronounced contribution to previous findings.

Our findings demonstrate that there does not seem to be a protective effect of exposure to lithium on the incidence of suicide with levels below 31 μg/​L in drinking water.

[Keywords: drinking water, lithium, suicide, individual-level data, spatial analysis, Denmark, exposure assessment]

“Re-analysis of the Association of Temperature or Sunshine With Hyperthymic Temperament Using Lithium Levels of Drinking Water”, Matsuzaki et al 2017

2017-matsuzaki.pdf: “Re-analysis of the association of temperature or sunshine with hyperthymic temperament using lithium levels of drinking water”⁠, Hideki Matsuzaki, Takeshi Terao, Takeshi Inoue, Yoshikazu Takaesu, Nobuyoshi Ishii, Kentaro Kohno, Minoru Takeshima et al (2017-01-01; backlinks)

“Trace Lithium and Mental Health”, Ishii & Terao 2017

2017-ishii.pdf: “Trace lithium and mental health”⁠, Nobuyoshi Ishii, Takeshi Terao (2017-01-01)

“Trace Lithium Is Inversely Associated With Male Suicide After Adjustment of Climatic Factors”, Shiotsuki et al 2016

2016-shiotsuki.pdf: “Trace lithium is inversely associated with male suicide after adjustment of climatic factors”⁠, Ippei Shiotsuki, Takeshi Terao, Nobuyoshi Ishii, Shouhei Takeuchi, Yoshiki Kuroda, Kentaro Kohno, Yoshinori Mizokami et al (2016-01-01; backlinks)

“IWBP_A_1062551.indd”, Pompili et al 2015

2015-pompili.pdf: “IWBP_A_1062551.indd”⁠, Maurizio Pompili, Monica Vichi, Enrico Dinelli, Roger Pycha, Paolo Valera, Stefano Albanese, Annamaria Lima et al (2015-01-01; backlinks)

“Standard and Trace-dose Lithium: A Systematic Review of Dementia Prevention and Other Behavioral Benefits”, Mauer et al 2014

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; ; backlinks; similar):

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]

“Technology Forecasting: The Garden of Forking Paths”, Branwen 2014

Forking-Paths: “Technology Forecasting: The Garden of Forking Paths”⁠, Gwern Branwen (2014-06-01; ⁠, ⁠, ⁠, ; backlinks; similar):

Pessimistic forecasters are overconfident in fixating, hedgehog-like, on only one scenario for how they think something must happen; in reality, there are always many ways through the garden of forking paths, and something needs only one path to happen.

A classic cognitive bias in technological forecasting is motivated-stopping and lack of imagination in considering possibilities for a steelman⁠.

Many people use a mental model of technologies in which they proceed in a serial sequential fashion and assume every step is necessary and only all together are they sufficient, and note that some particular step is difficult or unlikely to succeed and thus as a whole it will fail & never happen. But in reality, few steps are truly required.

Progress is predictably unpredictable: A technology only needs to succeed in one way to succeed, and to fail it must fail in all ways. There may be many ways to work around, approximate, brute force, reduce the need for, or skip entirely a step, or redefine the problem to no longer involve that step at all. Examples of this include the parallel projects used by the Manhattan Project & Apollo program, which reasoned that despite the formidable difficulties in each path to the end goal, at least one would work out—and they did.

In forecasting, to counter this bias, one should make a strong effort to imagine all possible alternatives which could be pursued in parallel, and remember that overall failure requires all of them to fail.

“Does Altitude Moderate the Impact of Lithium on Suicide? A Spatial Analysis of Austria”, Helbich et al 2013

2013-helbich.pdf: “Does altitude moderate the impact of lithium on suicide? A spatial analysis of Austria”⁠, Marco Helbich, Victor Blüml, Michael Leitner, Nestor D. Kapusta (2013-05-01; backlinks; similar):

Suicide, the tenth leading cause of death worldwide, is a complex phenomenon. Models aiming to explain the interaction of ambient variables such as socioeconomic factors, lithium content of drinking water and altitude are poorly developed.

While controlling for several risk factors, this research bridges 2 different, but complementary research lines by investigating statistically the relationship on suicide mortality between lithium levels in drinking water in response to altitude above sea level. Besides regression models with main effects, a multiplicative interaction model between lithium and altitude has been developed providing estimates at the district-level for Austria where spatial autocorrelation was accounted for through spatial filtering.

The correlation results showed a negative association between lithium levels and altitude. The regression confirmed a negative association of lithium levels and suicide mortality. Altitude was found to be positively associated with suicide mortality. On the other hand, lithium effects on suicide mortality were found to be moderated by altitude. In lower altitude regions the effect turned out to be negatively related to suicide mortality, while lithium had a positive association in high-altitude regions.

These results provide evidence for the fact that the relationship between lithium, altitude and suicide rates is more complex than hitherto assumed. Further research on the effects of ambient variables such as low levels of lithium on suicide is needed and particularly the lithium-altitude interaction is worth further investigation to understand possible underlying neurochemical processes.

“Lithium in the Public Water Supply and Suicide Mortality in Texas”, Blüml et al 2013

2013-bluml.pdf: “Lithium in the public water supply and suicide mortality in Texas”⁠, Victor Blüml, Michael D. Regier, Gerald Hlavin, Ian R. H. Rockett, Franz König, Benjamin Vyssoki, Tom Bschor et al (2013-01-01; backlinks)

“Iodine and Adult IQ Meta-analysis”, Branwen 2012

Iodine: “Iodine and Adult IQ meta-analysis”⁠, Gwern Branwen (2012-02-29; ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

Iodine improves IQ in fetuses; adults as well? A meta-analysis of relevant studies says no.

Iodization is one of the great success stories of public health intervention: iodizing salt costs pennies per ton, but as demonstrated in randomized & natural experiments, prevents goiters, cretinism, and can boost population IQs by a fraction of a standard deviation in the most iodine-deficient populations.

These experiments are typically done on pregnant women, and results suggest that the benefits of iodization diminish throughout the trimesters of a pregnancy. So does iodization benefit normal healthy adults, potentially even ones in relatively iodine-sufficient Western countries?

Compiling existing post-natal iodization studies which use cognitive tests, I find that—outliers aside—the benefit appears to be nearly zero, and so likely it does not help normal healthy adults, particularly in Western adults.

“The Replication Crisis: Flaws in Mainstream Science”, Branwen 2010

Replication: “The Replication Crisis: Flaws in Mainstream Science”⁠, Gwern Branwen (2010-10-27; ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

2013 discussion of how systemic biases in science, particularly medicine and psychology, have resulted in a research literature filled with false positives and exaggerated effects, called ‘the Replication Crisis’.

Long-standing problems in standard scientific methodology have exploded as the “Replication Crisis”: the discovery that many results in fields as diverse as psychology, economics, medicine, biology, and sociology are in fact false or quantitatively highly inaccurately measured. I cover here a handful of the issues and publications on this large, important, and rapidly developing topic up to about 2013, at which point the Replication Crisis became too large a topic to cover more than cursorily. (A compilation of some additional links are provided for post-2013 developments.)

The crisis is caused by methods & publishing procedures which interpret random noise as important results, far too small datasets, selective analysis by an analyst trying to reach expected/​desired results, publication bias, poor implementation of existing best-practices, nontrivial levels of research fraud, software errors, philosophical beliefs among researchers that false positives are acceptable, neglect of known confounding like genetics, and skewed incentives (financial & professional) to publish ‘hot’ results.

Thus, any individual piece of research typically establishes little. Scientific validation comes not from small p-values, but from discovering a regular feature of the world which disinterested third parties can discover with straightforward research done independently on new data with new procedures—replication.

“The Cost of Crime to Society: New Crime-specific Estimates for Policy and Program Evaluation”, McCollister et al 2010

“The cost of crime to society: new crime-specific estimates for policy and program evaluation”⁠, Kathryn E. McCollister, Michael T. French, Hai Fang (2010; ⁠, ; backlinks; similar):

Estimating the cost to society of individual crimes is essential to the economic evaluation of many social programs, such as substance abuse treatment and community policing. A review of the crime-costing literature reveals multiple sources, including published articles and government reports, which collectively represent the alternative approaches for estimating the economic losses associated with criminal activity. Many of these sources are based upon data that are more than 10 years old, indicating a need for updated figures.

This study presents a comprehensive methodology for calculating the cost to society of various criminal acts. Tangible and intangible losses are estimated using the most current data available. The selected approach, which incorporates both the cost-of-illness and the jury compensation methods, yields cost estimates for more than a dozen major crime categories, including several categories not found in previous studies. Updated crime cost estimates can help government agencies and other organizations execute more prudent policy evaluations, particularly benefit-cost analyses of substance abuse treatment or other interventions that reduce crime.

“Lithium Levels in Drinking Water and Risk of Suicide”, Ohgami et al 2009

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; backlinks; similar):

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.

“Even Very Low but Sustained Lithium Intake Can Prevent Suicide in the General Population?”, Terao et al 2009

2009-terao.pdf: “Even very low but sustained lithium intake can prevent suicide in the general population?”⁠, Takeshi Terao, Shinjiro Goto, Masatoshi Inagaki, Yasumasa Okamoto (2009-01-01; backlinks)

“Drinking Spring Water and Lithium Absorption: A Preliminary Study”, Shiotsuki et al 2008

2008-shiotsuki.pdf: “Drinking Spring Water and Lithium Absorption: A Preliminary Study”⁠, Ippei Shiotsuki, Takeshi Terao, Hirochika Ogami, Nobuyoshi Ishii, Reiji Yoshimura, Jun Nakamura (2008-11-14; backlinks; similar):

Background: In Japan, there are several resorts with cold springs that have mineral water containing relatively high levels of lithium compared to tap water. Visitors to such cold-spring resorts traditionally drink 2 to 4 L of mineral water for several hours in the early morning in the belief that the water has properties which maintain physical health. The present study aimed to investigate whether drinking the water increase serum lithium levels despite frequent urination, and to examine the mental effects of drinking mineral water containing lithium and related factors.

Methods: 43 subjects who were not psychiatrically ill gave informed consent to this study. Before and just after drinking the water, serum lithium levels, the State-Trait of Anxiety Inventory (STAI) scores, Profiles of Mood States Test (POMS) scores and brain-derived neurotrophic factor (BDNF) levels were measured.

Results: The subjects drank 3.64 L of the water in the early morning. Serum lithium levels were statistically-significantly increased from 0.026 to 0.073 mEq/​L, which were much lower than the ones used in the treatment of psychiatric disorders. After drinking, most ratings of POMS statistically-significantly improved. Serum lithium levels were positively and statistically-significantly associated with serum BDNF levels, and changes in serum BDNF were negatively and statistically-significantly associated with changes in STAI state scores.

Conclusion: The present findings suggest that drinking mineral water containing very low lithium levels may increase serum lithium levels and improve mental state as a likely consequence of changes in BDNF levels, although improvement in subjective well-being may have been due to placebo effect. Taking several methodological limitations into consideration, further studies are required to confirm this suggestion.

[Keywords: lithium, mineral water, cold spring, STAI, POMS, BDNF]

“Lithium May Be Useful in the Prevention of Alzheimer’s Disease in Individuals at Risk of Presenile Familial Alzheimer’s Disease”, Yeh & Tsai 2008

2008-yeh.pdf: “Lithium may be useful in the prevention of Alzheimer’s disease in individuals at risk of presenile familial Alzheimer’s disease”⁠, Heng-Liang Yeh, Shih-Jen Tsai (2008-01-01; backlinks)

“Lithium Treatment Reduces Suicide Risk in Recurrent Major Depressive Disorder”, Guzzetta & al 2007

2007-guzzetta.pdf: “Lithium Treatment Reduces Suicide Risk in Recurrent Major Depressive Disorder”⁠, Guzzetta, et al (2007-01-01; backlinks)

“Lithium in the Prevention of Suicidal Behavior and All-Cause Mortality in Patients With Mood Disorders: A Systematic Review of Randomized Trials”, Cipriani et al 2005

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; backlinks; similar):

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.

Miscellaneous