Lithium in Drinking Water and Incidence of Suicide: A Nationwide Individual-Level Cohort Study with 22 Years of Follow-Up

Abstract

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 five-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 significant indication of an association between increasing five-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.

Antisuicidal Effects in Mood Disorders: Are They Unique to Lithium?

“…Despite [55,68]. Knudsen et al [63] found no association of exposure to lithium in drinking water in Denmark and risk of suicide in bipolar disorder.…”

“…Finally, for lithium, we carried out a systematic search and summarized findings of a growing number of studies that evaluated associations of the low concentrations of lithium in local drinking water with reported suicide or homicide rates in the same communities or regions. We found 18 such reports [53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70]. Several of these reports involved an apparently single set of data from Austria, and their findings are pooled [57][58][59]62].…”

“…Most of the studies (12/15) found a significant, inverse association between local lithium levels and local rates of suicide or homicide, though sometimes (inconsistently) only in men or women or seemingly modified by local climatic conditions or altitude. One notable study involving a national Danish sample found no such association when individual people were considered rather than relying on group (ecological) associations [63]. Two studies found a protective relationship with ▶Table 1 Risk of suicides or attempts with versus without long-term lithium treatment.…”

Is Lithium a Micronutrient? From Biological Activity and Epidemiological Observation to Food Fortification

“…Li is a naturally occurring element in surface waters, mainly in its ionic form [ 54 ]. Its concentrations, depending primarily on the processes of weathering of mineral rocks [ 19 , 55 ], differ depending on geographical region [ 23 , 56 ] and are clearly correlated with its natural resources in a certain region [ 10 ]. The available literature does not provide data on the variability of Li concentrations in water depending on time; however, taking into account its chemical properties in aqueous solutions, it can be considered as a relatively constant value.…”

“…Concentrations reaching approximately 200 μg/L were found in drinking water in selected regions of the USA (Texas), Greece, Japan, England, and Italy [ 63 – 65 ]. In comparison with the medicinal doses of 600–2400 mg Li 2 CO 3 /day (113–452 mg Li/day), concentrations occurring in surface and underground waters are very low [ 55 , 66 , 67 ]. Even though the concentrations of Li in some regions of the world reach as much as 5.2 mg/L [ 68 ], in tap water in Europe, they generally reach several dozen micrograms per liter [ 13 , 68 ].…”