Naturally occurring low-dose lithium in drinking water.

R a series of ecological studies1–7 on antisuicidal properties of naturally occurring lithium contents in drinking water have sparked interest among researchers. In this issue, Ishii and colleagues8 present further argument for the hypothesis that even low lithium doses—or rather, doses of lithium at a supplemental level—might have their place in suicide prevention. With limitations, there is some evidence from randomized controlled trials (RCTs) supporting lithium in therapeutic doses as a suicide preventative in individuals with unipolar depression, bipolar disorder, schizoaffective disorder, dysthymia, or rapid cycling. Although based on secondary analyses of spontaneous reports of suicidal behavior and completed suicide rather than systematic assessment of suicidality during RCTs, recent meta-analyses by Cipriani et al9,10 and Baldessarini et al11 suggest that the risk reduction of suicide might be as high as 60%–80%. These RCTs included measures of plasma lithium levels between 0.6–1.1 mmol/L, which corresponds to recommended doses of 600–1,200 mg/d lithium carbonate by mouth.9,10 However, the estimates of risk reduction by lithium have been criticized as too optimistic, and the first prospective RCTs of lithium versus valproate in bipolar disorder showed no difference in suicide events or attempts between both compounds,12 which share a common mode of action on glycogen synthase kinase-3β (GSK-3β), brain-derived neurotrophic factor (BDNF), and other neurobiological markers.13 Besides the general question about lithium’s antisuicidal properties, the important point with ecological studies like the one presented by Ishii and colleagues8 is that natural lithium contents of tap water range up to 1 mg or more of dissolved lithium per liter per day (1 L of water with 1 mg/L lithium per day corresponds to 6.9 mg lithium carbonate per day), depending on the geographic origin of the drinking water.2,14 Under the assumption that individuals drink not more than 2 L water per day (corresponding to a daily dose of 13.8 mg lithium carbonate by mouth), such an intake would result in a daily dose of approximately 1% of a therapeutic lithium dose. However, Ishii and colleagues8 report even much lower doses of up to 130 μg/L lithium drinking water, but they are in the range found in previous ecological studies from Japan, eg, 59 μg/L in Oita1 or even only 12.0 μg/L in Aomori prefecture.6 From a clinical perspective, preventing suicides