Comment to the letter to the editor entitled “Lithium in drinking water and suicide risk” by Tomoyuki Kawada

Luca, Antonina; Luca, Maria Luisa De

doi:10.17179/excli2022-5227

Cited by 1 publication

(1 citation statement)

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“…Early enthusiasm for the evidence of potential benefits surrounding lithium in drinking water exposure has led some to ponder the possibility of supplementing lithium as a public health measure in areas with low lithium concentrations. However, the currently unaddressed gaps in our knowledge of lithium in drinking water effects on suicide and psychiatric hospitalisation (where no dose-relationship has been established) (Eyre-Watt et al 2021 ), the unclear effects related to prenatal exposure (Harari et al 2015 ; Liew et al 2023 ), the non-linear association between lithium in drinking water concentrations and dementia risk and the inconsistency of results when sex stratification is considered (Duthie et al 2023 ), suggest caution in the interpretation of current data (Luca and Luca 2022 ). Indeed, the ongoing debate surrounding prenatal exposure to fluorinated water and lower IQ (Green et al 2019 ) should represent a cautionary tale, further underscoring how even well-consolidated practices in public health may require continuos scrutiny to better grasp their impact on the general public especially in a lifespan perspective.…”

Section: Methodsmentioning

confidence: 99%

Lithium and its effects: does dose matter?

Manchia,

Paribello,

Pinna

et al. 2024

Int J Bipolar Disord

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Background Decades of clinical research have demonstrated the efficacy of lithium in treating acute episodes (both manic and depressive), as well as in preventing recurrences of bipolar disorder (BD). Specific to lithium is its antisuicidal effect, which appears to extend beyond its mood-stabilizing properties. Lithium’s clinical effectiveness is, to some extent, counterbalanced by its safety and tolerability profile. Indeed, monitoring of lithium levels is required by its narrow therapeutic index. There is consensus that adequate serum levels should be above 0.6 mEq/L to achieve clinical effectiveness. However, few data support the choice of this threshold, and increasing evidence suggests that lithium might have clinical and molecular effects at much lower concentrations. Content This narrative review is aimed at: (1) reviewing and critically interpreting the clinical evidence supporting the use of the 0.6 mEq/L threshold, (2) reporting a narrative synthesis of the evidence supporting the notion that lithium might be effective in much lower doses. Among these are epidemiological studies of lithium in water, evidence on the antisuicidal, anti-aggressive, and neuroprotective effects, including efficacy in preventing cognitive impairment progression, Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS), of lithium; and (3) revieweing biological data supporting clinically viable uses of lithium at low levels with the delineation of a mechanistic hypothesis surrounding its purported mechanism of action. The study selection was based on the authors’ preference, reflecting the varied and extensive expertise on the review subject, further enriched with an extensive pearl-growing strategy for relevant reviews and book sections. Conclusions Clinical and molecular effects of lithium are numerous, and its effects also appear to have a certain degree of specificity related to the dose administered. In sum, the clinical effects of lithium are maximal for mood stabilisation at concentrations higher than 0.6 mEq/l. However, lower levels may be sufficient for preventing depressive recurrences in older populations of patients, and microdoses could be effective in decreasing suicide risk, especially in patients with BD. Conversely, lithium’s ability to counteract cognitive decline appears to be exerted at subtherapeutic doses, possibly corresponding to its molecular neuroprotective effects. Indeed, lithium may reduce inflammation and induce neuroprotection even at doses several folds lower than those commonly used in clinical settings. Nevertheless, findings surrounding its purported mechanism of action are missing, and more research is needed to investigate the molecular targets of low-dose lithium adequately.

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