Updated: Aug 8
We know that higher lithium concentrations in community water supplies are associated with lower suicide rates (Eyre-Watt et al, 2020).
What about micro-lithium levels in individuals who die of suicide versus non-suicide fatalities? Lithium has existed since the beginning of time, so surely someone has attempted to answer this question.
In my new role as Assistant Professor of Clinical Psychiatry at University of Missouri-Columbia, I am exploring potential research projects, several involving low-dose lithium. While reviewing the literature, we identified an interesting study involving lithium levels in the eyes of deceased individuals.
In Tokyo, Ando et al (2022) compared body lithium levels between suicide and non-suicide fatalities as measured in aqueous humor. This was a small study including 12 suicides and 16 non-suicides.
The aqueous humor lithium concentration was significantly lower in suicides (mean 0.50 μg/L) than in non-suicides (0.92 μg/L). The authors concluded that lower lithium concentration was associated with suicide with large effect size.
Some of these suicides may have been preventable with low dose lithium supplementation. Considering other neuropsychiatric health benefits of lithium, should we be recommending lithium supplements to our patients?
Lithium orotate is available as an over-the-counter supplement.
Microdose lithium orotate pills are available on Amazon as 5, 10, and 20 mg equivalents. 130 mg of lithium orotate is equivalent to 5 mg of elemental lithium.
Usual dosing for prescription bipolar maintenance is around 900 –1,200 mg of lithium carbonate or lithium citrate.
The lowest strength prescription pill is 150 mg lithium carbonate (Eskalith) capsule. 60 mg of daily lithium can be accomplished with prescription lithium citrate liquid, which is 300 mg (equivalent) per 5 mL. So, 1 mL of liquid would be 60 mg daily. A 500 mL bottle would last for over a year. Less precise tiny doses could be accomplished by chopping 300 mg lithium carbonate tablets into tiny pieces.
I often prescribe 150 mg lithium citrate caps for general brain health (neuroprotection). There is not a specific evidence base for this particular dose. My rationale is why not use the highest convenient dose that is safe, does not require lithium level monitoring, is unlikely to cause side effects, and is cheaper than OTC lithium orotate. With the 150 mg dosage, lithium levels are usually below the threshold for detection by standard lab tests. However, TSH monitoring is necessary because we do not know the threshold for lithium-induced hypothyroidism.
The only study I could identify using 150 mg lithium specifically was a retrospective observational analysis by Sudhir Gadh who prescribed lithium 150 mg to essentially everyone who agreed to take it at a residential addiction treatment center. 2/3 of individuals in the program consented. Lithium was given as a substitute for or supplement to antidepressants and anxiolytics. "The logic being that if standard dosing of lithium is so effective at reducing imminently suicidal behavior, then perhaps low-dose lithium could be useful in reducing the 'slow-motion suicide' of addiction manifested in self-sabotage and self-harm."
Dr Gadh found that with lithium, the average buprenorphine dose was reduced by 50%, benzodiazepine usage reduced by 99%*, atypical antipsychotics down by 70%, polypharmacy lowered by 79%, and smoking cessation participation increased by 300%. Within the clinic, average census increased by 10%, retention of patients improved by 25%, employment rate and readiness both doubled. Overall program completion improved by 20% while the completion rate of those who took low-dose lithium improved by almost 100%. There were no significant changes in standard lab measurements indicating safety of low-dose lithium usage.
* The study was confounded by the comparison group consisting of patients at the treatment center prior to Dr Gadh's arrival as medical director, which brought an array of changes including deprescribing benzodiazepines. So the study does not tell us much, other than patients did better under Dr Gadh's directorship compared to his predecessor.
Dr Jim Phelps also prescribes lithium 150 mg to delay dementia , as featured in the September 2022 Carlat Psychiatry Report.
Links to full-text articles
Eyre-Watt B, Mahendran E, Suetani S, Firth J, Kisely S, Siskind D. The association between lithium in drinking water and neuropsychiatric outcomes: A systematic review and meta-analysis from across 2678 regions containing 113 million people. Aust N Z J Psychiatry. 2021 Feb;55(2):139-152. doi: 10.1177/0004867420963740. Epub 2020 Oct 13. PMID: 33045847.
Strawbridge R, Kerr-Gaffney J, Bessa G, Loschi G, Freitas HLO, Pires H, Cousins DA, Juruena MF, Young AH. Identifying the neuropsychiatric health effects of low-dose lithium interventions: A systematic review. Neurosci Biobehav Rev. 2023 Jan;144:104975. doi: 10.1016/j.neubiorev.2022.104975. Epub 2022 Nov 24. PMID: 36436738.