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Lithium - Pharmaceutical

  • Drugs
  • Updated April 23, 2024

Lithium is a naturally occurring element that can affect cell signaling in the brain. The medication can help treat psychiatric disorders, but patients must be carefully monitored because serious side effects can occur. Some studies suggest that a low pharmaceutical dose of lithium may provide some cognitive benefit to patients with mild cognitive impairment or dementia, but findings are inconsistent. Ongoing studies may shed new light on the use of lithium for cognitive health and dementia. The safety of even low doses of lithium for elderly people is uncertain.

Evidence

No clinical trials have studied whether lithium prevents cognitive decline in healthy older adults. Some observational studies have examined the relationship between lithium intake and incidence of dementia. Our search identified:

  • 2 systematic reviews and meta-analyses 
  • 11 clinical trials (2 in people with mild cognitive impairment, 4 in Alzheimer's patients, 5 in amyotrophic lateral sclerosis [ALS] patients)
  • 9 observational studies
  • Numerous preclinical studies

Potential Benefit

The clinical trials that have evaluated lithium treatment for mild cognitive impairment have reported mixed results; some, particularly longer-term studies, found benefits of lithium treatment such as disease stabilization [1]. While this study tested lithium over years and compared to a placebo, the people in the placebo group were older than the people in the lithium treatment group, making it difficult to say whether the lithium treatment helped or whether the older patients were declining more quickly. 

Long-term pharmaceutical use of lithium has been associated with a lower risk of dementia in several observational studies [2; 3; 4] and reduced rates of brain aging [5] for bipolar patients, though this pattern has not been seen in all studies [6]. Additionally, some studies have found that geographically varying levels of lithium in groundwater may be associated with dementia incidence [7], though other studies have not replicated these results [8], and geographic location can introduce many other factors that can influence risk of dementia. 

Preclinical studies suggest several ways lithium can improve brain health, including increasing stem cell activity, accelerating the absorption of vitamin B12 and folate, and increasing the elimination of aggregated proteins such as beta-amyloid that are associated with Alzheimer's and other brain disorders [9; 10]. Most of these mechanisms, however, have not been validated in humans and lithium has not yet lived up to its promise as an effective treatment for ALS [11; 12]

For Dementia Patients

Several small clinical trials of lithium treatment for dementia have been conducted. Some trials have reported disease stabilization [13] whereas some trials find no benefit [14; 15]. The trial that reported benefit was larger and longer than the trials that reported no benefit. Safety concerns and the conflicting evidence on brain health warrant more research. 

Safety

At doses that are too high, lithium can cause toxicity and severe long-term side effects, including kidney damage, especially if not treated appropriately. Safety risks are generally higher at higher doses, but the dosage risk varies by individual. Elderly people must be careful with lithium, particularly if they use multiple medications or have other health risks and diseases that interact with lithium. Safety risks are particularly high for people with kidney or cardiovascular disease, dehydration, or sodium depletion, or for people taking diuretics or haloperidol. Common drugs such as over-the-counter anti-inflammatory medications, caffeine, theophylline, antidepressants, and anti-hypertensive medications can interact with lithium [16; 17; 18]. 

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

How to Use

Lithium is usually prescribed as lithium carbonate in the form of capsules, solutions, syrups, tablets, or extended-release tablets. Dosage must be tailored on an individual basis (depending on age and drug formulation). Typically, the lowest possible dose is prescribed and then adjusted to achieve a certain range of lithium levels in the blood serum, while carefully monitoring for side effects. 

Learn More

Full scientific report (PDF) on Cognitive Vitality Reports

Dietary Lithium rating on Cognitive Vitality Reports

Check for drug-drug and drug-supplement interactions on Drugs.com

References

  1. Forlenza OV, Radanovic M, Talib LL et al. (2019) Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: randomised clinical trial. Br J Psychiatry 215, 668-674.
  2. Nunes PV, Forlenza OV, Gattaz WF (2007) Lithium and risk for Alzheimer's disease in elderly patients with bipolar disorder. Br J Psychiatry 190, 359-360.
  3. Kessing LV, Forman JL, Andersen PK (2010) Does lithium protect against dementia? Bipolar Disord 12, 87-94.
  4. Gerhard T, Devanand DP, Huang C et al. (2015) Lithium treatment and risk for dementia in adults with bipolar disorder: population-based cohort study. Br J Psychiatry 207, 46-51.
  5. Sajatovic M, Forester BP, Gildengers A et al. (2013) Aging changes and medical complexity in late-life bipolar disorder: emerging research findings that may help advance care. Neuropsychiatry (London) 3, 621-633.
  6. Dunn N, Holmes C, Mullee M (2005) Does lithium therapy protect against the onset of dementia? Alzheimer Dis Assoc Disord 19, 20-22.
  7. Kessing LV, Gerds TA, Knudsen NN et al. (2017) Association of Lithium in Drinking Water With the Incidence of Dementia. JAMA Psychiatry 74, 1005-1010.
  8. Parker WF, Gorges RJ, Gao YN et al. (2018) Association Between Groundwater Lithium and the Diagnosis of Bipolar Disorder and Dementia in the United States. JAMA Psychiatry 75, 751-754.
  9. Fornai F, Longone P, Ferrucci M et al. (2008) Autophagy and amyotrophic lateral sclerosis: The multiple roles of lithium. Autophagy 4, 527-530.
  10. Sarkar S, Rubinsztein DC (2006) Inositol and IP3 levels regulate autophagy: biology and therapeutic speculations. Autophagy 2, 132-134.
  11. Group UK-LS, Morrison KE, Dhariwal S et al. (2013) Lithium in patients with amyotrophic lateral sclerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol 12, 339-345.
  12. Gamez J, Salvado M, Martinez de la Ossa A et al. (2016) Lithium for treatment of amyotrophic lateral sclerosis: much ado about nothing. Neurologia 31, 550-561.
  13. Nunes MA, Viel TA, Buck HS (2013) Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer's disease. Curr Alzheimer Res 10, 104-107.
  14. Macdonald A, Briggs K, Poppe M et al. (2008) A feasibility and tolerability study of lithium in Alzheimer's disease. Int J Geriatr Psychiatry 23, 704-711.
  15. Hampel H, Ewers M, Burger K et al. (2009) Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study. J Clin Psychiatry 70, 922-931.
  16. Grandjean EM, Aubry JM (2009) Lithium: updated human knowledge using an evidence-based approach: part III: clinical safety. CNS Drugs 23, 397-418.
  17. D'Souza R, Rajji TK, Mulsant BH et al. (2011) Use of lithium in the treatment of bipolar disorder in late-life. Curr Psychiatry Rep 13, 488-492.
  18. McKnight RF, Adida M, Budge K et al. (2012) Lithium toxicity profile: a systematic review and meta-analysis. Lancet 379, 721-728.