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Lithium - Pharmaceutical

  • Drugs
  • Updated September 21, 2016

Lithium is a highly reactive and light metal that can affect cell signaling in the brain. High doses can help treat mania and depression, but must be carefully monitored because serious side effects can occur. High doses are unlikely to help Alzheimer's patients, but a low pharmaceutical dose may improve cognition and protect against Alzheimer's in elderly people with mild memory impairment. The safety of even low doses of lithium for elderly people is uncertain.

Evidence

There are no clinical trials or observational studies testing lithium’s ability to protect from cognitive decline or dementia in healthy older adults. Our search identified:

• 0 meta-analyses
• 8 randomized controlled trials (2 with Alzheimer's patients, 1 in mild cognitive impairment, and 5 with amyotrophic lateral sclerosis (ALS) patients)
• 4 observational studies of bipolar patients treated with pharmaceutical doses
• Numerous preclinical studies

Potential Benefit

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 neurodegenerative disorders [2][3]. Most of these mechanisms, however, have not been validated in humans and lithium did not live up to its promise as a neuroprotective treatment for ALS [4][5].

Long-term pharmaceutical use of lithium has been associated with a lower risk of dementia in several observational studies [6-8] and reduced rates of brain aging [9] for bipolar patients, though this pattern has not been seen in all studies [10].

For Dementia Patients

Two small clinical trials of lithium reported little to no cognitive benefit and substantial risks of side effects for Alzheimer's patients [11][12]. One double-blind randomized controlled trial, though, reported that a low pharmaceutical dose for one year improved the cognitive abilities of elderly people with mild cognitive impairment. The dose used was roughly half that of the typical therapeutic dose for bipolar disorder [13]. The study was too small to determine whether lithium prevented progression to Alzheimer's disease, but it appeared to reduce tau tangles [13], a component of Alzheimer's disease. However, safety concerns and the conflicting evidence on brain health warrant more research.

Safety

At high doses, lithium can cause short-term toxicity and severe long-term side effects, including kidney damage. 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-inflammatories, caffeine, theophylline, antidepressants, and anti-hypertensive medications can interact with lithium [14-16].

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 the salt, 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

Dietary Lithium report on Cognitive Vitality

Research Brief: Lithium for ALS—Another Nail in the Coffin? from AlzForum

Lithium: Oral Route safety precautions from the Mayo Clinic

Lithium safety precautions and drug interactions from Drugs.com

References

  1. Malhi, G.S., et al., Potential mechanisms of action of lithium in bipolar disorder. Current understanding. CNS Drugs, 2013. 27(2): p. 135-53.
  2. Fornai, F., et al., Autophagy and amyotrophic lateral sclerosis: The multiple roles of lithium. Autophagy, 2008. 4(4): p. 527-30.
  3. Sarkar, S. and D.C. Rubinsztein, Inositol and IP3 levels regulate autophagy: biology and therapeutic speculations. Autophagy, 2006. 2(2): p. 132-4.
  4. Group, U.K.-L.S., et al., Lithium in patients with amyotrophic lateral sclerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol, 2013. 12(4): p. 339-45.
  5. Gamez, J., et al., Lithium for treatment of amyotrophic lateral sclerosis: much ado about nothing. Neurologia, 2013.
  6. Nunes, P.V., O.V. Forlenza, and W.F. Gattaz, Lithium and risk for Alzheimer's disease in elderly patients with bipolar disorder. Br J Psychiatry, 2007. 190: p. 359-60.
  7. Kessing, L.V., J.L. Forman, and P.K. Andersen, Does lithium protect against dementia? Bipolar Disord, 2010. 12(1): p. 87-94.
  8. Gerhard, T., et al., Lithium treatment and risk for dementia in adults with bipolar disorder: population-based cohort study. Br J Psychiatry, 2015. 207(1): p. 46-51.
  9. Sajatovic, M., et al., Aging changes and medical complexity in late-life bipolar disorder: emerging research findings that may help advance care. Neuropsychiatry (London), 2013. 3(6): p. 621-633.
  10. Dunn, N., C. Holmes, and M. Mullee, Does lithium therapy protect against the onset of dementia?. Alzheimer Dis Assoc Disord, 2005. 19(1): p. 20-2.
  11. Hampel, H., et al., Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study. J Clin Psychiatry, 2009. 70(6): p. 922-31.
  12. Macdonald, A., et al., A feasibility and tolerability study of lithium in Alzheimer's disease. Int J Geriatr Psychiatry, 2008. 23(7): p. 704-11.
  13. Forlenza, O.V., et al., Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial. Br J Psychiatry, 2011. 198(5): p. 351-6.
  14. Grandjean, E.M. and J.M. Aubry, Lithium: updated human knowledge using an evidence-based approach: part III: clinical safety. CNS Drugs, 2009. 23(5): p. 397-418.
  15. D'Souza, R., et al., Use of lithium in the treatment of bipolar disorder in late-life. Curr Psychiatry Rep, 2011. 13(6): p. 488-92.
  16. McKnight, R.F., et al., Lithium toxicity profile: a systematic review and meta-analysis. Lancet, 2012. 379(9817): p. 721-8.