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Lithium for Older Adults with Bipolar Disorder

Should it Still be Considered a First-Line Agent?

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Abstract

The use of lithium carbonate for the treatment of bipolar disorder in older adults is decreasing at a significant rate. This change in prescription pattern is occurring at a time when all evidence-based treatment guidelines and systematic reviews still recommend lithium as a first-line treatment for bipolar disorder.

Despite having the strongest evidence base for effectiveness, lithium does pose significant concerns in the older population, including the risk of drug interactions that cause toxicity associated with decreased creatinine clearance. The evidence for lithium’s impact on chronic renal disease is still controversial and is reviewed in this article. Mixed evidence exists regarding the impact of lithium on suicide risk, although there is a consensus that it does have protective properties through its mood-stabilizing effect. Because of the very limited research base regarding the use of lithium in old age, guidelines for dosing and maintenance of serum concentrations are not well established, and this may be leading to increased episodes of lithium toxicity.

At the same time that these legitimate concerns about lithium are being highlighted, evidence has accumulated that suggests that lithium may have neuroprotective properties. Its action of inhibiting the enzyme glycogen synthase kinase-3 may be responsible in part for a decrease in the induction of amyloid β peptide and hyperphosphorylated tau protein, which have been implicated in the development of Alzheimer’s disease.

Very little evidence supports use of alternatives to lithium such as other mood-stabilizing agents, including atypical antipsychotics, in older adults. Thus, before we abandon lithium as a first-line agent, we should ensure that the guidelines for lithium treatment are safe, practical and effective. Newer agents must be appropriately tested in older adults before replacing this longstanding first-line treatment for bipolar disorder.

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Acknowledgements

Dr Shulman is supported in part by the Richard Lewar Chair in Geriatric Psychiatry. No sources of funding were used to assist in the preparation of this article. The author has no conflicts of interest that are directly relevant to the content of this article.

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  1. Department of Psychiatry, Faculty of Medicine, University of Toronto, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5, Canada

    Kenneth I. Shulman

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Shulman, K.I. Lithium for Older Adults with Bipolar Disorder. Drugs Aging 27, 607–615 (2010). https://doi.org/10.2165/11537700-000000000-00000

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