Lithium for older adults with bipolar disorder: Should it still be considered a first-line agent?

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 beta 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.