In 1949, John Cade (1929–1996), an Australian psychiatrist serendipitously initiated a new era in psychiatric treatment by introducing lithium carbonate to treat mania. Initially, he reported on beneficial effects of treating ten patients with lithium carbonate (a medically accepted, though unproved, treatment for gout) for mania and on risks of discontinuing such treatment. These encouraging initial results are now widely considered to represent a revolutionary discovery, although this innovative and effective treatment was not immediately adopted by psychiatry.
In 1954, Professor Erik Strömgren (1909–1993), a prominent academic psychiatrist at the University of Aarhus Medical Center in Denmark, read of Cade’s experience with lithium for mania and asked his then-junior colleague Mogens Schou (1918–2005) to replicate the Australian findings. Schou not only did so, but pursued the study of lithium to contribute in a major way to establishing its safe and effective clinical use for the treatment of manic-depressive illness. His research in collaboration with another Danish psychiatrist, Poul Baastrup (1918–2001), established the most important effect of lithium—its ability to prevent recurrences of manic-depressive illness.

Gradually lithium became accepted in clinical practice around the world. It received regulatory approval by the US Food and Drug Administration (FDA) in 1970 for treatment of acute mania, and in 1974 as the first—and for many years, the only—approved treatment for prevention of recurrences in bipolar disorder.
Clinical applications of lithium were made possible by introduction of sensitive, reliable, quantitative methods of assay of lithium concentrations in serum, initially with flame spectrophotometry and later with atomic absorption, electrochemical, and other detection methods, to establish circulating concentrations of lithium required for safe and effective clinical dosing. Indeed, lithium remains unique in not being dosed adequately by the mg dose of drug given per day, but instead by achieving serum concentrations at their daily nadir (most stable range) on the order of 0.6–1.0 mEq/L.
Today, lithium treatment is still considered the “gold standard” of treatment for prevention of recurrences in bipolar disorder, both type I and II. It is also recommended for prevention of suicidal behavior in patients with bipolar or major depressive disorder. Fears about lithium treatment currently are most often directed to putative renal toxicity with its long-term use, although such effects are uncommon and can usually be anticipated by rising serum concentrations of creatinine or declining creatinine clearance.
For some patients and families, there may also be a personally “stigmatizing” effect of lithium treatments perceived as only for severely ill patients, in contrast to use of seemingly less stigmatizing anticonvulsant, antidepressant, antipsychotic and other psychotropic medicines. An important factor is that lithium salts, as unpatentable minerals of little commercial interest, have lacked pharmaceutical support for research and development and for assertive marketing.
Although lithium is effective in treating acute manic episodes, its primary value is as a “mood-stabilizing” agent, aiming at long-term prevention of recurrences of acute illness-episodes in bipolar disorder patients, with greater benefit against recurrences of mania than for bipolar depression. However, excellent responders to lithium treatment (3 years with no recurrences) are about one third of all treated patients.

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