John Cade - Discovery of The Effect of Lithium On Mania

Discovery of The Effect of Lithium On Mania

After the war, Cade recuperated very briefly in Heidelberg Hospital, then took up a position at Bundoora Repatriation Mental Hospital in Melbourne. It was at an unused kitchen in Bundoora where he conducted crude experiments which led to the discovery of lithium as a treatment of bipolar disorder. These experiments mostly consisted of injecting urine from mentally ill patients into the abdomen of guinea pigs. These would appear to die faster than when healthy persons' urine was used, leading him to think that perhaps more uric acid was present in the samples provided by his mentally ill patients. Then, in an effort to increase the water solubility of uric acid, lithium urate was added to the solution. Cade found that in the guinea pigs injected with the lithium urate solution, toxicity was greatly reduced. However, his use of careful controls in his experiments revealed that the lithium ion had a calming effect by itself. After ingesting lithium himself to ensure its safety in humans, Cade began a small-scale trial of lithium citrate and/or lithium carbonate on some of his patients diagnosed with mania, dementia præcox or melancholia, with outstanding results. The calming effect was so robust that Cade speculated that mania was caused by a deficiency in lithium.

While Cade's results appeared highly promising, side-effects of lithium in some cases lead to non-compliance. Toxicity of lithium led to several deaths of patients undergoing lithium treatment. The problem of toxicity was greatly reduced when suitable tests were developed to measure the lithium level in the blood. Moreover, as a naturally-occurring chemical, lithium salt could not be patented, meaning that its manufacturing and sales were not considered commercially viable. These factors prevented its widespread adoption in psychiatry for some years, particularly in the United States, where its use was banned until 1970.