The Manic Story of Lithium

Today's hero of psychiatry is John Cade, who spent much of World War II in a Japanese prison camp where he passed the time carefully observing the effects of vitamin deficiencies on his fellow prisoners.

After the war, he pursued his investigations. Working from an abandoned pantry in Bundoora Repatriation Mental Hospital near Melbourne, Australia, he began to collect urine samples from people with depression, mania and schizophrenia, aiming to discover whether some secretion in their urine could be correlated to their symptoms. With no access to sophisticated chemical analysis and largely unguided by theory, Cade injected the urine into the abdominal cavities of guinea pigs, raising the dose until they died. The urine of people with mania proved especially lethal to the animals.

In further experiments at Bundoora, Cade found that lithium carbonate — which had been used to treat conditions such as gout since the nineteenth century — reduced the toxicity of patients’ urine. Cade also noticed that a large dose of the medication tended to calm the guinea pigs. He could turn them on their backs, and the normally restive rodents would gaze placidly back at him. He wondered whether lithium could have the same tranquillizing effect on his patients. After trying it out on himself to establish a safe dose, Cade began treating ten people with mania. In September 1949, he reported fast and dramatic improvements in all of them in the Medical Journal of Australia. The majority of these patients had been in and out of Bundoora for years; now, five had improved enough to return to their homes and families.

If some weird guy on the Metro told you that lithium therapy was developed by injecting guinea pigs with human urine until they died, would you have believed him? But this is from Nature, a review of a new book about lithium by psychiatrist Walter Brown. Hard to find a better source.

Incidentally hardly anybody believed Cade's results when he published them, and even he gave up on lithium after one of his patients died of an overdose. It took another set of more orthodox psychiatrists to do the detailed studies and refine the dosing and so on to make lithium into a useful therapy.

In another incidentally, nobody has any idea how lithium works.

In a third, 7-Up used to contain lithium citrate, just like coca-cola used to contain cocaine.

And in the final incidentally, lithium carbonate is more common in the soils of East Africa where humans evolved than elsewhere, and it has been theorized that we evolved to need it and function better with a supplemental dose, which has led to calls to add lithium to drinking water.