John Cade takes a chill pill

By Jeff Glorfeld

The World Health Organization (WHO) has declared 10 October to be World Mental Health Day, with an aim “to raise awareness of mental health issues around the world and to mobilise efforts in support of mental health”.

“There are many different mental disorders, with different presentations,” the WHO says. “They are generally characterised by a combination of abnormal thoughts, perceptions, emotions, behaviour and relationships with others.”

One of these issues, bipolar disorder, affects about 45 million people worldwide, according to the WHO. “It typically consists of both manic and depressive episodes separated by periods of normal mood. Manic episodes involve elevated or irritable mood, over-activity, rapid speech, inflated self-esteem and a decreased need for sleep. People who have manic attacks but do not experience depressive episodes are also classified as having bipolar disorder.”

The WHO says “effective treatments are available for the treatment of the acute phase of bipolar disorder and the prevention of relapse. These are medicines that stabilise mood. Psychosocial support is an important component of treatment.”

In a 2014 paper titled ‘Current Status of Lithium in the Treatment of Mood Disorders’, published in the journal Current Treatment Options in Psychiatry, researchers from the University of Sydney wrote that “arguably, lithium is the only true mood stabiliser and the only medication developed specifically for the treatment of bipolar disorder”.

The paper’s authors included the modifying adverb ‘arguably’ because “the clinical use of lithium has diminished in recent years because of displacement by newer agents and erroneous concerns regarding long-term side effects and potential for toxicity”.

However, they wrote that there was “a burgeoning body of both empirical and scientific research establishing its efficacy. Currently, lithium is experiencing a resurgence of interest as researchers attempt to understand its mechanisms of action and better define its clinical efficacy”.

Read more: Genetic link found between bipolar and schizophrenia

The discovery – or, rather, “rediscovery”, as the paper’s authors note – of the therapeutic benefits of lithium as a mood-stabilising agent was made in 1949 by Australian scientist John Cade.

The US National Public Radio, in a review of Walter Brown’s 2019 biography, Lithium: A Doctor, A Drug and a Breakthrough, said scientists first isolated lithium a century before Cade’s discovery.

“Doctors noticed that the element could dissolve uric acid, which was blamed at the time for a wide variety of illnesses, and lithium was used to treat everything from headaches to obesity,” NPR suggested. “For a while, lithium water was a popular cure-all, and lithium was once used as a salt substitute.”

A 2009 article published in the journal Bipolar Disorders highlighted Cade’s contribution. “The use of lithium in psychiatry goes back to the mid-19th century,” it said. “Early work, however, was soon forgotten, and John Cade is credited with reintroducing lithium to psychiatry for mania.”

John Frederick Joseph Cade was born on 18 January 1912 in Horsham, Victoria, and educated at Scotch College and the University of Melbourne, where he earned a medical degree in 1938.

An Australian Dictionary of Biography (ADB) article on Cade says he worked as a resident medical officer at St Vincent’s Hospital in 1935 and at the Royal Children’s Hospital in 1936, then joined the mental hygiene branch of the Department of the Chief Secretary and was appointed medical officer at Mont Park Mental Hospital.

Having served in the militia since 1935, Cade was made a captain in the Australian Army Medical Corps when World War II broke out, and was posted to Singapore in February 1941. A year later he was captured by Japanese forces and held in Changi prisoner-of-war camp until September 1945.

After the war, Cade returned to Victoria and joined the Department of Health, becoming medical superintendent and psychiatrist at the Repatriation Mental Hospital in Bundoora.

A Nature magazine review of Brown’s book said that while at Changi, Cade noticed a link between food deficiencies and diseases in his fellow prisoners.

In a 1967 article Cade wrote for Australian & New Zealand Journal of Psychiatry, he suggested that “there are few specifics in medicine. The specific anti-manic effect of the lithium ion is one. It was not an accidental discovery. It was the inevitable though unforeseen product of an hypothesis and of a series of experiments to test that hypothesis. The hypothesis was crude and the experimental methods were primitive. The work was done single-handed in a chronic mental hospital.”

The ADB describes how he experimented on guinea pigs, using a “disused kitchen” at the Bundoora hospital as his laboratory.

He collected urine samples from patients with depression, mania and schizophrenia, and injected it into the animals.

“He found that the animals became extremely lethargic and were protected from the toxicity of injected urea when lithium carbonate was given simultaneously,” the ADB says. “Taking lithium himself with no ill effect, he then used it to treat 10 patients with chronic or recurrent mania, on whom he found it to have a pronounced calming effect.”

Cade published the results of his research in the 3 September 1949 edition of The Medical Journal of Australia.

His “encouraging initial results are now widely considered a revolutionary discovery, although this innovative and effective treatment was not immediately adopted by psychiatry”, according to a 2019 article published by the International Journal of Bipolar Disorders.

It said Cade understood the reason for initial tepid reactions to his research, telling interviewers that “a discovery by an unknown psychiatrist without research training, working in a small hospital for the chronically mentally ill, with primitive techniques and negligible equipment, could not attract much attention”.

John Cade died of cancer on 16 November 1980 in Melbourne.