Lithium: The mood normalizer

Have you ever questioned the reality of your feelings? Have you ever questioned why sometimes you are the life of the party, entertaining people with your witty commentary, making every one laugh and yet somehow in just a couple of hours you are shy, tired and feeling an emotion that cripples your strength? According to the world health organization an estimated 45 million people around the world experience something similar, perhaps even in a greater magnitude than what any of us can comprehend. These people are diagnosed with a mental illness known as bipolar disorder. Now with medical treatment, people with bipolar disorder can lead productive and fulfilling lives, however it is important to understand that this would not be possible without Dr. John Cade and his discovery of the first ‘mood normalizer’, lithium.

Formerly known as manic depression or manic depressive illness, bipolar disorder causes unusual and unpredictable changes in mood, energy, concentration and the ability to carry out day to day tasks. People suffering from bipolar disorder experience severe and crippling emotional states that occur for an extended period of time like days or weeks, often referred to as mood episodes. In the first half of the twentieth century, most doctors believed that people with chronic mental illness had a disease that was largely hereditary and involved brain abnormality. Electro shock was considered to be the primary treatment. Patients were often restrained and highly sedated during their maniac stages, almost always confined to the hospitals due to development of suicidal tendencies.

Because of his upbringing on the grounds of a mental asylum, John Cade grew up among people with severe mental illness, through which he developed an empathetic approach to the needs of the mentally ill. Later following in his father’s footsteps he opted to join psychiatry. It was at Beechworth mental hospital where Cade began his career in psychiatric research.

John Cade was what his close acquaintances would describe as “one of observation.” He was often quick to notice things that others would not. It was his empathetic approach towards patients that led him to observe that most of them bruised easily. He often wondered if excessive force was being used on them, but later discovered that most patients were suffering from vitamin C deficiency. A situation he sought to rectify immediately.

In 1939, Cade joined the Australian military and was held as a prisoner of war in the infamous Changi prison. His powerlessness to help the prisoners suffering from severe PTSD and chronic depression further enlightened him on the lack of definitive treatment for the mentally ill. While performing autopsies, Cade’s belief of bodily changes resulting in mental disturbances was solidified. He believed that the patients suffering from bipolar disorder may lack certain key chemical substances or may have some unwanted ones in their bodies. Thus he began testing patient’s urine, in which he found an additional component of uric acid which is not seen in normal people. He began testing this acidic urine on guinea pigs which proved to be lethal in animals. With no access to sophisticated chemical analysis and on the basis of a largely intuitive or observational theory, he conducted experiments through which discovery of lithium carbonate as a possible cure was made. Lithium carbonate reduced toxicity in the patient’s urine. After testing it on guinea pigs, he found that lithium carbonate seemed to calm these balls of energy.

Later he administered the drug on himself for safety, and then began dosing his patients with lithium and the miraculous lithium therapy came into existence. His patients began showing significant improvement. Bill Brand was a patient at the asylum in Bundoora for more than 30 years. Over the duration of two months, this infamous patient was seemingly sane and left the hospital. However in the coming years, Cade himself abandoned the experiment, when one of his patients died due to a high dose of lithium.

Further, Edward Trautner measured the lithium level in blood of patients using flame photometry and confirmed Cade’s observation. He also identified the safe concentration of lithium in blood. Due to the efforts of a Danish psychiatrist- Mogens Schou who, intrigued by Cade’s claim, performed experiments that demonstrated lithium’s effectiveness. He also coined the term mood normalizer which explained that lithium was acting specifically on a disease rather than a symptom. Baastrup and Schou jointly conducted lithium trials and saw significant prophylactic activity against major psychosis. In bipolar disorder, atrophy and neuronal /glial stress is observed. There is a decrease in the gray matter volume in brain areas implicated in emotional processing and cognitive gyrus. When treated with lithium therapy, most studies find that there is an increase in gray matter volume in areas that process emotions. Although there is much debate regarding the use of lithium to treat bipolar disorder, this is no denying that lithium paved the way for other antipsychotic medication and introduced a new approach to the treatment of mental illness. Cade’s discovery prevented millions of suicides and saved the world economy from hundreds of million dollars in hospitalization costs thus becoming a scientific discovery that effectively tackled an issue that affected the society at large.


Lithium: A Doctor, a Drug, and a Breakthrough Walter A. Brown Liveright (2019)

Written by Priyanka Tiwari

Bachelors in Pharmaceutical Sciences

Savitribai Phule Pune University



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