How lithium changed the history of psychiatry in one corner of the world while being banned in another

In July 1968, when Dr. Walter Brown began his psychiatry fellowship at Yale, his first mission was to prevent Mr. G from meeting with the President of the United States.

Mr. G was a patient who had spent the last 17 years in a psychiatric hospital, immobilized by suicidal depression or with a euphoria that made him think of a meeting with the country’s president.

“Several times a week, Mr. G would rush out the door. Three nurses and I had to drag him into a seclusion room where, as I wrestled with him, one of them gave him a sedative,” Brown wrote in his book “Lithium: A Doctor, a Drug, and a Breakthrough.” a doctor, a drug, a breakthrough).

The patient suffered from manic depressive psychosis either Bipolar disorder.

His prognosis was not at all auspicious, but two years later Brown met Mr. G again, and found a man who lived on his own, outside of hospitals, and worked in a supermarket.

He still remembered, between astonishment and shame, his desire to meet with the president.

A new drug had stabilized his mood swings: lithium.

There was born the psychiatrist’s interest in this alkaline metal and, above all, in the man who transformed it into the first psychiatric drug: John Cade.

from the big bangg to lithium fever

In the 21st century, lithium is spoken of as “the gold of the future” due to its use in batteries for electronic products and the automotive industry.

The search for alternative energy sources to replace fossil fuels has triggered a race for lithium, which is found in abundance in the salt flats of Bolivia, Chile and Argentina.

But the lightest of all metals has been with us since time immemorial. Scientists believe that next to hydrogen and helium they are the only three elements created with the big bang (both occupy the first three places of the periodic table that we all study in our Chemistry classes).

As James Russell describes in his book on this table, there are records of the therapeutic use of lithium dating back to the second century of our era, when the healer Soranus of Ephesus recommended baths in waterfalls of alkaline waters for those who suffered “from mania and melancholia”.

In the middle of the 20th century, lithium would once again be the key to treating these two states, that of being “very high” and that of being “very low”.

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Bipolarity can lead to mood swings that end up wearing down the patient’s mental health.

For Brown, two aspects are fundamental in this story: the characteristics of psychiatry up to the conversion of the lithium in drug and the context in which John Cade’s 1949 discovery occurred.

“Until that time, there were no drugs used for mental health, people used opioids, sometimes they were given stimulants or sedatives. Lithium was the first time that the symptoms of a psychiatric illness were effectively treated,” Brown tells BBC Mundo.

Treatments for manic depression and other mental health conditions included confinement in psychiatric hospitals, where coma could be induced from doses of insulin to sedation for deep sleep therapy; electrical convulsions were also applied and -in the 1940s and early 1950s- lobotomy was widely used.

Cade, on the other hand, was a young and unknown psychiatrist, a veteran of World War II, who worked in a hospital in Melbourne, Australia, without formal training, without scholarships and without collaborators.

His lab was in the hospital kitchen. There are those who say that his discovery was due to luck, but Brown does not entirely agree with this assessment.

“Part of the process, he was lucky; he began giving guinea pigs lithium salt and noted that this relaxed them. But we have to give him credit because he looked at this and thought it could work in people, in manic patients. Making this jump, to me, is very intuitive and reflects his abilities as an unbiased observer,” says Brown.

Eduard Vieta, head of the Psychiatry and Psychology Services at the University Hospital of Barcelona, ​​tells BBC Mundo that, although it now seems logical to us, Cade’s revolutionary idea was that he could treat mental illness with drugs, something not so obvious 70 years ago.

“He had a hypothesis, which was ultimately proven false, and that was that uric acid played a key role. As acids are not stable as drugs, you have to constitute them in the form of salt to be able to consume them. That’s where lithium comes into play. When he gave the guinea pigs lithium urate, he saw that they calmed down. But basically what he did was intoxicate the guinea pigs”, explains Vieta.

When Cade gave patients lithium urate, he found an improvement that he attributed to uric acid, not lithium.

“But later, when he tried other salts, he didn’t get the same result, and he was smart and deduced that it was lithium that had improved his patients,” adds Vieta.

lithium in blood

“I started out thinking I was going to write a biography of Cade, but as I researched I learned, for example, that Cade himself had put his work on hold due to his patients getting sick. And other people took the post. So I decided to do the story of a scientific discoveryof people who learned from other people, ”Walter Brown tells BBC Mundo.

Although the Australian psychiatrist’s 10 initial patients showed improvements in their mental health, very soon some of those patients suffered severe intoxications and Cade himself considered that lithium was dangerous and should not be prescribed.

Blood test

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Bipolar patients treated with lithium should have regular blood tests.

But then other doctors in Australia, like Edward Trautner, found that the amount of lithium in the blood could be measured of patients and thus avoid intoxication.

As Ricardo Corral, president of the Argentine Society of Psychiatry, told BBC Mundo, there is a “therapeutic window”, where -at a minimum- lithium is not effective and -at a maximum- it is toxic: “And in addition to doing the evaluation of therapeutic and collateral effects, the blood test allows us to know if the patient complies or does not comply with the treatment”.

For the psychiatrist Vieta, this progress made by Trautner and his team is another great advance in psychiatry that we owe to lithium:

“Lithium makes it necessary to monitor the plasma levels of the drug. That makes doing blood tests on psychiatric patients make sense. Enter, in some way, more medicine in psychiatry“.

But at the same time that in Australia they discovered how to deal with the toxicity of lithium, in the United States this toxicity was going to lead the government to withdraw it from all pharmacies, stores and even a well-known brand of soda.

fear of intoxication

Just as today we want to replace fossil fuels with lithium batteries to power our vehicles, 70 years ago someone thought it would be a good idea to use lithium to replace sodiumanother alkaline metal that is present in sea salt and, therefore, in the salt shaker of all kitchens.

Excessive sodium intake, as our doctors have always told us, can lead to high blood pressure, heart problems and kidney failure.

“In the late 1940s, people in the US began using lithium chloride as a salt substitute for those on a low-sodium diet. And a lot of them got intoxicated, they got poisoned and some of them died,” recalls Brown.

The Food and Drug Administration (FDA) has banned lithium and its use in other substances. Even was withdrawn fromand the soda 7 Upof which it was an ingredient (the original name of the drink was “Bib-Label Lithiated Lemon-Lime Soda”).

“The FDA sent its agents to remove it from pharmacy shelves, but that fear of lithium toxicity remained in the minds of doctors and the general public,” Brown tells BBC Mundo.

desperate person

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People with untreated bipolar disorder are more likely to commit suicide than other mental illnesses.

This contributed, according to this psychiatrist, to the fact that lithium is not prescribed for bipolarity in the US to the same extent as in other countries. But it is not the only factor:

“Also, in this country, a good number of pharmaceutical companies sold heavily other drugs to treat this disorder, with aggressive marketing and heavy promotion. And this had a big effect on lithium consumption. That is why it is estimated that in the US only 10% of patients who could benefit from the use of lithium actually use it, while in other countries, such as Europe, its use is 50%”, says Brown. Eduard Vieta agrees with this explanation and adds new causes to this mistrust.

“Lithium is a medicine orphan from a marketing and business perspective. And there is another factor that is litigation. We are talking about an old drug, with little glamour, but since it still requires a certain amount of care, then – if a patient accidentally poisons you – they can sue you”.

Boy takes a 7 Up in 1953

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In the early 1950s, lithium ceased to be used as an ingredient in 7 Up soda.

However, as psychiatrist Ricardo Corral explains, lithium serves not only to stabilize the patient but also to avoid one of the greatest dangers for those who suffer from bipolar disorder.

“In addition to improving mood, both in mania and depression, lithium reduces the risk of suicide,” explains the Argentine psychiatrist.

Suicide, megalomania and creativity

Bipolar disorder, explains the journalist Douwe Draaisma in the journal Nature, affects one in 100 people globally and, if left untreated, becomes a constant cycle of euphoria and depression, therefore, the risk of taking off the life is so high.

“The suicide rates for patients without treatment they are between 10 and 20 times higher than the rest of the population”, writes Draaisma.

“It is the disease that is associated with the highest risk of suicide. It is true that there are more suicides due to common depression, because this depression is more frequent, but having bipolar disorder carries a higher risk than any other disease”, confirms Vieta.

But even short of taking their own lives in depression, patients with this disorder can be at great risk when they seem enthusiastic and animated.

As the psychiatrist Iria Grande, secretary of the Spanish Society of Psychiatry and Mental Health, explains to BBC Mundo, in the most acute manic episodes, the state of euphoria can lead people to spend a lot of money or have megalomanic delusions.

“That is, you think outside of reality and believe that you have powers that are not necessarily real, such as having connections with God or being the savior of the world.”

Like the patient Mr. G, who thought he could meet with the president of the United States.


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Although the exact reason has not been defined, the link between creativity and bipolarity has several historical examples.

But not everything is as dark as suicide or delirium. This illness, as the psychiatrist Edward Vieta explains, has been linked to creativity of composers, artists, poets and writers:

“If we look at historical figures, there are many, some very well documented and others that are suspected diagnoses. (Robert) Schumann, for example, died in a psychiatric hospital, and clearly had manic and depressive episodes, to the point that we see that his compositions are grouped into years in which he is hypomanic, with a lot of energy, and in other times he is not. he composes nothing, because he is depressed”.

Grande recalls another historical case of the link between creativity and bipolarity:

“A very clear case is Virginia Wolf, who had very serious depressive episodes and whose manias were a small euphoria; she did not get to have thoughts that did not fit with reality, but his productivity is very related to these hypomanic episodes. And in episodes of depression I was not creative at all.

lithium sunset

Brown has described the discovery of lithium as the most relevant in the history of 20th century psychiatry.

“Then, in the 50s, other psychiatric drugs emerged, such as those used against schizophrenia, and at the end of that decade antidepressants, but lithium was the first,” he tells BBC Mundo.

Vieta prefers to talk about tennis:

“It’s like when a Federer, a Nadal and a Djokovic coincide. In the case of psychiatry, it is lithium, chlorpromazine -the first antipsychotic- and the first antidepressant. The first was surely lithium, but the one that has had a brutal impact on the history of psychiatry is chlorpromazinewhich is introduced into psychiatric hospitals and allows hundreds of thousands of patients to be discharged”.

Tom Wolfe

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In 1996 the journalist Tom Wolfe considered that lithium would imply the overcoming of psychoanalysis.

Interestingly, in 1996, the American journalist Tom Wolfe wrote his article “Sorry but your soul just died”, where he explored the revolution in neuroscience and antidepressant drugs.

In it he made reference to John Cade and considered his discovery to be largely responsible for the end of psychoanalysis:

“The demise of Freudian theories can be summed up in one word: lithium,” wrote the always controversial Wolfe.

But although lithium did not end psychoanalysis, it has changed the lives of thousands of patients since 1949, some from an early age, others – as the American poet Robert Lowell writes – when much of the damage of the disease had already been done:

“It is disturbing to think that I have endured and caused so much suffering because a little salt was missing in my brainand that if the effects of that salt had been known before, if it had been administered to me before, I could have had a happy life or in any case a normal life instead of this long nightmare.

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