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Study finds that 'chemical imbalance' in depression is a myth

There is no evidence of deficiency of serotonin in depression, authors report, refuting a belief held by 80% of the public. The misconception, long invoked as a reasoning for long term use of SSRI medications, has been known for over a decade, critics say, but psychiatrists have not made an effort to formally inform the public.

A new study by researchers at the University College of London has confirmed that there is no basis to the belief that depression is caused by a deficiency of serotonin or a chemical imbalance in the brain.
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ROCHESTER, Minn. — A new, high-level scientific review has concluded there is "no consistent evidence of there being a relationship between serotonin and depression," refuting a widely held notion that antidepressants correct a "chemical imbalance in the brain."

The study, authored by a team of researchers from University College London and published in the journal Molecular Psychiatry, was greeted with widespread media coverage in the United Kingdom, including protest from critics worried that the paper could cause patients to avoid seeking help or to stop taking antidepressant medications.

The study did not refute the legitimacy of clinical depression, however, nor the effectiveness of antidepressant drugs, which are taken by more than 1 in 10 American adults and which are shown to raise the availability of the neurotransmitter serotonin. The new study only refuted how the medications work.

That is, however, a substantial reversal, given that surveys show 80% of the public believe depression to be caused by a low-serotonin chemical imbalance in the brain, and that "chemical imbalance" reasoning has likely provided the basis for countless treatment decisions as well as years-long use of the medications.

“It is always difficult to prove a negative," said lead author Dr. Joanna Moncrieff in a statement , "but I think we can safely say that after a vast amount of research conducted over several decades, there is no convincing evidence that depression is caused by serotonin abnormalities, particularly by lower levels or reduced activity of serotonin."


Citing the potential for withdrawal effects, the authors cautioned that patients on selective serotonin reuptake inhibitors — or SSRI — should not attempt to stop taking their medication without the assistance of a health professional.

Myth first debunked in 2005

The so-called "umbrella study" amasses an exhaustive collection of findings opposing a message first debunked over a decade ago, following publication of an influential research paper which itself failed to overcome popular belief in serotonin deficiencies.

"I can't emphasize enough how astonished a good proportion of my students are to hear what was just expressed in this very well done paper," said Jeffrey LaCasse , associate professor in the College of Social Work at Florida State University. "They are astonished and they feel betrayed."

As coauthor within Jonathan Leo of "Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature," a paper published in the journal PLOS Medicine in November 2005 , LaCasse says he regularly asks his college students if they have heard the idea of a serotonin abnormality in depression presented as fact in the last 10 years.

"It's always more than half the class," LaCasse said in an interview with Forum News Service. "I think it often goes back to those Zoloft ads," he said, referring to the animated "Sad Blob" advertisements which famously said “depression may be related to an imbalance of naturally occurring chemicals" within the brain.

"They went off the air in 2006 or 2007," LaCasse said. "But I think it's a bit of an issue of, how do you put the toothpaste back in the tube?"

In the 17 years since its publication, "Serotonin and Depression" has been cited in more than 250 academic papers and viewed more than 300,000 times. But academic interest has proven ineffectual in the face of popular belief.

"It is a very attractive narrative," LaCasse says of the chemical imbalance narrative. "I am a big 'Sopranos' fan, and you can find multiple conversations among the characters about their serotonin imbalance."


Leo, an associate professor of anatomy at Alabama College of Osteopathic Medicine, says medical societies should correct the falsehood.

"I don't think psychiatrists have explained this to the general public," Leo said. "My feeling is that psychiatrists have known all along that there's no proof of a serotonin deficiency in depression, but they haven't wanted to clarify it for the general public. They could have easily clarified it in the last 10 years."

"This was Jon's point many years ago," LaCasse said. "That one prominent psychiatrist could have written an op-ed in The New York Times and ended the whole thing, and they never did."

LaCasse believes the myth has become entangled with other variables that go into prescribing.

"I think they have linked this theory to the efficacy of the drugs," he said, "which does not necessarily have to be linked. You could say, 'we don't understand what causes depression.'"

"You could say, 'we don't understand how the drugs work exactly, but they do help some people.' Instead, they've sold a magic-bullet narrative. This leaves them kind of holding the bag now, I think."

"We have seen other reversals in science," he adds hopefully. "You can think of the diet wars, and how the American Heart Association went from implicating fat to now talking about sugar, which was a reversal."

"When Jon and I wrote this paper in 2005, we never thought we'd be discussing this as something patients were told 17 years later."


Editor's note: Reporter Paul John Scott attended Macalester College in St. Paul with Jonathan Leo in the 1980s.

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Paul John Scott is the health reporter for NewsMD and the Rochester Post Bulletin. He is a novelist and was an award-winning magazine journalist for 15 years prior to joining the FNS in 2019.
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