New Study Shows No Evidence That Depression Is Caused By A Chemical Imbalance

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In Brief

  • The Facts:
    • A new review of existing studies found that depression is not likely to be caused by a chemical imbalance and said people should be made aware of other options for treating it.

    • Scientists found research that compared levels of serotonin and its breakdown products in the blood or brain fluids were no different between people diagnosed with depression and healthy people.

  • Reflect On:
    • How come the information presented in this article is not really known by most people?

    • Why do so many people believe that antidepressants are completely harmless and useful?

    • Do we really understand exactly how they change our brain chemistry?

    • Are those who have had positive experiences with antidepressants experiencing the placebo effect?

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Researchers and scientists have long questioned the widespread use of antidepressants. Not only for lack of efficacy, but for the harms associated with them as well. They’ve also questioned the premise for the prescription of these drugs, mainly the theory that depression is caused by a chemical imbalance in the brain. For decades this theory has permeated the world of health and been accepted as truth despite very little evidence. As a result, antidepressant drugs have become a multibillion dollar industry.

A new study published in the journal Molecular Psychiatry looked at studies examining serotonin and depression involving tens of thousands of people. Scientists found that research that compared levels of serotonin and its breakdown products in the blood or brain fluids were no different between people diagnosed with depression and healthy people. This comes despite the fact that up to 90% of the public believe that depression is caused by low serotonin or a chemical imbalance.

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The idea that serotonin might be involved in depression was first proposed in the 1960s, and became known as the serotonin theory of depression. The public messaging started in the 1990s when the pharmaceutical industry was marketing its new range of antidepressant drugs, the SSRIs (Selective Serotonin Reuptake Inhibitors) such as Prozac.

The study’s lead author, Joanna Moncrieff, a professor of psychiatry at University College London and consultant psychiatrist at North East London NHS foundation trust explains,

“Many people take antidepressants because they have been led to believe their depression has a biochemical cause, but this new research suggests this belief is not grounded in evidence….It is high time to inform the public that this belief is not grounded in science.”

Joanna Moncrieff, a professor of psychiatry at University College London

The authors also looked at studies where serotonin levels were artificially lowered in hundreds of people and concluded that lowering serotonin in this way did not produce depression in hundreds of healthy volunteers.

This is quite concerning given the fact that drugs like antidepressants change normal brain chemistry. They blunt both negative and positive emotions, and multiple studies have shown that that they may only act through inducing hope (the placebo effect). These concerns have been permeating medical literature for years.

A New England Journal of Medicine review on Major Depression from 2005 is one of multiple examples,

 “… numerous studies of norepinephrine and serotonin metabolites in plasma, urine, and cerebrospinal fluid as well as postmortem studies of the brains of patients with depression, have yet to identify the purported deficiency reliably.”

People need this information in order to make properly informed decisions about whether or to take antidepressants or seek alternative methods.

“Our view is that patients should not be told that depression is caused by low serotonin or by a chemical imbalance, and they should not be led to believe that antidepressants work by targeting these unproven abnormalities. We do not understand what antidepressants are doing to the brain exactly, and giving people this sort of misinformation prevents them from making an informed decision about whether to take antidepressants or not.”

Joanna Moncrieff, a professor of psychiatry at University College London

This research begs the question,  why was the idea that serotonin is the cause or part of the cause of depression so widely endorsed in the scientific literature in the 1990s and 2000s?


The best explanation seems to be clever marketing. In 2012, the NEJM published 73 articles on original studies of new drugs, which represented drugs approved by the FDA since 2000. It was found that 82 percent of them had been funded by the pharmaceutical company selling the product, and 68 percent of them had authors who were employees of that company. Finally, it was found that 50 percent had lead researchers who accepted money from a drug company.


study published in the Journal of Clinical Epidemiology looked at 185 meta-analyses on antidepressant medication and found that one third of them were written by pharmaceutical industry employees and that almost 80 percent of the studies had industry ties.

In 2010 Pfizer was ordered to pay $142 million US in damages for fraudulently marketing an anti-seizure drug called gabapentin, which was marketed under the name Neurontin. Pfizer was caught “fraudulently” marketing the drug “and promoted it for unapproved use.” It was discovered that the drug was promoted by the drug company as a treatment for pain, migraines and bipolar disorder, even though it wasn’t effective in treating these conditions and was actually toxic.

In 2012, GSK paid a $3 billion fine for bribing doctors and illegally promoting drugs for off-label uses. GSK withheld clinical trial results that showed its antidepressant, Paxil, not only doesn’t work for adolescents and children but more alarmingly that it can increase the likelihood of suicidal thoughts in this group.

study published in the British Medical Journal  by researchers at the Nordic Cochrane Center in Copenhagen showed that pharmaceutical companies were not disclosing all information regarding the results of their drug trials. Researchers looked at documents from 70 different double-blind, placebo-controlled trials of selective serotonin reuptake inhibitors (SSRI) and serotonin and norepinephrine reuptake inhibitors (SNRI) and found that the full extent of serious harm in clinical study reports went unreported.

“[This study] confirms that the full degree of harm of antidepressants is not reported. They are not reported in the published literature, we know that – and it appears that they are not properly reported in clinical study reports that go to the regulators and from the basis of decisions about licensing.”

Joanna Moncrieff, a professor of psychiatry at University College London

American pharmaceutical giant Gilead has paid at least $178 million to doctors and $81 million to hospitals in the US to promote and prescribe the company’s drugs despite cases of deaths and severe side effects. The drug-maker funded as many as 21,833 physicians in 2019 alone, according to data about Gilead payments from 2013 to 2019.

“And where there is a scientific vacuum, drug companies are happy to insert a marketing message and call it science. As a result, psychiatry has become a proving ground for outrageous manipulations of science in the service of profit.” 

Daniel J. Carlat, M.D., Associate Clinical Professor of Psychiatry at Tufts University School of Medicine

The Takeaway

When it comes to issues such as depression, nutritional, holistic and mindful interventions never really see the light of day and are never really discussed or recommended by your everyday psychiatrist.

In today’s day and age, self education is a must, and that goes for doctors as well.  When it comes to solutions to these issues, one must also consider options outside of the pharmaceutical industry and dive into other resources to seek out interventions that may not be motivated by profit. This is why awareness is key. As more people become aware of this type information they begin to seek out alternatives and make new choices.

It would be helpful if more effort and funding was applied to study other interventions that may not provide profit for the pharmaceutical industry. Perhaps this also shows the limitation in basing public well being on a capitalistic economy. Perhaps it’s simply a measure of our societal worldview.

Depression may not be a problem with brain structure, chemical flow and neurotransmitters. Instead, the mood of depression we experience comes from other factors that in turn may lead to changes in biology, brain structure, chemical flows etc. Mainstream medicine does not identify this issue, because the issue is not biological and is instead rooted in human experience, trauma, how one perceives the world and so much more, but that’s a discussion for another article.

Despite all of this emerging information, many health experts still emphasize the success and efficacy of antidepressant drugs.

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