The “Low Serotonin” Theory Of Depression Just Got Debunked — Here’s What That Means

Worried young woman lying on bed at home.

The medical myth was so accepted that it may have led many psychiatrists to mislead their patients.

The vast majority — 85-90% — of the public, not to mention swathes of the medical community, believes a “chemical imbalance” in the brain causes depression. Now, a major new peer-reviewed study reported in Psychology Today has decisively debunked the theory. We’ve broken down the study’s findings — plus what this means for our understanding of depression.

“No evidence of a connection”

For years, the medical community took for granted that a chemical imbalance in the brain — aka, low serotonin levels — is at the root of depression. The theory was so accepted that it went largely unchallenged for years, but a deep dive into the evidence has upended it.

In “The Serotonin Theory of Depression: A Systematic Umbrella Review of the Evidence,” published in Molecular Psychiatry, University College London Psychiatry, Professor Joanna Moncrieff and a team of top European researchers found “there is no evidence of a connection between reduced serotonin levels or activity and depression.”

The peer-reviewed umbrella study, one of the most trustworthy forms of evidence available, found that textbooks in wide use published as recently as 2020 have perpetuated the myth. The study found that “Research on serotonin receptors and the serotonin transporter, the protein targeted by most antidepressants, found weak and inconclusive evidence suggestive of higher levels of serotonin activity in people with depression.”

A more likely explanation

Widespread use of antidepressants — which have been falsely touted in language approved by the FDA to “restore the brain’s chemical balance” and “bring serotonin levels closer to normal” — is in fact the most likely cause of unusual serotonin levels in the population.

Rather than any relevant correlation with serotonin levels, stressful life events appear to be a strong predictor of depression. Per the review, “the more of these a person had experienced, the more likely they were to be depressed.”

These findings are acutely relevant considering that depression currently affects millions of adults in the United States. The 2020 National Survey on Drug Use and Health showed that 10.5% of females and 6.2% of males suffered a major depressive episode that year — an estimated total of 21 million adults. Those with mixed racial backgrounds had the highest instances of depression, at 15.9%.

So, how did we get here?

The low serotonin theory was first suggested in 1965 by Harvard psychiatrist Joseph Schildkraut. Its poor evidentiary basis didn’t prevent it from spreading widely — and being used by many psychiatrists and doctors as a convenient “shorthand” to explain tricky psychological issues to patients. Even though scientists over the years have pointed out the fact that there isn’t solid research to back the low serotonin theory, extensive marketing claims — and the idea that low serotonin could be an explanation for depression — pushed it into the mainstream.

The repetition of the theory by doctors to their patients, usually as a means of explaining why they were being prescribed antidepressants, throws up a significant ethical issue. While a simple “low serotonin” rationale may be comforting — and make it sound as though doctors know what they’re doing — it has meant that people taking antidepressants aren’t necessarily making an informed decision. 

Daniel Carlat, the editor of The Carlat Psychiatry Report, explained on National Public Radio (per Psychology Today): “Patients want to know something. And they want to know that we as physicians have some basic understanding of what we’re doing when we’re prescribing medications. They certainly don’t want to know that a psychiatrist essentially has no idea how these medications work.”

Is it still OK to take antidepressants?

Absolutely. As Christopher Davey points out in The Guardian, it’s not necessarily a problem if we don’t 100% understand how medications work. The important thing is that they do work, at least for some people.

The idea that low serotonin levels were linked to depression was actually born of the fact that antidepressants that affect serotonin levels were shown to be effective — so even if it turns out that they’re effective for a different reason, that’s still OK. It’s common for doctors to be aware that a treatment works before they clearly know why, and though SSRI antidepressants aren’t quite as effectual as we might hope, they are still demonstrably more useful than placebos.

The important thing for the millions of people with depression is that there is a range of treatment options available. For some people, medication might be an incredibly useful tool just on its own. For many, medication in conjunction with therapy might work better, and for others, therapy alone, or lifestyle changes, might be the best route. Flexibility is vital to tackling this pervasive condition, so always try to keep an open mind when it comes to trying new treatments.