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“. . . by the late 1980s . . . the chemical imbalance theory of depression . . . should have been dead in the water. Yet, it managed to survive long enough to be revitalized by the pharmaceutical industry a few years later in the interests of marketing the new generation of blockbuster drugs: the SSRIs. In the process, the theory was transformed from an unsubstantiated supposition into what was perceived as a scientific truth, and this was what persuaded subsequent generations to flock to their doctors to get pills for depression.”
—Joanna Moncrieff, Chemically Imbalanced, 2025.
While it is debatable as to exactly which of the many war-mongering lies told by politicians has resulted in the most disastrous outcome, when it comes to falsehoods declared by the psychiatry establishment and their Big Pharma partners, it would be difficult to find one that has created more damage than the chemical imbalance theory of depression—harming not only individual patients but society. This is the subject of psychiatrist Joanna Moncrieff’s recently published Chemically Imbalanced: The Making and Unmaking of the Serotonin Myth.
Moncrieff is a consultant psychiatrist for the National Health Services (NHS) in England, Professor of Critical and Social Psychiatry at University College London, and co-chairperson of the Critical Psychiatry Network.
In 2022, Moncrieff was the lead author of a landmark review of research studies that showed that there is no evidence that depression is caused by a serotonin imbalance. This systematic analysis of the research became one of the most widely read and influential papers in recent times (ranked by the online influence tracker Altmetric in the top 5% of all scientific papers ever written). While Moncrieff’s conclusion was no surprise to those in the scientific community familiar with some of these studies, it was a shock to much of the public, which for decades had repeatedly heard the opposite message—that serotonin deficiency caused depression—from establishment psychiatry and antidepressant commercials. This made Moncrieff’s review “newsworthy” for the mainstream media (for example, CBS’s 2022 story “Depression is Not Caused by Low Levels of Serotonin, New Study Suggests”).
The huge reaction to her review made it clear to Moncrieff that the public had an interest in the entire story behind the serotonin myth. Chemically Imbalanced is a hugely important book in which Moncrieff provides a comprehensive account of the origin and a history of the chemical imbalance theory of mental illness; the lack of evidence for a serotonin theory of depression; the primary reason for its persistence despite lack of evidence (an irresistible tool of drug companies for the marketing of antidepressants); the ineffectiveness and adverse effects of antidepressants; andthe bizarre manner in which establishment psychiatry has defended itself and attacked Moncrieff for her truth telling.
While psychiatry has had other major debacles—for example, the inflated results of antidepressant effectiveness reported by the STAR*D study, replete with scientific misconduct—its dishonesty about the serotonin imbalance theory of depression has resulted in something even more insidious: a distorted view of the nature of our humanity that not only has had major negative treatment consequences but harmful cultural and political consequences as well.
Moncrieff and her co-researchers were not the first to bring to light studies showing that depression was unrelated to a serotonin deficiency, but what they achieved in their 2022 paper was to definitively reject this chemical imbalance theory of depression. In the 1998 book Blaming the Brain, psychologist Elliot Valenstein had provided a handful of studies showing this lack of a relationship between serotonin and depression, concluding, “Furthermore, there is no convincing evidence that depressed people have a serotonin or norepinephrine deficiency.” However, Moncrieff and her co-researchers, by analyzing all relevant studies since this theory was proposed, put the final nails in the serotonin-imbalance coffin.
The relationship between depression and serotonin has long been studied through various means. The most direct method is to measure the breakdown product of serotonin (serotonin’s metabolites) of depressed and nondepressed subjects. Moncrieff and her co-researchers identified two systematic reviews of such research that included 19 separate studies, and she reported, “Neither of these reviews found any overall difference in the level of the breakdown product in people with depression compared to people without depression. So, the most direct method we currently have of assessing brain levels of serotonin suggests there is no difference between people with depression and people without depression.”
A less direct area of research consists of depleting the supply of serotonin’s precursor (its parent molecule) called tryptophan, and examining whether this depletion creates depression. Moncrieff reports, “None of the ten more recent studies we sampled detected any effect of the tryptophan-depletion technique on mood in healthy volunteers, either. Hence, the evidence does not suggest that reducing brain serotonin by tryptophan depletion induces depression in people who are not depressed. . . So, tryptophan-depletion studies do not support the serotonin theory of depression.”
So, if Moncrieff and her co-researchers only confirmed what researchers in the scientific community had already suspected—that depression was unrelated to serotonin levels or any such so-called chemical imbalance—why did she get attacked, sometimes viciously so, by establishment psychiatry? Chemically Imbalanced answers this question.
Establishment psychiatry and Big Pharma have long used this chemical imbalance/serotonin-deficiency theory to convince depressed patients to take drugs that increase serotonin levels; these are called selective serotonin reuptake inhibitors (SSRIs), with the well-known SSRI brand names including Prozac, Zoloft, Paxil, Celexa, and Lexapro, all of which have been blockbuster, multi-billion dollar grossing drugs. Even though Moncrieff and her co-researchers in their 2022 paper didn’t deal with antidepressant issues of scientific ineffectiveness and adverse effects, given how hugely important this serotonin imbalance theory is to patient antidepressant compliance, establishment psychiatry and Big Pharma were upset that Moncrieff’s exposure of the falseness of the serotonin imbalance theory became widely reported.
Establishment psychiatry’s attacks on Moncrieff were bizarrely inconsistent. She notes: “They played down the significance of the paper, and when that didn’t work, they tried to discredit it. Some insisted no one believes the serotonin theory of depression in any case, while others claimed serotonin does play a role in depression but couldn’t specify what that might be.”
Some key figures in establishment psychiatry attempted to convince the general public that Moncrieff was merely saying what psychiatry has long been saying. David Hellerstein, Professor of Clinical Psychiatry at Columbia University Medical Center and director of Columbia’s Depression Evaluation Service, claimed Moncrieff’s review “was largely met with yawns from the psychiatric community,” and he then sarcastically mocked her, “Wow, next she’ll tackle the discrediting of the black bile theory of depression.” This type of attack made little sense to the mainstream media and much of the general public who had not heard anything about this theory having been discarded. And the belittling of Moncrieff as saying nothing new appeared even more bizarre a year after her paper’s 2022 publication when in April 2023, the then president of the America Psychiatric Association (the guild of American psychiatrists) repeated a version of the serotonin imbalance theory, telling a podcaster, “We know that serotonin has been strongly associated with depression” and antidepressants “work on neurotransmitters, the chemicals in our brain, to rebalance the relative levels.”
While some key members of establishment psychiatry said that Moncrieff’s disproof of the serotonin imbalance theory of depression was nothing new, and others continued to espouse this theory, still others said that serotonin’s relationship with depression is “more complicated” than a simple imbalance. The only consistent response to Moncrieff’s review from establishment psychiatry has been that it doesn’t matter what Moncrieff reported because antidepressants “work”; and establishment psychiatry has been successful getting much of the mainstream media to buy this (for example, on November 8, 2022, the New York Times published “Antidepressants Don’t Work the Way Many People Think”).
There is a parallel to how establishment psychiatry has handled the invalidation of the serotonin-imbalance theory.Neoconservative enthusiasts for the 2003 U.S. war in Iraq had offered several false justifications for invading Iraq, the most compelling one for much of the U.S. public was their certainty that Saddam Hussein had weapons of mass destruction (WMDs). Even after it was clear that this WMD claim was false, an American Enterprise Institute article, “Why Neoconservatism Was and Is Right” (2010) was unapologetic: “Critics attack Operation Iraqi Freedom because intelligence regarding Iraq’s weapons of mass destruction proved wrong. . . . Post-war inspectors found no nuclear and few chemical and biological weapons, but they did find documents and presidency minutes which show with absolute certitude that Saddam Hussein was determined to reconstitute his weapons of mass destruction program as soon as sanctions collapsed.” So no WMDs found, but we were told it’s more complicated; and no serotonin imbalance found, but are now told it’s more complicated.
Moncrieff, in response to psychiatry’s attacks on her, invokes a more playful comparison than neoconservative war mongers—Sigmund Freud’s story of the borrowed kettle. A man is accused by his neighbor of returning a kettle in a damaged condition, and the man offers three conflicting excuses: that the kettle wasn’t really damaged, that it was already damaged when he borrowed it, and that he never borrowed it in the first place!
A handful of research psychiatrists have viewed the serotonin imbalance theory of depression as essentially a “noble lie” that enabled people to feel better about their depression and take their antidepressants. While establishment psychiatry did not use the “noble lie” defense following Moncrieff’s exposure of the lack of evidence for the serotonin imbalance theory, some have previously used it (“Psychiatry’s Manufacture of Consent”). Alan Frazer, professor of pharmacology and psychiatry at the University of Texas Health Sciences Center, told NPR in 2012 that by framing depression as a deficiency—something that needed to be returned to normal—patients felt more comfortable taking antidepressants, “If there was this biological reason for them being depressed, some deficiency that the drug was correcting, then taking a drug was OK.”
The noble lie rationale begs two questions. First, is it ever ethical to tell patients falsehoods? Second, even if you accept the idea that some lies to patients can be ethical, has the serotonin imbalance theory of depression falsehood been a “noble lie”? In other words, has it resulted in more or less individual and societal misery and suffering? In Chemically Imbalanced, Moncrieff thoroughly answers the question of whether it has been a good or bad thing to convince people to believe that their depression was a biological-chemical event, which persuaded them to use SSRIs and other so-called antidepressants.
One argument for biological-chemical and other brain-disease theories of depression is these reduce stigma. “However,” Moncrieff points out, “there is a considerable volume of research showing that regarding mental health problems as brain diseases leads to more, not less stigma. Numerous attitude surveys have shown that when people are presented with biological explanations for mental illness, as compared to psychological or social explanations, they are more likely to think of the sufferer as being dangerous, as having no chance of recovery and are less likely to want to get acquainted with them.”
To be clear, Moncrieff is not anti-drug, but rather anti-bullshitting patients about psychiatric drugs. While antidepressants don’t work by correcting any mythical chemical imbalance, it is true that studies show that from 25 to 35 percent of depressed patients report short-term benefits; however, those receiving a placebo do just as well. And in the long term, more depressed people remit from depression without antidepressants than by using them.
When taking antidepressants, as is the case with any psychotropic drug, there is going to be a placebo effect, and because of the noticeable side effects of antidepressants, this placebo effect is what scientists call an “amplified” one. Moncrieff notes, “Alongside placebo and amplified placebo effects, there is the possibility that antidepressants improve people’s depression scores by numbing their emotions . . . . People frequently described a numbing or blunting of emotions . . . . They reported being less in touch with their feelings, being unable to cry, feeling uncaring or unmotivated, and some felt they were no longer themselves.”
Some people, at least for a time, might prefer this emotional blunting, but this is not curing depression. Moreover, antidepressants create all types of adverse effects, including sexual dysfunction and severe withdrawal problems, especially with long-term use.
Beyond the individual patient consequences of antidepressants, there are societal and political ones. Moncrieff notes: “Not only does it expose people to the unpleasant and sometimes dangerous and incapacitating effects that arise when the body has to deal with an alien substance, it lets society off the hook.”
Faux-left liberals have supported establishment psychiatry’s biochemical-medicalization of depression and attacked Moncrieff (see my 2022 CounterPunch article “Behind Rolling Stone’s Hatchet Job on a Psychiatrist Critical of Neoliberal Capitalism”). In contrast to the faux-left, the anti-authoritarian left, including Moncrieff, has long recognized that such medicalization serves to maintain a societal status quo that is causing much of our suffering.
“Whether it is neoliberal capitalism or some other economic system,” Moncrieff points out, “the transformation of social, political and personal problems into the medical domain is profoundly conservative (with a small ‘c’). It buffers whatever political philosophy and economic regime currently exists—whether that be of the Left or Right—against legitimate criticism.”
The falsehood of the serotonin imbalance theory is disempowering on both an individual and societal level. “The medical approach doesn’t help people find solutions to their problems,” Moncrieff notes, as “it substitutes a careful understanding of each individual’s predicament with a diagnostic label. And rather than providing the social support and community that most people need, it discourages people from understanding the social implications of their feelings and hinders them from reaching out to others to find collective solutions. . . . ultimately, mental health problems like depression and anxiety are social and political problems. If we wish to tackle them, we need as a society to prioritise addressing the circumstances that give rise to them.”
One of the most damning indictments of establishment psychiatry is that it takes courage for psychiatrists to assert scientific truths about their profession because the psychiatry establishment resembles far less a scientific community than a fundamentalist organized religion. Retributions against psychiatrists critical of their profession have not been as violent as what Galileo experienced in 1633, when he was tried by the Roman Catholic Church for heresy and forced to recant under the threat of death; however, when the psychiatry establishment cannot simply ignore its critics, it will belittle and marginalize them. Among the handful of brave psychiatrists who have made establishment psychiatry uncomfortable with inconvenient truths—a short list that includes Thomas Szasz, Ron Leifer, Loren Mosher, Peter Breggin, David Healy, Grace Jackson, and a very few others—all have paid a price with the loss of academic and other professional positions or have been punished in some other manner by establishment psychiatry.
Observing establishment psychiatry’s attacks on its critics for several decades now, the only relatively “good news” I can offer to future brave psychiatrists is that establishment psychiatry’s style resembles much more the Donald Trump/Roy Cohn strategy—attack, never acknowledge guilt, and always claim victory—than it resembles the Inquisition strategy used on Giordano Bruno. So, if you are young psychiatrist who aspires to be a freethinking truth teller, you will get verbally abused and jeopardize your career, but you need not fear being burned at the stake.
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