Did Psychiatry Ever Endorse the Chemical Imbalance Theory of Depression?

In a new article published in the journal mental health, Benjamin Ang and his colleagues explore how psychiatry championed the debunked “serotonin theory” of depression, the assertion that lowered serotonin levels cause depression.

As the evidence against the serotonin theory of depression grows each day, many psychiatrists have claimed that the field never truly embraced this damaging and incorrect theory. To test whether psychiatry championed the serotonin theory of depression, the current work examines highly cited reviews of the causes of depression, highly cited papers that discussed depression and serotonin, and several textbooks published between 1990 and 2012. Despite contemporary psychiatrists’ claims to the contrary , all of the textbooks examined and nearly all academic papers supported this theory despite the lack of evidence.

“The findings suggest that the serotonin theory was endorsed by the professional and academic community,” the authors write. “The analysis suggests that, despite protestations to the contrary, the profession bears some responsibility for the propagation of a theory that is not empirically supported and the mass antidepressant prescribing it has inspired. “

Despite the psy-disciplines knowing that the serotonin theory was incorrect as far back as 1970, modern psychiatrists are still pushing this debunked theory, even as others claim the psy-disciplines never truly embraced it. The serotonin theory led to the common misunderstanding that depression was caused by a “chemical imbalance” in the brain, which led to an explosion in the sale of antidepressants to treat this supposed chemical imbalance. This series of events, paired with the lack of evidence for the serotonin theory, has caused some researchers to wonder if the serotonin theory was, in truth, a marketing scheme carried out by the pharmaceutical industry.

Although antidepressants are still commonly prescribed to treat depression, their efficacy is questioned. The little evidence that does exist is at high risk for bias. There is no evidence that antidepressants treat a “chemical imbalance” in the brain. The lack of evidence for antidepressant efficacy, paired with the mounting evidence of their detrimental effects, has caused some researchers to declare, “It’s time to stop recommending antidepressants for depression.”

The theory that chemical imbalance in the brain causes depression began in the 1960s. Researchers initially focused on noradrenaline rather than serotonin as the problematic neurotransmitter. However, serotonin replaced noradrenaline as the key neurotransmitter in the chemical imbalance theory in the late 1980s, just as pharmaceutical companies rolled out selective serotonin reuptake inhibitors.

In the 1990s, the pharmaceutical industry began branding depression as an aggressive imbalance of serotonin in the brain and SSRIs as a “magic bullet” that could correct this problem. The American Psychiatric Association parroted this pharmaceutical industry misinformation in a 2005 patient leaflet declaring, ““may be prescribed to correct imbalances in the levels of chemicals in the brain.”

The branding of depression as a chemical imbalance and SSRIs as the remedy has paralleled a massive increase in antidepressant prescriptions. According to the authors, belief in the debunked chemical imbalance theory is common among people using antidepressants. This belief also encourages people to request antidepressants and discourages them from trying to stop taking these drugs.

In 2005, Jeffrey Lacasse and Jonathan Leo published a paper detailing the disconnect between pharmaceutical industry advertising and what the evidence actually said about chemical imbalance theory. This paper inspired prominent psychiatrists to defend the debunked theory by explaining that a “chemical imbalance” was a metaphor rather than a literal description of reality. As the evidence against chemical imbalance theory, many within the psy-disciplines began claiming that psychiatry had never truly embraced “chemical imbalance theory” but that it was instead pushed by the pharmaceutical industry directly to the public with little involvement from the psy-disciplines .

The authors investigate the claim that the psychiatric profession did not promote serotonin theory by analyzing research articles and textbooks published between 1990 and 2012. The current research examines 30 reviews of the causes of depression, 30 highly cited papers that explored the connection between serotonin and and a sample of depression texts.

23 of the 30 reviews discussed the chemical imbalance theory of depression. And 2 of the seven that did not discuss chemical imbalances were explicitly dedicated to environmental factors of depression. Eleven reviews thoroughly and unequivocally supported the serotonin theory. Additionally, nine reviews proposed that while serotonin was not the primary or only cause of depression, it was involved in depression in a similar manner described by pharmaceutical industry misinformation. Only one paper came out unequivocally against the chemical imbalance theory.

Most of the papers the current research examined explicitly support the hypothesis that serotonin is involved in depression. Four papers admitted that the connection between serotonin and depression was inconclusive but suggested that serotonin was likely involved in depression.

While all the textbooks acknowledged that the causal relationship between serotonin and depression was an unproven hypothesis, they all provided some support for that unproven hypothesis. In addition, the textbooks all dedicated a disproportionate amount of space to describing serotonin systems and how they may affect depression. The authors conclude:

From our research, it is clear that during the period 1990-2010, there was considerable coverage of and support for the serotonin hypothesis of depression in the psychiatric and psychopharmacological literature. Many of the most highly cited reviews of the etiology endorsed the hypothesis, including some that were entirely devoted to describing research on the serotonin system and those that reviewed the etiology of depression more broadly. Research papers on the serotonin system had very large numbers of citations and most strongly supported the serotonin theory, with a smaller number highlighting inconsistencies in the evidence and adopting a more accurate tone. Textbooks, too, though taking a more nuanced line in places, at other points presented unequivocal support for the theory.”


Ang B., Horowitz M. & Moncrieff J., Is the chemical imbalance an ‘urban legend’? An exploration of the status of the serotonin theory of depression in the academic literature, SSM – Mental Health (2022), DOI: https://doi.org/10.1016/j.ssmmh.2022.100098.(Link)

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