The Chemical Imbalance Myth

Photo: Amir Moharrami / Unsplash

For decades, if you went to your GP feeling down or depressed, you were probably told some version of the same thing: that your brain had a chemical imbalance, probably involving serotonin, and that medication would correct it. It was a convenient explanation that seemed to make sense, and so it stuck. By the early 2000s it had moved from clinical shorthand into everyday language, the kind of thing that people took as a given when discussing mental health.

But we now know that the evidence never really supported it.

What the Evidence Actually Shows

In 2022, Professor Joanna Moncrieff and colleagues at University College London published a systematic umbrella review in Molecular Psychiatry, a comprehensive analysis drawing together decades of research on serotonin and depression.¹ Their conclusion was unambiguous: there is no consistent evidence that depression is caused by low serotonin levels or reduced serotonin activity. Studies examining serotonin in the blood, in the brain, and via the genes that regulate it have failed to produce findings that support the hypothesis. The review has been downloaded more than a million times. Notably, the RACGP's own clinical news platform published the findings directly, with Moncrieff as author, in the same month the paper appeared.³

The response from the research community has been significant. In 2023, thirty-six senior researchers published a formal critique in the same journal, raising methodological objections.² Peer critique of this kind is exactly how science should work. What those thirty-six researchers could not do, however, was effectively refute the original claim. Even those most critical largely concede that the simple chemical imbalance narrative was never well-supported by the evidence. The debate concerns the finer details of serotonin research, not whether the explanation offered to patients for thirty years was accurate.

It was not.

The debate concerns the finer details of serotonin research, not whether the explanation offered to patients for thirty years was accurate.

How the Story Shaped the Treatment

This matters for a specific reason. The explanation shaped the treatment. If depression is a chemical problem, the obvious response is a chemical fix. Antidepressant prescriptions have risen sharply across Australia over the past three decades, to the point where around one in seven Australians now takes them, with 92% of those scripts written by GPs.⁵ That figure sits uncomfortably alongside the fact that the foundational rationale for that level of prescribing has not held up to scrutiny.

The clinical landscape is beginning to shift. In November 2025, the RACGP added a new section to its First Do No Harm guide addressing long-term antidepressant use.⁴ The guide notes that most clinical guidelines recommend antidepressants for only six to twelve months for an episode of anxiety or depression, while the average duration of use in Australia is four years. It directs GPs toward careful review, shared decision-making, and non-pharmacological management wherever possible. It is not a repudiation of prescribing. It is, however, a formal acknowledgment that the default has been running well ahead of the evidence.

Naming the Gap

The work of organisations like the Not Broken Project, co-founded by Professor Jon Jureidini and Alfred Health psychiatrist Dr Paul Denborough, is oriented precisely toward this gap: naming what the evidence shows, and advocating for better non-pharmaceutical support for people experiencing grief, loneliness, sadness, and distress linked to life circumstances.⁶ These are not edge cases. They describe a significant proportion of the people who present to GPs and to counsellors each week.

Much of what gets labelled depression is, on any honest account, a human response to human experience. Grief after loss. Loneliness following a relationship breakdown or a significant life change. The slow accumulation of stress, disconnection, or meaninglessness that builds when life has gone in a direction that does not fit who you are. A workplace devoid of limits or humanity. A life lived discordant to your values. And so on, and on.

None of that is a malfunction. Framing it as one is not only scientifically unsupported; it can actively discourage people from the kinds of help that would actually serve them.

What Counselling and Psychotherapy Actually Do

Counselling and psychotherapy work with the actual content of a person's distress. They help you make sense of what has happened, understand the patterns that keep you stuck, rebuild connection with yourself and others, and find your way toward a life that feels liveable. For many people experiencing what gets called depression, this is the real treatment.

None of this means medication is never appropriate. There are people for whom it plays a genuine and useful role, often for a specific period, and in conjunction with therapy, and nothing here is intended as advice about any individual situation. My assessment is that the story used to justify widespread, default pharmaceutical treatment of emotional distress was not built on solid evidence, and that the people most likely to have been ill-served by it are those whose suffering had its roots in circumstances that no pill was ever going to change. What follows from that is equally important: greater investment in talking therapies, and broader public understanding of what counsellors and psychotherapists actually do, are not optional additions to a mental health system built around medication. (And we've not mentioned how much cheaper an antidepressant is than effective therapy.) For a significant proportion of people, they are the more appropriate first response.

If that sounds like where you are, there is help that is designed for exactly that.

References

1. Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry. 2022;28:3243–3256. https://doi.org/10.1038/s41380-022-01661-0
2. Bartova L, Lanzenberger R, Rujescu D, et al. Reply to: “The serotonin theory of depression: a systematic umbrella review of the evidence.” Mol Psychiatry. 2023;28:3153–3154. https://doi.org/10.1038/s41380-023-02093-0
3. Moncrieff J, Horowitz M. Depression probably not caused by chemical imbalance: Study. newsGP (RACGP). 22 July 2022. racgp.org.au
4. RACGP. Long-term use of antidepressants without careful review. First Do No Harm guide. November 2025. racgp.org.au
5. Australian Institute of Health and Welfare. Mental health services in Australia: medications. 2024–25. aihw.gov.au
6. Not Broken Project. notbrokenproject.com.au

Does any of this resonate with you?

If your distress has roots in life circumstances, there is help designed for exactly that. I'd be glad to talk.

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