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The serotonin hypothesis of depression: both long discarded and still supported?

Molecular Psychiatry volume 28, pages 3160–3163 (2023)Cite this article

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The Original Article was published on 20 July 2022

We thank the authors of all the letters for their interest in our paper [1]. The reason our paper is important is that the pharmaceutical industry, along with many doctors and academics, have been telling the public for decades that depression is caused by a neurochemical abnormality in order to justify the use of antidepressants, and to overcome some people’s reluctance to use mood-modifying medicines [2, 3]. Our paper exposed this claim as untrue. The main areas of research do not provide support for the most well-known neurochemical hypothesis, the serotonin theory of depression—the idea that depression is caused by low levels or low activity of serotonin.

There are always further studies that can be presented to support the serotonin theory, and research on other possible biological mechanisms, which may or may not involve serotonin. However, we synthesised all existing studies from the main areas of research on serotonin and depression. The onus is on others to present a convincing case based on other types of research or alternative hypotheses, not on us to disprove every speculation.

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Author information

Authors and Affiliations

  1. Division of Psychiatry, University College London, London, UK

    Joanna Moncrieff & Mark A. Horowitz

  2. Research and Development Department, Research and Development Department, North East London NHS Foundation Trust (NELFT), Rainham, UK

    Joanna Moncrieff & Mark A. Horowitz

  3. NIHR Mental Health Policy Research Unit, Health Service and Population Research Department, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK

    Ruth E. Cooper

  4. Praevmedic, Zürich, Switzerland

    Tom Stockmann

  5. Department of Applied Psychology, Zurich University of Applied Sciences, Zurich, Switzerland

    Simone Amendola & Michael P. Hengartner

  6. University Clinic of Psychiatry Psychotherapy and Psychosomatics, Paracelsus Medical University Salzburg, Salzburg, Austria

    Martin Plöderl

Authors
  1. Joanna Moncrieff
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  2. Ruth E. Cooper
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  3. Tom Stockmann
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  4. Simone Amendola
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  5. Michael P. Hengartner
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  7. Mark A. Horowitz
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Contributions

JM wrote the first draft of the manuscript. All other authors substantially contributed to edits and revisions of the manuscript. All authors have approved the final version of the manuscript.

Corresponding author

Correspondence to Joanna Moncrieff.

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Competing interests

JM receives royalties for books about psychiatric drugs, and is a co-applicant on the REDUCE trial, funded by the National Institute of Health Research, evaluating digital support for patients stopping long-term antidepressant treatment. She is co-chairperson of the Critical Psychiatry Network (an informal group of psychiatrists) and a board member of the unfunded organisation, the Council for Evidence-based Psychiatry. Both are unpaid positions. MAH reports being a co-founder of Outro Health which provides digital support for patients in Canada and the US to help stop long-term antidepressant treatment using gradual, hyperbolic tapering. MAH and JM are both co-applicants on the RELEASE trial in Australia evaluating hyperbolic tapering of antidepressants against tapering as usual. He is also an Associate of the International Institute for Psychiatric Drug Withdrawal (IIPDW) and a member of the Critical Psychiatry Network. RC is a Board Member of the International Institute for Psychiatric Drug Withdrawal (IIPDW), this is an unpaid position. TS is co-chairperson of the CPN (an unpaid position). MPH receives royalties from Palgrave Macmillan for a book about antidepressants. Other authors report no potential conflicts of interest.

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Moncrieff, J., Cooper, R.E., Stockmann, T. et al. The serotonin hypothesis of depression: both long discarded and still supported?. Mol Psychiatry 28, 3160–3163 (2023). https://doi.org/10.1038/s41380-023-02094-z

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