From Psychology Today: “Almost as soon as it was floated in 1965 by Harvard psychiatrist Joseph Schildkraut, the serotonin hypothesis of depression—reduced and simplified by pharma marketing to the ‘chemical imbalance’ theory of depression and anxiety—has been subject to critical research and found wanting.

The poor standing of the hypothesis in the scientific literature, however, barely dented its afterlife in textbooks, across clinical and treatment settings, and on mental health apps and websites. Nor has it dispelled the continued use of the phrase as ‘shorthand’ between doctors and patients and in everyday settings, including for quite different mental states and conditions . . .

Cut to the Present-day

A major new review of the research—the first of its kind exhaustively reviewing the evidence, published today in the journal Molecular Psychiatry— . . . found ‘there is no evidence of a connection between reduced serotonin levels or activity and depression.’

The peer-reviewed umbrella review—representing one of the highest forms of evidence in scientific research—was extrapolated from meta-analyses and systematic reviews on depression and serotonin levels, receptors, and transporters involving tens of thousands of participants.

Although ‘the serotonin hypothesis of depression is still influential,’ Moncrieff and coauthors noted, citing widely adopted textbooks published as recently as 2020 and surveys indicating that ’85-90 percent of the public believes that depression is caused by low serotonin or a chemical imbalance,’ the primary research indicates there is ‘no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations.’

. . . Moncrieff explained in the press release:

‘Patients should not be told that depression is caused by low serotonin or by a chemical imbalance and they should not be led to believe that antidepressants work by targeting these hypothetical and unproven abnormalities. In particular, the idea that antidepressants work in the same way as insulin for diabetes is completely misleading. We do not understand what antidepressants are doing to the brain exactly, and giving people this sort of misinformation prevents them from making an informed decision about whether to take antidepressants or not.’

Invited to extrapolate the review’s findings for Psychology Today, Moncrieff added:

‘Antidepressant use has reached epidemic proportions across the world and is still rising, especially among young people. Many people who take them suffer side effects and withdrawal problems that can be really severe and debilitating. A major driver of this situation is the false belief that depression is due to a chemical imbalance. It is high time to inform the public that this belief is not grounded in science.’”



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