Experts respond to the Moncrieff review of the chemical imbalance theory – are the conclusions accurate?


Professor Joanna Moncrieff’s recent paper, The serotonin theory of depression: a systemic umbrella review of the evidence, has been extensively discussed in the media since it was published on July 20th in Molecular Psychiatry.

The comprehensive meta-analysis of the six major strands of research on serotonin concluded that there was “no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations.”

“Our view is that 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 unproven abnormalities,” Professor Moncrieff said.

“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.”

Yet in a piece written for The Conversation, published August 2nd, Professor Chris Davey, Head of the Department of Psychiatry at the University of Melbourne and editor-in-chief of the Australian and New Zealand Journal of Psychiatry, raised issues with the review’s conclusions.

Whilst he agreed with basic findings that there is no evidence to support the chemical imbalance theory, he was concerned that their underlying message had been “amplified by the extensive media attention that the article received.”

“Much of the commentary has extrapolated from the study’s finding to suggest it undermines the effectiveness of antidepressants – including by the authors themselves,” Professor Davey wrote.

“This shows a misunderstanding of how medical science works. Medicine is pragmatic [and] has often established that a treatment works well before it has understood how it works.”

He went on to explain that “the first two antidepressant medications, both discovered in the 1950s, were observed to have positive effects on mood as side effects of their hoped-for functions,” and as both drugs increased levels of serotonin, the resulting hypothesis was that low serotonin was the cause of depression.

A ‘replication crisis’ in research coincided with a fresh sales proposition by big pharma to market their newly developed range of SSRIs – Prozac, Zoloft, and Cipramil – to spawn the current misconceptions.

Similarly, Emeritus Professor of Psychiatry, Bioethics and Humanities at SUNY Upstate Medical University, Dr Ronald Pies, was inspired to write a response in this week’s edition of Psychiatric Times, stating that “the Moncrief et al review was hardly news to psychiatrists” and fails to capture “the complexity of serotonergic systems and signalling in the brain.”

“The techniques described in the Moncrieff review were not designed to determine antidepressant efficacy, which is determined by randomized controlled clinical trials,” Dr Pies wrote.

“Thus, no conclusions can be drawn from their review regarding antidepressant efficacy, or the ‘good versus harm’ associated with antidepressant treatment.

“Most importantly, the review by Moncrieff et al does not in any way impugn the overall safety and effectiveness of serotonergic antidepressants in the acute treatment of moderate-to-severe major depression.”