Serotonin: the depression theory dogma

The theory of chemical imbalance was long thought to be the cause of depression, but this is now refuted
12 September 2022

Interview with 

Joanna Moncrieff, University College London


A serotonin molecule


That science is vulnerable to dogma is even more troubling when we consider the very important role it has to play in keeping us physically and mentally healthy. Science underpins the practise of modern medicine. Last month, a paper published by a team at UCL demonstrated that the working theory for the cause of depression, and what has informed the characteristics we look for in antidepressant drugs, did not stand up to scientific scrutiny. Speaking with James Tytko, Joanna Moncrieff…

Joanna - One theory about the causes of depression that has been very widely promoted has been the idea that depression is caused by abnormally low serotonin concentrations or activity levels in the brain, which could be corrected by these drugs that were thought to increase levels of serotonin. And it is a theory that was told to very many patients about what antidepressants were doing and what the nature of their symptoms consisted of.

James - What are the problems with this theory that you've found?

Joanna - The problems are that the evidence showing any abnormalities of serotonin in people with depression is weak, inconsistent, and really just basically doesn't stack up. All the different main areas that have tried to in some way gauge what's happening in the serotonin system, in people with depression, and compare it to what's happening in people without depression. There was no convincing evidence from any of those areas of research that there was any between serotonin and depression and certainly no evidence that people with depression had abnormally low serotonin levels.

James - So if we take this chemical imbalance theory of depression as something that's unhelpful, why do you think it's persisted for so many years? Why has it taken until you and your team of researchers to start to question this theory?

Joanna - The theory was established in the minds of people by very well funded, very widespread promotional campaigns run by the pharmaceutical industry, starting in the 1990s and lasting for most of a couple of decades. So that's how it became really well established. Why it persisted is a good question because many leading psychiatrists and researchers have known for some time that actually the evidence for links between serotonin and depression was not convincing or consistent. And yet no one has informed the general public until now, until the media coverage of our recently published paper. And I think that is because many psychiatrists, even though they know that the evidence for serotonin is not strong, really want to believe that the drugs that they prescribe work in a clever and sophisticated way by targeting some underlying biological abnormality. And they don't want to think about their drugs as drugs that change our normal mental states, because that is a bit worrying and would probably make people less likely to take them.

James - There are of course, a lot of interested parties in this scenario, not least the people suffering from depression, but you've mentioned the drug companies as well. What's it been like to be a scientist going up against the mainstream like this? Have you come under pressure? What has the experience been like personally, if I may?

Joanna - Some of my colleagues and many other psychiatrists that most of whom I know by reputation, if I don't know them personally, have clearly been outragedb that I have raised questions about the action of antidepressants and also really that I have suggested that depression might not be due to a specific biological abnormality and that it might be time to think about depression in a different way.

James - Despite the fact that as you mentioned, a lot of them probably have known and would agree with you.

Joanna - Even though the majority of people have said, 'of course we knew that the research on serotonin didn't stack up, of course we knew the low serotonin theory was much too simple. It's much more complex than that.' Despite that, most people want ordinary people to carry on believing that, even though there's no evidence to support the theory that depression is due to low serotonin, it must be due to some sort of other biological abnormality and antidepressants must work in that way. And I think they really deeply don't want people to realize that there are other ways of thinking about depression and other ways of thinking about what antidepressants might be doing.

James - I suppose, is this a story of victory for science over dogma? Or do you feel a bit pessimistic about the role of science in reaching this conclusion or the journey to getting here? How have you felt as a scientist about that process?

Joanna - I mean, I've been making the same points about antidepressants essentially for many years now. Clearly the surprise that greeted the publication of our paper shows that I hadn't got through to many people because most people were still completely convinced that depression had been convincingly demonstrated to be due to a chemical imbalance. So I'm really pleased that the message has got out to more people. And I hope that it will encourage people to question and to be more skeptical. The backlash that I've got from colleagues and from other people in the profession and also in the media makes me very worried about the current state of science. It makes me worried that there are some people who really feel that it is okay to shut down debate. It is okay to characterize a perfectly logical, plausible and well supported opinion as being beyond the pale and something that someone shouldn't be allowed to say. And I think that's a worrying situation. I really hope that the message does get out to more people, because I think it's incredibly important that people are able to make properly informed decisions about the things that they do to their body. And if people don't have information about the sort of drugs that antidepressants are, the fact that they are drugs that change our normal brain chemistry, the fact that drugs that change brain chemistry may have detrimental long term effects. If people don't have all that information, they are not able to make properly informed decisions about whether or not to take antidepressants.


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