Transcription of a discussion held on the Today programme, 24 January 2025:
Presenter, Amol Rajan:
What does the evidence suggest about the link between serotonin, a chemical in our brains and depression? And what does that imply for antidepressants, which target serotonin? This is the subject of a new book by Dr Joanna Moncrieff. She’s professor at University College London, practicing psychiatrist and author of Chemically Imbalanced, the Making and Unmaking of the Serotonin Myth.
A brief survey of online coverage will show that this subject is hugely contentious. It really does seem to give rise to very heated exchanges and something about it strikes at the very heart of people’s sense of self. But it’s also very timely because in recent years, the use of antidepressants has risen sharply in this country, including among young people.
In a few minutes, we’ll speak to Professor Simon Wessely, who’s Regius Professor of Psychiatry at King’s College London. But first, here is Joanna Moncrieff. When I spoke to her, I began by asking her to put forward her argument.
Professor Joanna Moncrieff:
What I wanted to get across is that the idea that depression is caused by a deficiency of serotonin has not been established because many people had come to believe that it had been. And indeed, I think the public have basically been misled about this. And I became aware when we published our paper on the serotonin theory of depression, that there was still a section of the psychiatric community out there who didn’t really want people to know that it was the case that this hadn’t been established and wanted people to carry on believing that we have found the biological cause of depression when in fact we haven’t.
Presenter, Amol Rajan:
Right. And there has been a very considerable reaction from that community, which we’ll get to. But just to be clear, if the drivers of depression aren’t chemical, what are they? Well, I think we need to approach depression in a different way.
Professor Joanna Moncrieff:
I think we need to understand it differently. So instead of looking for a cause as if it was a mechanical event, I think we need to see it as a meaningful reaction to people’s life circumstances, which is coloured and shaped by the things that have happened to them in the past. You know, the reason why I think it’s important for people to know that the serotonin theory of depression is a theory and not established by evidence, is because the idea of taking a drug to rectify an underlying abnormality that you have, of course, makes sense, doesn’t it? As long as the adverse effects aren’t too terrible, you might be prepared to put up with them, because it would be normalising your biology in some way.
But if we have no evidence that there is an underlying abnormality of serotonin or anything else, then we’re left with the fact that what you’re taking is a drug that is actually changing your normal brain chemistry. And we don’t know the full consequences of doing that. And generally, it’s not a good idea to take something that messes about with your brain chemistry unless we have really good research that conclusively shows that this is safe. And I would say that we don’t have that.
Presenter, Amol Rajan:
No one really, I mean, maybe the public have some kind of slightly stereotypical views of depression, but actually in the industry, you know, leading consultant psychiatrists haven’t thought for a very long time that chemical imbalance is the only issue. So Dr Michael Bloomfield, who you all know well, consultant psychiatrist at UCL says, and I quote, “I don’t think I’ve met any serious scientists or psychiatrists who think that all causes of depression are caused by a simple chemical imbalance in serotonin”. Professor David Curtis, also at UCL, “the notion of depression being due to a chemical imbalance is outmoded”. So in a sense, isn’t the thing that you’re taking down a view of depression and serotonin, which actually we kind of decided quite a long time ago, maybe 20 odd years ago, was outdated?
Professor Joanna Moncrieff:
If psychiatrists had decided that, they haven’t been communicating that to the general public. And when a prominent American psychiatrist wrote a blog saying exactly the same thing, no one believes this, no one’s been presenting this, a few years ago, he was inundated with people who said, actually, this is exactly what we’ve been told. And people were, doctors were telling the public that depression was due to a chemical imbalance weeks before we published our paper. People used to think of depression as an emotional reaction to events in people’s lives, as an understandable reaction. And that view was deliberately overridden by a marketing campaign led by the pharmaceutical industry in which the medical profession collaborated, which persuaded people that there was established evidence and that their intuition about the meaning of depression therefore could be overridden, should be rejected.
Presenter, Amol Rajan:
So what’s testable about the case that you’re making? What’s the evidence that you have that shows that you’re right?
Professor Joanna Moncrieff:
Well, I suppose what I’m, what I’m suggesting is that human emotions are not mechanistic things that can be tested in a scientific manner.
Presenter, Amol Rajan:
So you’re saying that your position doesn’t necessarily have evidence because you can’t test for it?
Professor Joanna Moncrieff:
I’m suggesting that trying to understand human feelings and human ideas and thoughts as if they were the same as looking at mechanical processes in the world is not the right way of thinking about them.
Presenter, Amol Rajan:
What’s your view as to whether or not it follows that antidepressants that target serotonin do or don’t work?
Professor Joanna Moncrieff:
The evidence, to my mind, doesn’t provide evidence that they are much better than a placebo. And even the small difference between antidepressants and placebo is explicable by them having amplified placebo effects, i.e. people being able to detect whether they’re on the antidepressant or not.
Presenter, Amol Rajan:
Can I again, just in the spirit of fullness and fairness, say that the argument that antidepressants are essentially, basically a fancy placebo is one that other scientists dispute? And I want to give you a chance to respond to that. So for instance, Andrea Cipriani’s 2018 meta-analysis concluded, and I quote, “all antidepressants were more efficacious than placebo in adults with major depressive disorders”.
Professor Joanna Moncrieff:
I look at that meta-analysis in quite a lot of detail in the book because it was very well done for what it did, and it was very comprehensive. And that meta-analysis, like all the others, showed a very small difference between antidepressants and placebo that, as I say, can easily be explained by amplified placebo effects.
But even assuming there is a small pharmacological effect of antidepressants, we have to then balance that with the negative effect of antidepressants. And I think that these have been underrated. We know that they cause sexual side effects when people take them, that’s not disputed. And there is emerging evidence that in some people, those sexual side effects continue after they’ve stopped taking the antidepressant. Now, that’s a huge thing, especially because more and more young people are taking antidepressants and not enough awareness of that possibility also know that people who are taking antidepressants for several years at a time can have real difficulty getting off them. And again, the withdrawal symptoms can go on for months and years, sometimes after people have stopped taking the antidepressant.
So there are significant side effects or adverse effects to these drugs that need to be factored in to decisions about whether to take them or not.
Presenter, Amol Rajan:
And more and more people are taking them, including, as you say, more and more young people, which is why it’s so good to talk to you about this subject. Joanna Moncrieff, thank you very much indeed for talking to us.
Professor Joanna Moncrieff:
Thank you, Amol.
Presenter, Amol Rajan:
Well, let me just say that the current NHS advice is that research suggests that antidepressants can be helpful for people with moderate or severe depression. And it’s important that you talk to your doctor before you stop taking them rather than doing that suddenly.
If you’re suffering distress, you need support, please do look at bbc.co.uk forward slash action line, where you can find a list of organisations that can help you, you can talk to someone or you can call for free on 0800 066 066. That’s 0800 066 066.
Presenter, Amol Rajan:
Let’s turn now to Professor Sir Simon Wessely, who’s Regius Professor of Psychiatry at King’s College London, past president of the Royal College of Psychiatrists and the Royal Society of Medicine.
Important distinction there, Simon. Good morning, Simon. I just want to give you a chance to respond in the broad terms to what you heard from Joanna Moncrieff, who I know you know well.
Professor Sir Simon Wessely:
[laughs to himself] Yes, I do know Jo well. And we actually wrote a paper about this almost 30 years ago, rather shocking to remember.
I mean, I think you’ve already gone over the principal counter arguments. The serotonin hypothesis is almost as old as me, and is not entirely discredited, because we do think there is some role for neurotransmitters like serotonin in the workings of the brain and the development of mood disorders. But it’s still, you know, it’s not regarded as the be all and end all or the cause of depression and hasn’t been for most of my career.
So I think Jo’s created a bit of a straw man there. And the second bit is that I don’t think anyone in the field thinks this is a solely biological disorder in the way that she said. And no one disputes that it involves a combination of some neurobiology, how the brain works, that that should have some effect on mood is hardly a surprise.
Psychology, our emotions, our early experiences, our social and life and political factors, unemployment, housing, racism, discrimination, all of these are part and parcel of the experience of depression. And I just don’t think anybody in the field, I’ve never met anyone who doesn’t think that’s the case. Sure.
Presenter, Amol Rajan:
But let me just push back in one sense, if I may, Professor Wessely, because Joanna Moncrieff is onto something, isn’t she, when she says that there has been a very sharp rise in antidepressants or usage of it. And if that has overtaken, the rise has overtaken the rise in actual depression, maybe there has, by implication, been too much of a reliance on antidepressants. Is there something in there?
Professor Sir Simon Wessely:
Well, there is certainly evidence the number of prescriptions has been rising steadily for many years now, up to several over 65 million.
But there’s a lot of reasons for that.
The first reason is indeed depression has got more common in the last decade for reasons that are complicated as well. So that’s the first thing.
Second, we prescribe better now because we give prescriptions for shorter periods of time, which makes the numbers go up. And that’s safer because GPs who do the majority prescribing don’t like giving people big stacks of antidepressants or indeed any other drug.
But it is also possible that people are getting antidepressants who don’t need them. That’s correct.
But we also know that we have probably more people who might benefit from them, when we know the epidemiology of depression, who aren’t getting them. So I don’t think we’ve got a cause to panic.
And I’ll probably ask you, what do you think is the right number of antidepressants to prescribe? And I don’t think you would know.
Presenter, Amol Rajan:
Well, I certainly don’t know. Luckily, that’s why.
Professor Sir Simon Wessely:
It’s not about the number of prescriptions. It’s about are the right people taking it for the right indications? There’s evidence that sometimes they’re not. But there’s plenty of other evidence that depression is still being missed. Some people are reluctant to admit to it. And sometimes it’s mixed up with other disorders.
Presenter, Amol Rajan:
Final point, go on.
Professor Sir Simon Wessely:
Yeah, it’s this that what the real thing that has, I think, upset people is to the extrapolation she makes from saying that we don’t know really what depression is all about. That’s true. We don’t know how antidepressants work. Well, the first line of the NHS website says, we don’t know how antidepressants work. So that’s not a secret. But we do know that they are moderately effective.
We’ve known about it for 40 years. And we know what the side effects are. And all of that.
Professor Sir Simon Wessely:
I don’t want people to think that it’s …. [Interrupted by presenter, as time is running short]
Presenter, Amol Rajan:
… unclear or that they should stop taking medication when actually it’s pretty [voice fades and is unclear]. Well, hopefully our caveat has made that clear. We’ve got to leave it there.
Professor Sir Simon Wessely, thank you. Because we’re coming up to the end of the programme .