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Chapter 1: What evidence challenges the chemical imbalance theory of depression?
There is no evidence that you have a chemical imbalance in your brain if you are depressed. So therefore, there's no evidence that that antidepressant you're being offered is going to correct that. They haven't asked that question about what antidepressants might be doing by just messing about with our normal brain chemistry.
If you subscribe to this idea that you have a brain chemical imbalance, you actually do worse. You have worse outcomes. The psychiatric profession really seemed to me to just want to shut down the debate. They didn't want people to get an inkling that actually depression has not been proven to be a biological condition.
Chapter 2: How prevalent is antidepressant use in society?
How many people in our society are on these drugs?
So it's something like 8.7 million people in England who take them.
In England?
In England.
So one out of five people of the adult population is on antidepressants.
Almost one out of five are taking antidepressants, which is absolutely staggering, isn't it?
Joanna Moncrief, welcome to Trigonometry.
Thank you for having me.
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Chapter 3: What are the historical misconceptions about depression?
Oh, it's great to have you on. You're one of the people who was instrumental in challenging what is the effective consensus on depression, the idea of it being that it's the product of a chemical imbalance, which is something that was, I think it's fair to say, effectively debunked in the last couple of years. So what is depression and why do we have this false idea of it?
Well, I hope I've debunked that idea, but I think it's actually still quite prevalent. You can still find it on websites and things like that, that depression is caused by lack of serotonin or whatever. So we've had this idea since the 1990s that depression is caused by an abnormality, an imbalance of brain chemicals.
Before that, people used to think of depression as a reaction to bad circumstances, you know, unemployment, divorce, child abuse, childhood trauma. And they saw it as an understandable reaction. Of course, there would be variations between different people. Some people would react more strongly to being made redundant than others. But fundamentally, it was an understandable human reaction.
And then in the 1990s, The pharmaceutical industry released a new range of antidepressant drugs. They wanted to persuade people to take these drugs rather than the old benzodiazepines, which were prescribed for anxiety and which had got this really bad reputation because they caused quite severe dependency problems.
Chapter 4: What does the latest research say about serotonin and depression?
And so to distinguish these new antidepressants from the old benzodiazepines, they persuaded people. They put out this idea, basically, that depression is a medical disorder that is caused by an abnormality in the brain, specifically a deficiency of serotonin, which their new drugs happen to be able to put right.
So that's where the idea comes from, this idea that depression is this medical condition. But it was superimposed onto people's underlying sort of intuition about what depression was, which was quite different.
And the sort of undercurrent on what you're saying is this was a for-profit motivation that caused this to happen.
Yes, yes. I mean, that idea that depression was caused by a chemical imbalance, an abnormality or deficiency of brain neurotransmitters was around. It was first proposed by psychiatrists and researchers working in the 1960s. Again, in the context of developing drugs for emotional problems. But it wasn't sort of widely accepted, certainly among the general public.
Chapter 5: How do SSRIs work and what are their effects?
And so it was the 1990s when the pharmaceutical industry got involved and conducted these very thorough promotional campaigns that really spread this idea. And yes, of course, they did it in order to sell more drugs.
And what does the evidence show about this? Is there any evidence to support the chemical imbalance theory? And if there isn't, what is the evidence telling us about what depression is and where it comes from?
So I did a big review of the evidence, which was published in 2022. And I wrote my book because of the reaction we got to publishing that paper. the astonishment of lots of members of the public and the media that actually there wasn't good evidence for this theory and pushback from the psychiatric profession itself.
And what we did was we got together all the evidence from different areas of research that have tried to look at whether there are links between serotonin and depression. Now, there are thousands of studies
Chapter 6: What are the potential side effects of long-term antidepressant use?
And so what we did was we got together reviews of the studies in all the different areas. Now, some of those studies find evidence of a link between serotonin and depression, show that serotonin is a bit lower in people with depression compared to people without depression.
Some of the studies don't find any difference, and some of the studies show that serotonin is a bit higher in people with depression compared to people without. So overall, when you put all the results together, there's no consistent evidence of an abnormality either way.
And we're talking about the drugs and the medication. I presume we're talking about what is known as SSRIs. So if you could explain what they are and how they work or how they're meant to work and what the truth is.
Yeah, yeah. So SSRI stands for Selective Serotonin Reuptake Inhibitor. And they were a range of drugs that started to be introduced in the 1990s, or actually late 1980s. The first one was Prozac, and the generic name is fluoxetine. And they've been the most widely used antidepressants since then. although some sort of similar drugs have been introduced over the last 20 years.
Now, SSRIs work by inhibiting the transporter protein that takes serotonin out of the gap between the nerve cells where it has its action. where it transports the electrical signal from one nerve cell to another. So the SSRI drugs inhibit the protein that takes the serotonin out of that space.
And therefore the theory is that the serotonin will stay in that space for longer and therefore its activity will be enhanced. That's the theory. We don't really understand what they're actually doing in practice. They probably are having, you know, enhanced serotonin activity temporarily.
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Chapter 7: How should individuals approach coming off antidepressants?
But actually, some of the evidence that we looked at in our review, and this was a surprise, it wasn't something that we set out expecting at all, but some of the evidence we came across suggested that people who are on long-term antidepressants actually may have lower serotonin activity rather than higher activity.
But I think at this point, it's probably important to clarify that the evidence that serotonin has any impact on mood is very, very slim. It's basically the evidence that we looked at that tests whether serotonin levels are different in people with depression or without depression.
And there have been experiments looking at whether serotonin is involved in people's cognitive functioning as well, and animal studies as well, looking at that sort of thing. That has not found consistent findings. There's also research looking at whether serotonin is involved in sleep and appetite. Again, there are no really consistent findings coming out of that body of research.
The only thing, the only area of our functioning where it seems that there's fairly consistent evidence that serotonin has an effect is sexual functioning, and it's bad for it. The more serotonin you have, the less likely you are to want sex or for your sexual organs and everything to work properly.
And that's something that I really wanted to talk about because...
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Chapter 8: What are the implications of identifying with mental health issues?
We don't talk enough about the side effects of these types of medication. And you look at the stats of the amount of people who are on them, particularly in the US and the UK and in Northern Europe and Scandinavia. I mean, one word to describe it is frightening, really.
Yeah, yeah, yeah.
Can you give us those numbers, John? How many people in our society are on these drugs?
So it's something like 8.7 million people in England who take them.
In England?
In England. And that works out as something between 15 and 17% of the adult population.
So one out of five people of the adult population is on antidepressants.
Almost one out of five are taking antidepressants, which is absolutely staggering, isn't it? And, you know, if they were just sugar pills, I think there would still be some problems, but obviously not sort of major physical problems. But they're not just, you know, they're not inert. They are drugs. They do do something.
It's not clear that they do anything much to your mood, but they do, as we've said, have this impact on sexual functioning because we know that, you know, because they are doing something to the serotonin system. And we know that serotonin is involved in our sex lives.
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