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- [00:01]
Podcast Host
This episode is brought to you by Google Chrome. You think you know a browser, but Gemini and Chrome, that's new. It can help you with practically anything on the web, like restoring a vintage motorcycle from a 50 page restoration block. Or finally break down that long article you've had open for weeks. Gemini and Chrome is here for it, ready to make anything online make sense. There's no place like Chrome. Check responses set up, required compatibility and availability various 18 plus.
- [00:28]
Joanna Moncrieff
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.
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Interviewer
How many people in our society are on these drugs?
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Joanna Moncrieff
So it's something like 8.7 million people in England who take them.
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Interviewer
In England. In England, one out of five people of the adult population is on antidepressants.
- [01:19]
Joanna Moncrieff
Almost one out of five are taking antidepressants, which is absolutely staggering, isn't it?
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Interviewer
Joanna Moncrief, welcome to trigonometry.
- [01:27]
Joanna Moncrieff
Thank you for having me.
- [01:28]
Interviewer
Oh, it's great to have you on. You're one of the people who was instrumental in challenging the. What is the effect of consensus on depression? The idea of it being that it's a, 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?
- [01:54]
Joanna Moncrieff
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, you know, being made redundant than others. But that fundamentally it was an understandable human reaction. And then in the 1990s, the pharmaceutical industry released their 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. 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.
- [03:41]
Interviewer
And the sort of undercurrent on what you're saying is this was a for profit motivation that caused this to happen?
- [03:49]
Joanna Moncrieff
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. 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.
- [04:35]
Interviewer
And what does the evidence show about this? Is there any evidence to support the chemical imbalance theory? And if it's, if there isn't, what is the evidence telling us about what depression is and where it comes from?
- [04:44]
Joanna Moncrieff
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, you know, 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. 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.
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Co-Host/Interviewer
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.
- [06:11]
Joanna Moncrieff
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. The generic name is Fluoxetine, and they've been the most widely used antidepressant 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. 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, 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 depression, 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.
- [08:56]
Co-Host/Interviewer
And that's something that I really wanted to talk about because 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 U.S. and the U.K. and in northern Europe and Scandinavia. I mean, one word to describe it is frightening. Really?
- [09:17]
Joanna Moncrieff
Yeah, yeah, yeah, yeah.
- [09:18]
Interviewer
I mean, can you give us those numbers, Joanna? How many people in our society are on these drugs?
- [09:23]
Joanna Moncrieff
So it's something like 8.7 million people in England who take them.
- [09:28]
Co-Host/Interviewer
In England?
- [09:28]
Joanna Moncrieff
In England. And that works out as something between 15 and 17% of the adult population.
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Interviewer
One out of five people of the adult population is on anti depression.
- [09:37]
Joanna Moncrieff
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. We're not, 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, in our sex lives.
- [10:10]
Interviewer
You say they don't do anything for you mood. My understanding, look, I've never taken antidepressants, so I don't know, but I. Even if they don't address the chemical imbalance, I've always kind of thought, well, if you give someone drugs, they're probably going to feel better for a while just because they're on drugs. It's like if I have a glass of wine tonight, I'm gonna feel a little bit more relaxed. Or what is, are they not having any effect like that?
- [10:34]
Joanna Moncrieff
So that's a really good point and I've been writing about this for a long time. So what you've described, the idea that a drug will have some sort of impact on how you're feeling is what I've called the drug centered model of drug action. So that's one way of understanding how drugs might affect our moods and our feelings. And that contrasts with the mainstream view that what these drugs are doing is targeting some underlying abnormality. So your idea that drugs that enter the brain are going to change our normal feeling states is correct. If we think of something like alcohol, you can be feeling very depressed, go out and have a shed load to drink, and temporarily you might well feel better again. Obviously it's not solving anything in the moment, except in the moment. So antidepressants, at least, probably most classes of antidepressants have some emotional numbing effect. We know that because of lots of people describing that. I think it's, you know, we've probably come across people who are taking antidepressants and describe how, you know, they can't cry and they don't feel sort of joy or excitement anymore. You know, they might not feel as intensely sad as they were, but everything's, you know, a bit flat.
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Co-Host/Interviewer
And
- [12:01]
Joanna Moncrieff
so antidepressants have that effect. But whether that effect is actually beneficial or not is questionable. And I say that because the trials of antidepressants that have compared them with placebos, that is inactive dummy tablets, really don't show very much difference. Even despite that emotional numbing effect. The difference between taking an antidepressant and a placebo in these trials is really small. It's 2 points on a 52 point typical 52 point depression rating scale.
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Interviewer
So it numbs your feeling a little bit, which is not super impactful.
- [12:46]
Joanna Moncrieff
Yeah.
- [12:47]
Interviewer
So come back with me then to the question of, well, if depression is not a chemical imbalance and in fact, even if there were different levels of serotonin, it's kind of like saying, well, people who are depressed don't smile as much, therefore smiling is an antidepressant. Which, you know, I don't know if there's a lot of evidence for that, but do we know what actually does cause depression?
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Joanna Moncrieff
So the trouble with that question is it sort of presupposes that depression is a thing like lung cancer and we can, you know, we can target a particular cause. And I would suggest that that's the wrong way to think about it. I think depression is a personal state, you know, it's a type of emotion, a type of feeling. And after persistent sadness. So yes, persistent sadness, you know, loss of interest, loss of motivation, social withdrawal, these are all the common features and that we recognize that, you know, that are quite common and we may have experienced ourself or seen in other people around us. And by and large, those reactions and feelings are caused by things that are happening in our lives. They are an understandable reaction to events like relationship difficulties or loss or change or struggling at work, all those sorts of things. And the causes will be different in each person. The reason I don't like this way that we talk about depression as if it is the same as having, you know, cancer, is that it implies that it's the same thing in every person. And therefore we can treat each person with depression in the same way. And of course that's what we do. We give them antidepressants and cognitive behavioral therapy, which may be useful for some people. I'm not doubting that, but I think we ought to see depression as a reaction of an individual. And then, you know, the next logical step is to ask, well, why has this individual got into this state at this particular time? What's going on in their lives and what sort of help do they need? And then you realize that each individual who has depression is going to need different sort of help and support.
- [15:07]
Interviewer
That makes sense. As always, I'm racking my brain for counter arguments just to stress test what you're saying. A couple of things that I think where you might say, well, hold on, isn't this an imbalance or some kind of almost medical thing, or at least chemical thing, is something like postnatal depression where we know it's quite a common thing when actually something generally quite wonderful has happened. Right. A woman gives birth, has a child and then she is depressed. Is that different to or is. Well, what's your take on that?
- [15:40]
Joanna Moncrieff
Well, the first thing to say is. So one of the arguments that was made when we published our paper on serotonin and depression was that there are lots of different types of depression. So, you know, you can't say that there's no biological cause of depression. I would change that that round and say, well, there isn't any evidence of a biological cause in any sort of subtype of depression. That may be because people haven't done enough research into the different subtypes. But as it is at the moment, we can't say that postnatal depression is different, that we found some sort of biological cause for that. And I would say that actually for most people, postnatal depression, although it seems a bit counterintuitive, is often a response to a major change in one's circumstances. Having a baby, having major responsibility at a time when, yes, one's hormones are flying around and probably not completely stabilized as well. So. But I don't think it's necessarily completely different from other cases.
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Interviewer
Well, the hormones thing is kind of my point, because I take your point about it's a major change, but if you put £10 million in my bank account, that is a major change. I'm very unlikely to Develop post millionaire depression or whatever you might call. Do you see what I mean? So that's one. And the other one I was gonna ask you is what about is there such a thing? Cause I guess I've always been very sympathetic to the argument you're making. As someone who was. I don't even like to say I had depression. I think it makes it sound like you had a thing. I definitely was depressed at one point in my life, but it was a reaction to the circumstances and also partly to my own behavior. Right. I know how to become depressed. If I stay indoors, don't exercise, don't eat well, drink alcohol, you know, don't talk to human beings for a couple of weeks, I guarantee you I'm going to be depressed at the end of that. Right, but the counter argument that people have always wheeled out was yeah, yeah, but you don't, you don't have clinical depression. Clinical depression is a totally different thing. Is there such a thing as clinical depression?
- [17:49]
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- [17:54]
Interviewer
And these days the biggest red flag
- [17:56]
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- [18:27]
Interviewer
That's a pretty big update.
- [18:28]
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- [18:57]
Joanna Moncrieff
So again, there's no evidence that there is a specific subgroup of people with depression who have something that is biological and medical and different from the sort of depression that we might all experience. We've been told for many, many years now, haven't we, that there is, you know, a different thing called clinical Depression, which is a proper medical condition. So, you know, most people are signed up to that. If you're told something, you know, enough times, you think it must be true, especially if you're told by experts. But actually, there's no evidence. You know, all these studies on serotonin and depression were done with people with, you know, clinical depression. They'd had depression diagnosed by their doctors, which is all that we really mean by clinical depression. And we're still not finding evidence for, you know, biological abnormalities in them. But also, I think. I think it's important to realize that there's no sort of secret ingredient to the diagnosis of depression. You know, someone who's feeling unhappy and struggling with life, goes to their doctor, says, I'm, you know, I'm unhappy and I'm struggling. And the doctor, you know, on the day makes a judgment about whether or not they think they should be treated with antidepressants or not. You know, should we consider this to be a sort of medical case that we're going to give medical treatment to and that, you know, that decision isn't made by, you know, rigidly following some very precise.
- [20:27]
Interviewer
There's no antibody in the bloodstream that you do.
- [20:30]
Joanna Moncrieff
No. And there's certainly no objective physical tests that can tell the doctor. And so it depends a lot on the doctor. You see, you know, whether they've seen a pharmaceutical industry rep that lunchtime before they saw you, their sort of outlook on life, how they understand emotions, the training they've had, and it depends on how the individual patient presents as well. So some people, you know, come to their doctor convinced that they have a medical problem that they need, you know, an antidepressant or some sort of chemical solution. And some people come, you know, much more uncertain, not really knowing what the right, you know, what the right way to interpret this is. And that will influence whether the doctor says, you know, you have clinical depression or not as well.
- [21:17]
Co-Host/Interviewer
I'm putting myself in the shoes of a GP who's. Who's got this patient coming to them. They say they're depressed because, let's say, a bereavement, their child has died. I feel that I have to do something. I can't send this person away. I can say, oh, you're going to get counseling or some type of CBT on the NHS, but the waiting list is 18 months. Probably get even longer than that. What am I going to do? I'm just going to let this person go? No, I need to be seen to be doing something. Because if they do something Extreme, then it's going to come back to me. So in order to cover myself and to be seen to be doing something, I'm going to prescribe antidepressants.
- [21:56]
Sponsor Voice
Isn't that how it would work?
- [21:58]
Joanna Moncrieff
I think it absolutely does work like that. And I think that's one of the main reasons why we have such huge rates of prescribing.
- [22:07]
Co-Host/Interviewer
And,
- [22:09]
Joanna Moncrieff
you know, yes, understandably, gps want to feel, you know, want to be able to offer people something waits for therapy were very long or there was no therapy available at all for, you know, many decades here. We do now, though, have a national therapy service which has much, you know, waiting lists of a few weeks. So that's not quite so bad. But I think, yeah, I think that's a really good point. I think, you know, and I think one of the problems is that because, because we've medicalized depression, because we've told people to go and see their doctors, then it just gets confirmed. Because, you know, if you have a hammer, everything looks like a nail, don't you? And what do doctors have? They have a prescription pad and a diagnostic book. So, you know, they tell you, yes, you've got this condition and this is the treatment, this, this drug.
- [22:58]
Co-Host/Interviewer
Absolutely. And to me, one of the great tragedies about when we talk about depression or any type of mental health condition is because we don't know a lot about it, if we're being honest, because that does seem to be the central theme of the conversation is like, look, we don't actually know. So a lot of the time the treatment or the procedures are actually do more harm than good.
- [23:20]
Joanna Moncrieff
Yeah, absolutely, absolutely. I mean, this is one of the main messages I would like to get across to people. 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. But we do know that antidepressants are, you know, real drugs that enter the brain and change the normal state of our brain chemistry and that, you know, and that can have harmful consequences. That's not necessarily a, you know, harmless thing to do. We should be worried about messing about with our brain chemistry and we haven't, because the psychiatric profession and all the psychiatric research establishment has been so focused on this wrong idea that antidepressants target some underlying imbalance or some other sort of underlying dysfunction of the brain. They haven't looked, they haven't asked that question about what antidepressants might be doing by just messing about with our normal brain chemistry? What are the consequences if you take these drugs for months and years at a time, as many people do? There's really not very good research on that. There are, as we mentioned earlier, some suggestions coming out that actually these drugs can be very damaging to people's sexual functioning, people's emotional life, that they can cause severe withdrawal symptoms. But all these things have actually come out because people have been reporting them, not because people were doing, you know, had set up systematic research studies to investigate the consequences of use in the first place.
- [25:03]
Co-Host/Interviewer
And to me, it derives as well from the fact that we just, if we're being honest, we don't really understand the brain. I mean, you look at the other organs and you go, well, you know, we understand the kidney pretty well. The heart. I mean, the heart is basically a muscle or the liver or whatever else. But even if you talk to one of the most eminent neurologists of the day and you ask them a question about the brain, I'm sure a lot of them would go, look, we don't know about X, we don't know about Y, we don't know about Z. So we, in absence of all this knowledge, we're just thinking of these techniques of how to help people.
- [25:36]
Joanna Moncrieff
Yeah, yeah. I mean, I think we've got a wrong impression that we know more about the brain than we do. And that's partly because of the way that a lot of neuroscience findings are presented and reported. You know, so we're always seeing articles, aren't we? Like, you know, you can boost your dopamine by doing this, and, you know, if you have more dopamine, you'll. You'll, you know, be more active or a better athlete or something like that. And if you. If you lack serotonin, then you. Then you're, you know, not only just not as happy, but. But, you know, socially dysfunctional or something like that. So, you know, these headlines get put out there all the time. So people have the impression that we know more about the brain than we do. And I would agree we don't know very much about it. For example, we know we've identified a lot of the different chemicals that are active in the brain, but we understand very little about what each of them do.
- [26:35]
Co-Host/Interviewer
And why is that?
- [26:38]
Joanna Moncrieff
It's partly because they all interact. So actually, isolating the effect of one is difficult. It's also because sticking chemicals into human brains is a very difficult thing to do. So, you know, there's some research done on animals, but not very much Research on human beings that directly manipulates brain chemicals for obvious reasons.
- [27:00]
Co-Host/Interviewer
Because this is fascinating, when people talk about mental health, they conflate it with mental illness. So we talk about depression and schizophrenia as if they're under the same umbrella. When, as anybody knows, and I have people in my family who've suffered from schizophrenia, it is a very, very different condition to depression.
- [27:23]
Joanna Moncrieff
I think it's a very different condition. But there's not. There's not very good evidence for any biological basis for schizophrenia either, really. So it's still a mental illness in the sense that it's an illness or condition that we diagnose or identify on the basis of how people behave.
- [27:47]
Interviewer
I guess what Francis is getting at, I think, is more that depression is something that we probably all experience at one point of our lives to a lesser or greater degree. Schizophrenia is a whole different way, which
- [28:01]
Joanna Moncrieff
I completely agree with. Yeah, yeah, no, absolutely. I mean, I think depression is something understandable and familiar, and schizophrenia is quite, quite a radically different state from our ordinary, everyday lives.
- [28:15]
Interviewer
And I guess the other part of it, and this is, you know, it's difficult to talk about because you never want to talk about people who have a particular problem from a kind of responsibility point of view, because it sort of sounds like blame a lot of the time. So. But I guess you can probably speak about yourself. As I said earlier, like, I know how to give myself or put myself in the state of being depressed. I also have discovered how to get myself out of that state. Right. And I think, I would imagine, you know, obviously Big Pharma people always want to make money from helping people fix their problems. But let's be honest, a lot of people, all of us, want an easy fix for things. And if someone comes along and gives you a tablet, instead of saying, okay, you've got this from, okay, here's what you do. You exercise four times a week. You don't eat any sugar. You don't eat any other crap. You make sure you speak to your family every day. You do this. You.
- [29:06]
Co-Host/Interviewer
I'll give you depression, whatever.
- [29:09]
Interviewer
I mean, that probably will. You know what I mean? There's a whole, like, you have to change your whole lifestyle or we can just give you this tablet. And a lot of people would rather just take the tablet.
- [29:19]
Joanna Moncrieff
Yeah, yeah, yeah. The problem is that we know that if you subscribe to this idea that you have a brain chemical imbalance, you actually do worse. You have worse outcomes, and you think that you can't do anything about your condition, and you are more likely to Believe that you will never recover.
- [29:38]
Interviewer
Yeah, it feels like cancer basically, right? It feels like you've got cancer.
- [29:42]
Joanna Moncrieff
So I think what happens when someone is prescribed an antidepressant? Often they will initially get some sort of psychological benefit, some placebo, positive placebo effect because they think, oh great, at last someone's helping me, I've got an explanation. You know, the drug's going to work. So often people will start to feel a bit better. But because actually the drugs are not a long term solution, probably not really having much impact on your mood other than, you know, other than slightly numbing you, which is probably not helpful in the long run. They don't work. And when people start to realise actually I don't really feel better, then they can feel being in an even worse state because then they think not only do I have this, you know, horrible medical condition that, you know, I need to take a drug to sort out, but I'm not even responsive to this drug. I'm treatment resistant, you know, I'm gonna, it, the treatment hasn't worked, I've got to go back and get the next line of treatment and then that might not work. So actually people can end up in a, you know, really sort of negative and pessimistic state. So although it, you know, it feels like it might be a nice easy a solution and beneficial in the long run, I think it's not.
- [30:59]
Interviewer
And Joanna, we have had on the show on all sorts of different subjects and culture and politics and comedy and music and whatever. Lots of people who have challenged the consensus in their field doesn't usually go that well. People don't tend to take on new ideas that easily. How have you found the response to bringing these ideas forward?
- [31:22]
Joanna Moncrieff
Yeah, that's a good question. Well, there's been a lot of pushback from the psychiatric profession and some from members of the public and some from the media. I think members of the public sort of went two ways. When we published that paper, which is part of what I write about in the book, Some people said oh my goodness, thank you for enlightening me. Now I realize I shouldn't be taking this medication that I was given and has never done me any good anyway way. And then other people, you know, people who'd really changed their whole feelings about themselves, changed their self beliefs, come to see themselves as someone who had this brain condition and you know, was going to need this long term treatment and, and, and found having that idea of themselves challenged, you know, challenged difficult, found that, that difficult to be challenged about that idea, you Know, some of them pushed back and said, you know, it's irresponsible to publish this. You're going to make people feel awful. So, you know, we had those sort of responses. 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. I think they wanted people to go along under that impression, which is why no one has challenged this idea of the chemical imbalance theory earlier. Because actually, it's been known for a long time that the evidence didn't add up. I mean, although I got all the evidence together in a systematic way in this paper in 2022, a lot of people said when I published it, oh, we knew all that. Of course we knew there wasn't evidence for a chemical imbalance. Of course we knew there wasn't evidence for the serotonin theory of depression. And I think the reason that no one had highlighted that before is because actually it suited the profession for the public to go on believing that we had discovered the biological origins of depression so that they would go on subscribing to this medical view and taking the antidepressants. And in fact, they, you know, the psychiatrists who sort of challenged the paper in that way often suggested that, well, okay, you haven't found a serotonin imbalance, but maybe it could be inflammation. You know, there's lots of other theories. It could be inflammation, it could be problems with neuroplasticity, it could be other neurotransmitters. The problem is that none of those, those are all theories about possible biological causes of depression, but none of them have been proven either. And there's much less research in those areas than there is on serotonin and depression. So, you know, yes, there was lots of pushback, but, and as I started with, you know, there are still lots of public information sites that tell people that depression is caused by a chemical imbalance in the brain, but I think there are fewer. Now, I know that, for example, the Australian and New Zealand Royal College of Psychiatrists took down their, their blurb that told people that depression was due to a chemical imbalance. And I think other, some other sites have been changed as well.
- [34:46]
Interviewer
So if we don't know exactly what causes people to feel persistently sad, let's call it that, how much do we know about ways of consistently overcoming that state or getting out of that state?
- [35:02]
Joanna Moncrieff
So we know that the vast majority of people will recover at some point spontaneously. So I Think that's a really important point to say state, because we've sort of created the idea. And in fact the president of the Royal College of Psychiatrists was on the radio the other day saying people don't get better from mental illness on their own. Well, people do get better from depression on their own. Whether you call it a mental illness or not is another matter, but it certainly is classified as mental illness. And so it's important to know that people can get better on their own. And then how people get better depends on the reasons why they have become depressed, the particular individual causes in their situation. So, you know, some people might need relationship counseling to sort out relationship difficulties, some people might need support at work. Some people will benefit from having general psychological therapy, talking therapy, in order to work out why they're feeling depressed. Because we don't all obviously know, and even if we know, we may not be, may not have any clear idea about how we can change those things that have made us depressed. So I think therapy can help with that and I think therapy can also help with processing childhood trauma. Trauma, you know, major, major events. It can help people to build up self esteem, which is often part of the problem as well. So I think therapy can be helpful, but I don't think it's necessarily a panacea or something that everyone, you know, has to have. And then there are general things that improve people's mood or well being on a day to day basis, like exercise, like eating well, like social interaction, like having meaning and purpose. I think that's really important and I think that that is one of the major things that we struggle with in modern life. You know, now that we don't have meaning and purpose given to us in the form of a religion, obviously some people still subscribe, but many people don't subscribe to a religious faith and therefore we have to create our own. And that's not always, not always easy.
- [37:19]
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- [38:36]
Co-Host/Interviewer
Do you think also the part of the problem is, Joanna, that mental illness and mental health have now become an identity? You see it with people in their bios, on Twitter, on social media, say, ADHD, bipolar, etc. If that's your identity, you're not going to want to get better, are you?
- [38:54]
Joanna Moncrieff
Yeah, I think this is a big problem and I think that's absolutely right, that it can, you know, it can give people the impression that they'll never get better. And also it limits people. That's what worries me about this like this, you know, having a mental health identity is that you might think, well, because I've got this thing, you know, this mental health problem, I can't do that sort of job, I can't do that activity. I'm never going to be able to have a relationship. Maybe, you know, so, so. And again, it's sort of this. I mean, I think people who adopt a mental health identity have different ideas about what it really means. And some people, I think, are just saying, I'm a bit different from other people. You know, this is who I am. Some people, I think, you know, have bought into the idea that they have some, you know, problem with their brain. And if you're one of those who's just saying, I'm a bit different, well, you know, maybe that's okay. But again, I sort of feel that it still might be limiting to feel that, you know, you have this difference that's a sort of intrinsic part of you. But people who've really bought into the full idea, they've got a problem with their brain. Well, first of all, you know, there, there isn't evidence that that's true. So they're buying into a, you know, a mistaken, mistaken idea. And that's, that's very limiting. If you, you know, if you're thinking of yourself as Someone who is flawed, who has an abnormal brain, you know, a broken brain as some people refer to it, then obviously you will, you know, you will limit yourself and you will, you know, possibly, possibly not lead as fulfilling life as you could otherwise have led.
- [40:45]
Co-Host/Interviewer
And also as well. And this is, by the way, there's no judgment on my behalf because this, this is not an identity. But there are times where I have embraced this particular type of viewpoint, which is that of being a victim. Life gets, you know, things happen to me and therefore, you know, I'm a victim of life. Etc. How much of this is people essentially assuming the mantle of being the victim and as a result of that they don't have to take full responsibility. In the same way that, you know, people go, you know, well, I have adhd, which means I have outbursts at times, which means I can go around and tell you what I think of you, which is unfortunately how some people behave.
- [41:27]
Joanna Moncrieff
So let me tell you about a little project I did with a student a few years ago. We looked at people's, the blogs of people who identified themselves as being depressed and having significant problems with depression. And we analyzed how people seem to understand their depression, but also what they did about it. And what was very interesting is that most of the people in these blogs were fully signed up to this medical idea that they had something wrong with their brain. And they were signed up because, you know, because this, this made them feel better about themselves. This excused them from feelings of shame, from feelings that they'd let people, other people down or weren't pulling their weight in their family or workplace or whatever. But what was very interesting is that when you moved, when you saw how they wrote about how they'd overcome depression, they all said that they had to take active steps themselves to, in order to change their lives in order to overcome this problem. So none of them were saying that we just took the drug and it fixed our chemical imbalance and everything was fine. They were all saying we had to examine our lives, we had to examine, we had to understand why we felt as we did and we had to do something about it. We realized we had to change something. And that process of change had, had often involved a process of personal growth and development. And many of them felt that they'd become fuller and better people as a result of that self examination process that they'd gone through. So I think that shows that it is important for people to have agency to, you know, examine what this means. What they're feeling is a response to what's gone Wrong for them and what can they do to change it? But it also shows, as you say, how people, you know, do feel ashamed and embarrassed about letting people down. And yes, that it's nice to have a sort of peg to, you know, to hang those feelings on so that you don't have to, you know, keep battering yourself about them.
- [43:41]
Sponsor Voice
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- [43:42]
Co-Host/Interviewer
Because, look, human beings are human beings. And if you're going to give someone an excuse, they're gonna invariably take that excuse.
- [43:50]
Sponsor Voice
They just will.
- [43:51]
Co-Host/Interviewer
Because that's how we are, I think, sometimes. And if we give people the idea that they can overcome something and that they have agency, I really do think that's a more effective solution than to tell people that they're going to be these victims of this awful condition.
- [44:08]
Joanna Moncrieff
Yeah, I do, and I agree with you. And that's why I think it's so important that people know that we don't have, you know, that this idea that depression is a chemical imbalance is not established, is not proven. Because people who have this idea that, you know, they have this brain problem do, you know, and there's research showing this, do feel that there's not much they can therefore do about it. And so they, you know, they sit back and they're relying on the pill that you give them to make them feel better. And you know, that not gonna work because the pills aren't very effective anyway. And so that's one of the reasons why I think it's really important to disabuse people of this idea.
- [44:54]
Co-Host/Interviewer
And because we have to tackle this, because there's gonna be a pretty large swathe of people who are watching this or interview or listening to it going, how much of this is the drug companies involvement, vested interest, profits, etc.
- [45:12]
Joanna Moncrieff
Well, it certainly all got kicked off by that, I would say. So, as I said, the idea that depression was caused by a chemical imbalance wasn't initially dreamt up by them. The people who sort of came up with these theories were psychiatrists and researchers back in the 60s. But it was the drug companies that really grabbed it and ran with it in the 1990s when they were trying to promote the SSRIs and the subsequent antidepressants that have come onto the market. And they, you know, they flooded the medical airwaves with this idea. And then when, you know, the Internet really got going and people got access to the Internet, they flooded the Internet with this idea that depression is caused by a chemical imbalance. I would say that they are very much responsible for having established this idea. In the popular psyche, the drug companies are not that interested in antidepressants anymore. There are one or two coming online, but most of them are now off patent. So they're not really heavily being heavily promoted. Most of the antidepressants that we use now, it's not necessarily down to drug company activity that this idea is being maintained, but I think they had established it so well, and they'd had help. They'd had help from medical institutions that, you know, ran public information campaigns, often with backing from the pharmaceutical industry to, you know, to disseminate this idea, to do disease awareness campaigns, you know, to tell people, basically, if you're feeling a bit down, go and see your gp, this could be a medical problem. So they got lots of help from the medical profession and the medical professional and some medical. Some medical sites, anyway, are still putting this idea forward, but definitely it was the pharmaceutical industry that really popularized it on a wide scale.
- [47:01]
Interviewer
Well, coming back to your conversation you were having about, you know, people feeling like they're victims, the people I feel really, really sorry for, I think most of all is the parents of children who've been told this. And I imagine that's a very difficult situation, because if your child believes this medical theory and they have all the weight of expertise behind it, and you are there kind of going, well, why don't you go for a walk and see your friends more and do this and do that, you are in a very difficult position where you're like the dinosaur who doesn't get it, you know, while your child is basically being drugged for problems in a way that's not actually being solved.
- [47:40]
Joanna Moncrieff
Yeah, I come across a few accounts from parents where that's happened, where their teenage or young, young adult child has. Has gone off and got a diagnosis, and they feel that actually this is, you know, an understandable situation and there could be other ways of dealing with it and, you know, worry understandably about that person, you know, getting started on an antidepressant, but potentially entering into a cascade of medical treatments, you know, which people do, because the drugs aren't effective. So. Yeah, no, I agree.
- [48:16]
Interviewer
There was one other thing I wanted to ask you in relation to the side effects of SSRIs. I don't know if this is true, but I do remember reading in the wake of a number of very highly publicized mass shootings in the US that there was at least a correlation between SSRI use and mass acts of violence of that kind. Do we know anything about that scientifically?
- [48:41]
Joanna Moncrieff
So there is quite a bit of Research that shows a correlation, as you say, between acts of violence and also suicidal behavior and taking antidepressants. Maybe the correlation between suicidal behavior isn't so surprising. It's difficult to disentangle cause and effect. So, of course, you know, people, people who are suicidal get put on antidepressants and people who have violent tendencies may well also be diagnosed with depression and put on antidepressants because they're, you know, that their behaviour is already problematic. But there is a little bit of research that suggests that antidepressants can occasionally make people suicidal and violent and aggressive, particularly young people. I don't know why it's particularly in young people, but that does seem to be a consistent finding. And these studies that show this are randomised controlled trials. So they are studies that are comparing the effects of people taking antidepressants and placebo. So they're not, you know, they're not, they're not. That's factored out the problem of trying to disentangle cause and effect. And some of those studies do suggest that there is a small increase in violent behavior and in suicidal behavior in people on antidepressants compared to people taking a placebo and trying to.
- [50:12]
Co-Host/Interviewer
Something that piqued my interest when we were talking earlier was when you were explaining about all the drug companies, they're no longer interested in antidepressants. The. The patent has expired, therefore there's not much money to be made. And there's a little light in my brain went, so what are they interested in now? And what are they seeking to make money from? And then I thought about the explosions in rates of ADHD diagnosis, autism diagnosis. My conspiracy theorist. Or is there something else going on?
- [50:44]
Joanna Moncrieff
So you're absolutely right. ADHD is a big development area at the moment. There are lots of. Not lots, but there are a few drugs being launched or that were launched a few years ago for adhd, including ADHD in adults, which has obviously mushroomed in recent years. And there are some new drugs for depression being promoted, for example, esketamine, which is a relative of ketamine. And then the. This is my point.
- [51:15]
Interviewer
If you give people drugs, they're gonna feel good for a while.
- [51:18]
Joanna Moncrieff
Absolutely, absolutely. So it's really going in that direction. There is. It looks like the pharmaceutical industry are producing more and more psychoactive drugs that are directly related to drugs that are used on the recreational drug scene. I wonder whether this is really conspiratorial, but I wonder whether they've looked at the opioid crisis in the States and Thought, well, they got away with it, you know, they got a lot of people, they sold a lot of opiates by telling people that they're not, not addictive and they got away with it and maybe we should, you know, try some drugs a bit like that. So there are, there are opiate like drugs being developed for the treatment of depression, believe it or not.
- [52:03]
Co-Host/Interviewer
What?
- [52:04]
Joanna Moncrieff
Yeah, absolutely. There's essence, you want to have a good time.
- [52:08]
Interviewer
There you go. But this is what I'm saying is like if, if you can't legalize drugs or make a profit from giving people, from selling people weed, well you just call it, you know, something else. You add a little thing in front of her or at the end or whatever and you just give it to them and then they have a great time and everybody's happy.
- [52:28]
Joanna Moncrieff
So. So yeah, I mean it's not that ludicrous. That is what is happening. I mean, just to clarify, these opioid drugs are claimed not to have opioid like effects, but it does look as if they do have some sort of opioid type problems.
- [52:43]
Interviewer
Well, they are opioids. You think they have an opiate like effect.
- [52:45]
Joanna Moncrieff
And then of course we've got this huge.
- [52:48]
Co-Host/Interviewer
So can I just pause it there just one second? As somebody whose people seen the effects in my family of depression and addiction, the last thing that you want to do with somebody who is depressed is give them a highly addictive substance.
- [53:01]
Joanna Moncrieff
Yeah, yeah, absolutely, absolutely. Although antidepressants are dependence forming but not, you know, don't cause sort of misuse in the way that opioids do. But yeah, no, absolutely, absolutely.
- [53:14]
Interviewer
Sorry this interview is descended. But I just find this so ridiculous. Like the way we talk about this stuff, it's almost like you're not allowed to like put two and two together anymore and go, well, if you're just giving people drugs that people take recreationally, I know they're probably not going to solve anything.
- [53:29]
Joanna Moncrieff
So esketamine is a good example. If I can just talk about this. So esketamine, which is very closely related to ketamine, essentially has the same effects as ketamine. No one disputes that. And it's been trialed in trials, giving it twice a week to people in trials just as if it was an antidepressant. With the idea that people, people should just be on this for a few months or possibly a few years. I'm sure with the anticipation that people will actually go on it for years and years. And they do depression measurement scales and then they do side Effect scales, one of the side effects being dissociation, and conclude that because your depression symptoms come down after you've taken this esketamine, that you've somehow recovered from your depression. I mean, it's completely absurd. And, you know, and the normal psychoactive effects of ketamine are all contained in the little side effect scale. And it's as if these are completely separate. They're the way that they affect your mood and the way that they, you know, cause the dissociation and you feel.
- [54:37]
Interviewer
So basically, a guy comes into your office and says, I'm depressed. You got to go out and have 10 pints. And then while he's having the 10 pints, you go, how are you feeling? It's so much better, doc.
- [54:44]
Joanna Moncrieff
Yeah, exactly.
- [54:45]
Interviewer
And that's basically what you do.
- [54:46]
Joanna Moncrieff
Yeah, yeah, yeah, exactly. And I mean, not only that, but ketamine and esketamine are both being promoted as rapid onset treatments for suicidal thoughts. So, you know, you come in and you have your infusion of ketamine and someone measures your, you know, suicidal thoughts ratings and they've gone down. And therefore this is, you know, thought to be a treatment. I mean, it sounds like a joke. It does, doesn't it? It does. But actually, this is happening.
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Co-Host/Interviewer
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- [56:21]
Co-Host/Interviewer
It's deeply irresponsible because if any of you followed the story about Matthew Perry, the Friends actor, he was obviously highly depressed, struggled with addiction for all of his life, used ketamine as a way to overcome his addiction, and effectively died of a ketamine overdose.
- [56:36]
Joanna Moncrieff
Yeah, yeah, yeah. Absolutely. And it's not just restricted to him. There was an article in, I think it was the Guardian a couple of years ago that was interesting, which was about how a lot of ketamine clinics were closing down because, you know, they'd been, you know, the market was saturated and too many had opened up essentially and people, and there were people desperate that their local clinic had closed down and they couldn't go and get their next, you know, treatment. So, you know, basically people had become dependent, probably a mixture of psychological and physical dependence on having their regular ketamine infusions. And then suddenly the whole service shut down and they couldn't get it.
- [57:23]
Co-Host/Interviewer
But isn't it interesting, like just the language. And I think it's very important to state, you know, big pharma, that's done a lot of good, let's be honest about that. But the names, Esketamine, you go, a ketamine infusion. What are you talking about? You're just getting off your nut on ketamine.
- [57:43]
Joanna Moncrieff
And the latest thing that's come in is psychedelics. So, you know, psilocybin, psilocybin, ecstasy. And again, you know, there are serious trials of these things going on with this idea that they might cure treatment resistant depression. It's quite interesting. It started out as what's called psychedelic assisted psychotherapy. So the initial idea, which isn't maybe quite so crazy, is that you had a psychedelic experience, you had a trip under supervision and then you processed what you experienced during that trip in some subsequent psychotherapy. And the idea was that maybe the psychedelic experience would give you some insight into why you were depressed or what you might do to improve yourself and your life and your mood. And that that was what was helpful. So, I mean, I still think that's a sort of rose tinted view of what drugs can achieve in people who are, you know, deeply depressed. But there's some logic to it. At least it was acknowledging these are psychoactive substances. You have a psychoactive experience, you have an old, you know, you go into an altered state for a bit. But what's happened is that that has sort of morphed into this idea that actually what they're doing is, you know, fixing some brain chemical receptor problem or some chemical imbalance. And that of course easily translates into the idea that what you need to do is take them long term, just as people take antidepressants long term. And of course that's how it's going to go because it's not a good business model, is it, to have you know, to set up a clinic where you come in and you have one psychedelic experience, a couple of psychotherapy sessions, and then you're cured. Which is. Which is what the initial idea was,
- [59:34]
Interviewer
by the way, on the psychedelic point. It's something that we have talked to one or two people on the show who have suggested that it might actually be effective for things like PTSD and other things. Is there any evidence on that that you're aware of?
- [59:50]
Joanna Moncrieff
So there was a trial done on PTSD and ecstasy, I think. And
- [59:59]
Interviewer
ecstasy is not psychedelic, is it?
- [60:00]
Joanna Moncrieff
Well, it's a little bit psychedelic. It's a bit psychedelic and a bit amphetamine. Like, the. The results showed some benefit. But the problem with all these trials is, of course, you can't blind people at all. I mean, you can't blind people in an ordinary antidepressant trial very reliably, but you certainly can't blind people. If you're giving people ecstasy or psilocybin or something like that, or ketamine.
- [60:25]
Interviewer
Just for people who are not medical experts, you're not poking their eyes out. What you mean when you say you can't blind them is they know they're taking ecstasy?
- [60:32]
Joanna Moncrieff
Yes, yes. So you set up this trial where you compare taking ecstasy to taking a placebo tablet and you give people the placebo with the idea that people won't know whether they're getting the real drug or the placebo. But of course, if you're comparing something like ecstasy with a chalk or sugar tablet, people will know the difference. And it's the same with antidepressants to some extent, although it's probably less immediately obvious. So the problem is that you can't effectively blind. You can't effectively disguise what people are getting. And so there's probably an enhanced placebo effect associated with thinking that you're getting the real active substance. So they. So this trial of ecstasy and ptsd, I think they did find a small effect, but there are concerns that it, you know, that it was basically due to. Due to this unblinding effect, due to the fact that people knew what they were getting.
- [61:34]
Interviewer
What about psilocybin, more specifically? Is there any evidence on that?
- [61:38]
Joanna Moncrieff
So there are a couple of small trials of psilocybin trying to revive my memory of them. There's one that's compared them to an. Compared psilocybin to an antidepressant and didn't find any difference. That was done by a group in this country. There might be another one that's compared it with placebo. I Think and found some immediate difference, but much less difference when you follow people up a bit later, as you would expect if this was if they were actually picking up. If what you're picking up is people's drug induced experience, there's going to be
- [62:18]
Co-Host/Interviewer
people listening and watching this who are already thinking themselves, you know what, I've been on antidepressants for a while, maybe it's time to get off. What advice would you give? Because I'm sure it wouldn't be just take your antidepressants, throw them in the bin and go cold turkey.
- [62:32]
Joanna Moncrieff
It's a really important question. Thank you for asking me. So the most important thing to say is don't do that, don't just put them in the bin, particularly if you've been taking them for long periods of time, because they can be associated with quite severe withdrawal symptoms. So people need to come down on them slowly. Now, some people will need to do that very slowly, particularly if they've been on them for years and years in order to minimise the withdrawal symptoms that they will get. Withdrawal. The other thing that's important to say is that withdrawal symptoms include emotional symptoms like anxiety, tearfulness and, you know, changeability of mood, feeling down, feeling sad. They include a lot of emotional symptoms in the same way that, you know, coming off alcohol or heroin, you know, any psychoactive substance, you know, messes up your mood when you're coming off it. So people will experience emotional symptoms when they're coming off their antidepressants. They shouldn't just assume that that means they're having a relapse because I think very commonly that has happened, that people have started to come off, started to feel a bit anxious, a bit more emotional than usual, assume that they're having a relapse and that they need to go back on their medication. And many of those people then think, oh, well, I've just got to take it for life. Which is really tragic because actually probably if they just reduced, if they'd known what was happening, A and B, reduced more slowly, they might well have got off their antidepressants. So people should, you know, people need to be aware that there are withdrawal symptoms. These include emotional symptoms. Also some people get physical symptoms like dizziness, like feelings of electricity going through the brain, quite typically. And these can be minimised by coming off slowly and particularly coming off. It's particularly important to come off the last bit slowly. So to get down to low doses, then don't just throw it in the bin, keep reducing the dose very slowly. There are guides now to help people with that. The Royal College of Psychiatrists have some good information on their Stopping antidepressants section of their website. That was written by a colleague of mine who's had personal experience of coming off antidepressants. And he's also co authored a book called the Mauds DD Prescribing Guidelines, which gives people lots of information. It's massive and very dense and quite expensive, but it's something that people could potentially recommend their GPs to get if their GPs were uncertain about how to help people or if people were worried that their GPs were telling them to come off too fast, as I think is probably quite often the case.
- [65:17]
Co-Host/Interviewer
So, I mean, that's worrying that the GPS don't really know how to get people to come off these drugs, because if they come off too fast, what you're basically saying is that the side effects can be quite severe.
- [65:30]
Joanna Moncrieff
Yeah, absolutely. And there's evidence that some people, probably, particularly people who come off too fast, will get into a persistent withdrawal state or a persistent, you know, a persistent state whereby they often feel foggy, debilitated, tired. Some people can't, you know, can't get out of bed, people have to stop work or reduce their hours, can cause all sorts of social problems. And I know more and more about this because along with colleagues, I've set up a little deprescribing service in the mental health trust that I work in. And we are increasingly referred people who are in these terrible states having come off antidepressants too fast. So it's really. And sorry. And I brought that up because I think that not that many GPs and doctors are aware of this problem, are aware that. That there are these persistent states that people can get into if they come off too fast. It's tragic that we're not aware enough about that because actually, the same problem was shown with benzodiazepines back in the 1980s. It was shown that people who. Some people who came off benzodiazepines, again, showed persistent problems, often persistent neurological symptoms and persistent anxiety. So it does seem that some drugs, you know, if you come off them too fast, can really cause a lot of damage.
- [67:03]
Co-Host/Interviewer
And you're saying persistent. What does that mean medically?
- [67:07]
Joanna Moncrieff
So, good question. It means that the symptoms can go on for months and sometimes for years. So people have reported these sometimes for years. And while we're on that subject, can I just bring up the subject of persistent sexual dysfunction? I think that's also something.
- [67:23]
Co-Host/Interviewer
Thank you for looking at me when you said that. Joann
- [67:28]
Joanna Moncrieff
I just think it's something that's really important and again, something that's not nearly well recognized enough by the profession as well as by the public. So it's well acknowledged that antidepressants cause sexual dysfunction while you're taking them because they're disrupting the serotonin system. That's not in dispute and affects a lot of people who take them. What has become evident over the last couple of decades, I would say with increasing reports, is that some people will have persistent problems with their sexual functioning after they stop taking their antidepressants. And not only has this come out from reports of patients, it's evident from animal studies that show that young animals, rats and mice that are treated as adolescents or young adults with antidepressants show persistent problems with their sexual functioning after they've stopped. The, after this drug has been stopped. We don't know how common this problem is. I mean, I hope to goodness that it's rare. But there are increasing reports and there have been a couple of attempts to try and work out how prevalent it is, one of which suggests it might affect up to around about 10% of people who stop taking antidepressants. And again, we don't know how long the problems might last. It might just be a few months for some people, but there is definitely people who report that it lasts for years. And many people say that it's not just sexual functioning, it's their emotional functioning as well, that they feel generally numbed emotionally and sexually. So really important for people to be aware of that and to be aware that their doctors may well not be aware of that.
- [69:19]
Co-Host/Interviewer
Joanna, it's been an absolute pleasure. Thank you for coming on the show. Final question is always the same. What's the one thing we're not talking about and we really should be?
- [69:28]
Joanna Moncrieff
Oh, gosh. I mean, I think we've covered everything that I need to cover. As I've said, my mission is to make sure that people are informed. Maybe I can just sort of finish by saying that I don't have any beef with people taking antidepressants or seeking a diagnosis of depression as long as people understand what the implications are and particularly what the effects of antidepressants are and how little we, we know about what the long term consequences might be.
- [70:00]
Interviewer
Well, thanks for coming on and sharing that with people. Really valuable. We're going to go to Substack where people are going to ask you their questions now. So head on over to triggerpod.co.uk and we'll see you there. Should Tina just be taking all these medications for adhd? I worry about taking something during these developing years. Shouldn't they get help but talk about the issues and given problem solving strategies instead? It.