E109 - Is Depression a Medical Illness? (w/ Prof. Joanna Moncrieff)

Joanna Moncrieff is a British psychiatrist, researcher, and professor of critical and social psychiatry at University College London (UCL). She is widely recognised for her critical perspectives on psychiatric medication and the biomedical model of mental health. Her work challenges conventional ideas about the role of drugs like antidepressants and antipsychotics, advocating instead for a nuanced understanding of their effects. She has authored several books, including The Myth of the Chemical Cure , A Straight Talking Introduction to Psychiatric Drugs, and Chemically Imbalanced: the Making and Unmaking of the Serotinin Myth and has published numerous academic papers, such as her notable 2022 paper on the serotonin hypothesis of depression.

Interviewed by Dr. Alex Curmi. Dr. Alex is a consultant psychiatrist and a UKCP registered psychotherapist in-training.

Prof. Moncrieff's new book Chemically Imbalanced can be found here:
https://www.amazon.co.uk/Chemically-Imbalanced-Making-Unmaking-Serotonin/dp/180399679X

Studies discussed during the podcast:
https://www.nature.com/articles/s41380-022-01661-0 - the serotonin paper
https://www.nature.com/articles/s41380-024-02462-3 - critiquing "biological depression"
https://pubmed.ncbi.nlm.nih.gov/37778356/ - the RADAR study of anti-psychotics
https://pubmed.ncbi.nlm.nih.gov/23824214/ - the Dutch study of anti-psychotic reduction

If you would like to invite Alex to speak at your organisation please email thinkingmindpodcast@gmail.com with "Speaking Enquiry" in the subject line.

If you would like to enquire about an online psychotherapy appointment with Dr. Alex, you can email - alexcurmitherapy@gmail.com.

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Disclaimer: None of the information discussed in this podcast is intended as individual medical advice, changes to medication plans should always be made via discussion with the prescriber. Abrupt withdrawal of medicaion can cause serious adverse effects. 

Transcript

What I was most shocked about is that there seemed to be some psychiatrists who just don't want the general public to know, um, that there isn't research to support the serotonin theory of depression. I think that we need to have honest conversations with people about the limitations of our knowledge. 

Welcome back. If you've been listening to the podcast for the past few months, you know we've recently been having a lot of conversations. around the limits of psychiatry, the limits of what we understand about the brain, and also the limits of the effectiveness of psychiatric medications. We've had conversations with people like Rose Cartwright about problems with psychiatric diagnoses, Mark Horowitz about de prescribing antidepressants, with Richard Bental about the limitations of our understanding of psychosis, among others. 

Today, we're [00:01:00] continuing that conversation with Professor Joanna Moncrief. Professor Moncrief is a British psychiatrist, researcher, and professor of critical and social psychiatry at University College London. She is widely recognized for her critical perspectives on psychiatric medication and the biomedical model of mental health. 

She's the author of several books, including The Myth of the Chemical Cure, A Straight Talking Introduction to Psychiatric Drugs, and Chemically Imbalanced, The Making and Unmaking of the Serotonin Myth. Today, we discuss several topics such as the validity of depression as a biomedical illness. and consequently the value of antidepressants as treatment for depression. 

We discuss her high impact 2022 paper questioning the serotonin hypothesis of depression, the potential value of antipsychotic drugs for conditions like schizophrenia and bipolar disorder, how some of these critical perspectives on psychiatry could influence the redesign of [00:02:00] public mental health systems. 

the current state of play of open discussion and debate within the psychiatric community, and much more. Similarly to my conversation with Mark Horowitz, there may be some difference, ultimately, in my view and Joanna's view about the value of antidepressants and some other medications, particularly when it comes to more severe mental health conditions. 

And for me, it will certainly be an ongoing process of looking more at the research and having more conversations like this on the podcast from people of all different points of view. But I did find this conversation very compelling and I hope you will too. I think it's worth pointing out just as a disclaimer that absolutely none of the information discussed in this podcast should be taken as direct medical advice. 

If you are currently taking some form of psychiatric medication and wish to consider stopping, you should absolutely speak to your prescriber before taking any action. This is the Thinking Mind [00:03:00] Podcast, a podcast all about psychiatry, psychology, psychotherapy and self development. As always, thank you for listening. 

If you'd like to support the podcast, check out the links in the description. And now here's today's conversation with Professor Joanna Moncrief. Professor Moncrief thank you so much for joining me today. Thank you for having me Alex. The first thing I'd love to discuss with you is something I'm sure you've discussed in public quite a lot, your 2022 meta analysis about the serotonin theory of depression. 

Huge paper, so impactful, been discussed on many big podcasts, many big newspapers. The first question I'd like to ask, I'd really like listeners to understand what this paper is about and what, what can we infer from this paper. So my first question would be, what is serotonin? What is the question that this paper set out to answer? 

So, one of the ideas about what causes depression is the idea that it is caused by an abnormality or imbalance of certain brain chemicals. This is an [00:04:00] idea that was first thought up back in the 1960s by psychiatrists and researchers who were working on early antidepressants, uh, early drugs that became known as antidepressants. 

And, um, then it, uh, and then it was picked up by the pharmaceutical industry and really publicized in the 1990s and onwards, uh, as part of promotional campaigns. Surrounding the, uh, a new range of antidepressants called the SSRIs. So the most popular version of this idea was the idea that depression is a result of abnormally low sero levels of the brain chemical called serotonin and. 

That idea was used in these promotional campaigns to persuade people to take antidepressants. It was used to persuade people that depression is not, um, just an ordinary reaction to life circumstances, but is actually a brain [00:05:00] condition that can be addressed. using sophisticated and targeted drugs that rectify the underlying brain mechanism. 

So that's why it's been an important idea. It was the rationale for the promotion of the SSRI antidepressants and, and for all antidepressants, in fact. Um, and so that's why I thought it was impossible. Uh, it was important to look at the research behind this. idea or theory, um, or hypothesis as it's sometimes known. 

Uh, and so, uh, a few years ago, I got together a team and we looked at all the different areas of modern research into links between serotonin and depression and found that there was no good or consistent evidence in any of those areas of research that supported the idea that [00:06:00] depression was caused by low serotonin levels. 

And we would say specifically lower serotonin levels being released in the synapses, the space between nerve cells, is that what we're specifically saying? So, so serotonin is what we refer to as a neurotransmitter. That means it's one of the chemicals in the brain that helps to transmit neurological impulses between nerves, between nerve cells. 

Um, and so the idea was that, There was, uh, there was a deficiency of serotonin, so not enough impulses were being, that serotonin would have transmitted, were being, uh, transmitted, and the, um, action of SSRIs is that they they inhibit the protein that transfer that that remove serotonin from the gap between the nerve cells where it actively works to [00:07:00] transmit the impulse. 

So by removing it from this area, SSRIs are thought to, sorry, by, by inhibiting the transporter protein that removes the serotonin, SSRIs were thought to increase the activity of serotonin in the synapse. So what do you think is the, the correct conclusion to draw from your paper that this particular, that this particular hypothesis is false? 

So, it's very difficult to prove, and if not impossible to prove a negative. The conclusion from our paper is that the hypothesis is not true, that there's not good strong evidence to conclude that it is the case that depression is caused by low serotonin. And that's, that's important because, because People had, [00:08:00] that's what people had come to believe. 

That's what people had been led to believe by all the promotional campaigns that have been going on over the last few decades, they had been led to believe. Not that this was just a hypothesis that, you know, there might be some evidence for, but there might be some evidence against, but that it was something that had been established, um, that was known. 

And it was a major narrative that was used to justify the prescription of and of specifically SSRI antidepressants for a long time. Yes, absolutely. Yeah. Are you worried about any conclusions, particularly that the mainstream media have drawn from this paper that aren't accurate? And I can give some examples. 

So some conclusions that I've heard often on podcasts, so podcasts can be guilty of this sort of thing. uh, conclusions that, based on this paper, antidepressants by and large don't work, that SSRIs don't have any clinical value, uh, that [00:09:00] depression doesn't really have any strong biological underpinnings. 

Do you worry, or have you seen any examples of this particular paper having these conclusions drawn from it? So the question about whether antidepressants work or not is a complex one. Um, and, uh, I think this paper contributes to the view that they do not work in the way that has normally been presented. 

Um, and, uh, That actually calls into question whether they work at all, I would say. Um, and, and I've, as well as writing a serotonin paper, doing the research behind that, I've spent decades writing about antidepressants, the way that we understand them and looking at the evidence behind them. And my conclusions have been that there is very minimal evidence that they are actually any better than a placebo. 

If you look at placebo controlled trials, the difference [00:10:00] between the antidepressant and the placebo is very small. It's two points on a 50 point scale. That's almost certainly possibly possible to be accounted for by, um, the fact that these, the people in, in these trials can often guess whether they're taking the antidepressant or the placebo. 

So people On the antidepressant, we'll get a bit of an amplified placebo effect. So I don't think there's actually really strong evidence that they are better than placebo, but even if they are, let's assume that that two point difference is some sort of pharmacological effect, not a, not an amplified placebo effect. 

There are other ways of understanding what they might be doing. in, um, how they might be affecting people with depression than the traditional idea that they are correcting a chemical imbalance or targeting some sort of possibly unknown biological dysfunction. So antidepressants [00:11:00] are what we might call mind altering drugs. 

Um, And by that I mean a drug that enters the brain, changes the way that the brain normally works, changes our normal brain chemistry, and therefore creates changes in our normal mental states of one sort or another. We normally think of mind altering drugs in relation to recreational substances, But there are many other drugs that don't necessarily produce very nice effects. 

So they're not, they're not used recreationally, but nevertheless change the brain and change our mental states in one way or another. Now, if you give someone a mind, someone who is depressed, a drug that changes normal mental states, it's likely that it will affect. their feelings, that it will affect their depression temporarily. 

If you give someone who's depressed a dose of heroin or indeed of alcohol, um, [00:12:00] they may temporarily feel less depressed. That's what we would expect. Now, antidepressants don't have, um, the sort of, uh, appealing or very strong mind altering effects that alcohol or heroin do, but they do subtly alter mental states. 

And one of the alterations they produce, which is very consistently reported by people who take them, is they produce a state of emotional numbness. And, and, uh, and they numb both negative but also positive feelings and people also talk about, you know, finding it difficult to cry or express their emotions when they're taking antidepressants. 

And obviously if they cause those changes, those will impact on someone who is feeling depressed. Now, being emotionally numbed by a drug may or may not be useful. Um, it, as I say, if we If we discount the amplified placebo effect, maybe this [00:13:00] accounts for some of the two point difference that we see between antidepressants and placebo. 

But it's a very different proposition from taking something that is working by targeting or rectifying an underlying abnormal mechanism. Generally, people are cautious and cautious about Taking a drug that numbs their feelings. Um, and people would be worried that taking this particularly taking it long term might be, you know, potentially harmful or even damaging in some ways. 

Uh, and so that's why I think it's really important that we, that we acknowledge that this is what antidepressants might well be doing. And when you say the other thing that you are concerned that people are, you know, maybe concluding wrongly on podcasts, you suggested that one of these things might be that there's no, um, biological or neurophysiological basis to [00:14:00] depression. 

But I would argue that we don't have any evidence that there is. And I don't think it's correct to assume that there is, you know, that there, there's lots of evidence that assumes that, yeah, that, that, sorry, lots of evidence that suggests, you know, this mechanism may, may be involved, this mechanism may, may be involved, um, as, as well as all the evidence on serotonin. 

So people have, you know, put forward theories to do with inflammation, theories to do with Neurogenesis and, and, um, uh, the processes that, uh, you know, are involved in the repair of, of neurological tissue, uh, and, and lots and lots of other, um, brain processes have been proposed to be relevant in depression, but none of them are supported by convincing evidence either. 

So, you know, the state of play at the moment is we, we don't have good evidence to conclude that depression is a result [00:15:00] of a biological process or mechanism. Um, and, and therefore, I think we have to regard antidepressants as not as mechanism targeting drugs, but as drugs that change the normal state of our nervous system. 

And that should, that should ring alarm bells for us. You know, if you take something that changes our normal biology day in, day out, uh, for long periods of time, and often people are taking antidepressants for years on end, there may be harmful consequences. And I would argue that we haven't. put enough effort and money into researching what the consequences of long term antidepressant use are, and that there is some evidence that, um, that, that long term use, well, there's good evidence that long term use can sometimes be associated with some, uh, you know, really catastrophic situations such [00:16:00] as these, um, people who, uh, come off antidepressants often, you know, often too quickly and end up with these prolonged withdrawal states, which Dr. 

Horowitz, um, I'm sure described to you, and also evidence that some people get persistent sexual dysfunction after coming off antidepressants. Yeah. Thank you. So Going briefly back to the serotonin paper, so, you would say that's part of a much larger body of evidence. which is overall skeptical of a biological basis for depression and therefore skeptical of antidepressants as a useful intervention. 

So it kind of, for you, it seems forms a small but important piece of the puzzle. Is that a fair way to put it? Yes. Um, I suppose the serotonin theory of depression has been one of the best studied theories of the biological basis of depression and therefore showing [00:17:00] that this well studied theory Uh, is not supported by evidence. 

Highlights that, you know, that, that, that decades of research have not actually produced any, any evidence to support, to support this way of viewing depression and all the other, you know, supposed theories. Have not been around for so long and have not been tested so well or research so intensively many of them for many of these you know new proposed theories such as You know the relationship between depression and neurogenesis. 

It's not really they're not really even theories It's not really even clear what you how you would test them or what exactly is meant to be involved in in the causation of depression They're often, you know, very vague, uh, ideas that people are putting out there. [00:18:00] I'm going to just mention a couple of papers, uh, talking a little bit about potential relationship between serotonin system and depression, and you can tell me what you think. 

So in researching this for this interview, I found that in 2015, there was a meta analysis published by Cambates et al in the Journal of Affective Disorders. And that suggested that depressed patients showed reduced serotonin transporter availability in certain regions, particularly the limbic system. 

In October 2022, so I guess just after your serotonin meta analysis, Eritzo et al published a paper in Biological Psychiatry examining what they called serotonin release capacity. And I believe this was in the frontal cortex. So the capacity for serotonin release specifically after a dose of amphetamine. 

and it showed depressed individuals seem to have a smaller serotonin release capacity, than non depressed [00:19:00] individuals. So, so what do you make of, of papers such as these? So the Kanbiz and Howe's paper we included in our serotonin umbrella review. Um, so they, they detected some evidence of reduced serotonin transporter activity in some areas of the brain but not others and in some studies but not others. 

One of the um, intriguing things about this is that actually if you had lower, lower levels of the serotonin supporter you would expect, transporter, you would expect higher levels of serotonin in the synapse and higher serotonin activity. So if this is a correct finding, And I would suggest that, um, that it's probably not, that it's probably just Uh, publication by the publication bias that you see with, um, early on in, in researching a topic with, you know, small positive studies being published and negative ones not being published. 

But if it is a real finding, it would suggest that depression is [00:20:00] linked with higher serotonin, not lower serotonin. I also, um, most of the patients in, in those studies were taking antidepressants and I also suspect that it's a consequence of antidepressant use. Rather than, uh, actually, uh, uh, link with depression. 

So, so that's, um, and, and, and that was a problem with most of the research that we looked at. That the numbers of people who weren't taking antidepressants involved in any of these studies was very small. And, of course, antidepressants are, uh, Um, are modifying the serotonin system in some way. I'm not trying to suggest they don't act on serotonin in some way. 

They're changing, you know, the normal state of the serotonin system. So if you're investigating people with depression who are on antidepressants and comparing them to people without, without depression who are not taking antidepressants, you're going to find a difference. You haven't necessarily proved anything about depression. 

Um, and in fact there was a very, [00:21:00] one of the studies that we looked at was a large, a large meta analysis of, um, women who'd been involved in, um, uh, in studies of hormones, um, after the menopause, and some had been involved in some HRT studies. And they measured all sorts of things, including serotonin in those studies. 

And they found that There was, seemed to be a, they were looking at plasma levels of serotonin. There was a slight, a weak relationship between serotonin and, um, and having depression, but then they analyzed it according to whether people were taking antidepressants or not. And it turned out that the relationship was actually between taking antidepressants. 

and um, uh, abnormally low serotonin, um, serotonin levels. Um, and that people who were depressed and not taking antidepressants didn't show, didn't show that effect. So that was a problem with a lot of [00:22:00] research. Now the The study that came out in 2022, after our public, after our paper was published, was a very small study. 

It involved, I think, 17 people in total. Around about five of them also had Parkinson's disease, which is relevant because Parkinson's disease, although it mainly involves, um, uh, areas of the brain that are Um, that are involved with the dopamine system. It, it's, it's also known to affect lots of other brain chemicals, including serotonin. 

So that's one problem with that paper. The second one is, is that it's, it's very small. The third one is they claimed it was a, it was a direct study of serotonin, which it was not. It was, um, a study of. A technique for measuring the, um, what is thought to be the release of serotonin in response [00:23:00] to, uh, giving, giving people amphetamines, um, the validation for. 

Whether that process actually does measure serotonin or not was, was based on a small study that was done in pigs. Um, so it wasn't a very direct study anyway, and the, but the most important thing probably is that the findings were only, only statistically significant. If you use a one sided test, well, you know, everyone uses, everyone uses and should use two sided tests. 

Um, and secondly, they were anyway, um, influenced by outliers. So there were some extreme values and if you remove them, um, you didn't see any difference between the groups. So it was a very small study and it was not a robust finding in, um, by any measure. Another thing just to say, I think on the serotonin research, if this is all right, is that, um, We, we looked at [00:24:00] the research on the, uh, gene for the serotonin transporter, and this was interesting in a couple of ways that, that highlights some general points about this research. 

So, first of all, what was interesting about it is that a number of. small, uh, genetic studies conducted from the 1990s onwards suggested there might be a relationship between this gene and depression and getting depression. Um, and then, uh, and then when the studies on the actual gene and depression started to show up as negative, people started to, people proposed that, It might not simply be the effect of the gene. 

It might be an interaction between having the gene and being exposed to, um, trauma or abuse, uh, during childhood that predisposed to depression. So, uh, geneticists started looking for interaction effects. And again, several groups suggested that they had [00:25:00] found good evidence of this interaction effect. Um, then over the last few years, a couple of very large genetic and very good quality genetic studies have been conducted that show there is absolutely no evidence of any link between depression and the serotonin gene, and there's no evidence of any interaction effect either. 

So that's, I think, just an interesting illustration of how You know, in the early days, there are often some suggested find to suggestive finding, um, often because of, you know, probably selective public publication, uh, you know, due to everyone's enthusiasm to get out positive results and, uh, you know, overlook negative ones. 

Um, and that really you need, you know, really big. Conclusive good quality studies to work out whether there is really an effect in an area. So that's one, that was one interesting finding from the genetic research. Another thing that was [00:26:00] very interesting is that the, the studies that looked at the interaction effect all, um, all involved measuring, asking people whether they'd been victims of abuse or trauma in childhood, some, some in adulthood too. 

And. These, the studies found overwhelmingly that there was a very strong relationship between having been a victim of trauma or abuse and subsequently getting depressed. So there was no genetic effect in these studies, but there was a very strong link between depression and, uh, environmental adversity. 

Is there good evidence? So I, I talked to Robert Plowman on the podcast before, and he talks a lot about genetics influencing personality. Is there good evidence that genetics may predispose neuroticism in the big five and that being in higher neuroticism could [00:27:00] predispose you to depression if you had certain stressful life events. 

So I, I don't know whether I'd say this good evidence because I can't say that I've really gone through it with a fine tooth comb, um, recently, but I would say that it makes sense that there's going to be some genetic contribution to personality, of course. Uh, and, and exactly, as you say, that there may be some contribution, um, in terms of, you know, how emotionally sensitive, um, or reactive people are. 

Having said that. Um, my understanding on the, uh, research on temperament, you know, temperament, there was this research that supposedly showed that temperament was, um, very strongly genetic. Uh, it turns out that actually that research is not nearly as convincing as, as you might think. And that actually the. 

genetic component, although probably there is some genetic component, but it's not as strong as, as was originally proposed. Yeah. So when I talked [00:28:00] to Robert Plowman, which was back in 2021, so it was a while ago, but his contention was on average personality traits are around 50 percent heritable. So that does not mean of course, 50 percent genetic exactly, just for the listeners, it means 50 percent of the difference is likely to be explained by genetic differences. 

rather than environmental differences. And he would say that there were some personality traits which were more strongly heritable than others. So that was his position at the time. But perhaps we would need to have him back on to get a bit of an update about that. Yes. And I'd need to update my knowledge on all the, the genetic research. 

I probably think that 50 percent is an overestimate, but, uh, I mean, I know the schizophrenia genetic research quite well, and the 50 percent figure there for the heritability of schizophrenia comes from, um, uh, comes from these twin studies that, uh, but it's actually, it doesn't even come from the [00:29:00] twin studies overall, it comes from one twin study that found the highest heritability rate, and actually there are plenty more that find much lower rates. 

Yes, I actually spoke to Richard Bentall, and we released a podcast with him last week. And he, I think in his view, a heritability of more 25 percent makes sense in light of his reading of the research, but I'd definitely like to discuss psychosis a bit later on lingering on depression. You know, I do feel there is this sense that particularly when, again, when discussed in the media, we can fall into this, into this kind of binary. 

Do antidepressants work or not? Does depression have a biological basis or not? Uh, is there any distinction worth making between more mild to moderate depression and more severe depression? And I raise this because I think you said earlier that depression can be characterized as like a normal reaction to adverse [00:30:00] circumstances and certainly when I see people who are mildly to moderately depressed I can definitely understand that, particularly for example in my psychotherapy work. 

When I've seen severe depression what that often looks like is difficulty getting out of bed. not eating or drinking to the point of physical harm, what we call psychomotor retardation, so slowing of thought, uh, speech, movement, etc. You know, just intuitively seems to have more of a biological, um, stronger biological element there. 

Is it worth making these distinctions? Should we be making these distinctions clinically? Should we be studying these patient groups separately? What do you think about that? Well, a couple of things. The, as far as links between serotonin and depression are concerned, the research has not distinguished between people who have mild depression or severe depression or reactive or melancholic depression or however you want to classify it.[00:31:00] 

So we don't have any evidence that there is a subgroup. of people, uh, whether they've got more severe depression or however you want to classify it, that does have some, um, you know, biological basis or certainly not one that involves serotonin, um, so far because that research just hasn't been done. Um, I, I, I generally try not to, not to characterize depression as a normal reaction to circumstances because I think it can, embrace very different reactions and some of them are very extreme. 

So just as you describe, you know, I've also frequently encountered people who, um, have had what we would call very severe depression, stopped eating or drinking, taken to bed. Um, in my experience, it is still generally a reaction, um, to something that's gone on in, in their lives. So this, this pattern of depression is often seen [00:32:00] in elderly people and often it follows, um, uh, retirement, um, bereavement or, or, or maybe a reaction to isolation and loneliness. 

And, and I think that just because. Something, a reaction is extreme doesn't necessarily imply that it has a medical or biological basis. Um, of course, sometimes, um, you know, sometimes there is a biological factor that, that changes people's behavior. You know, we know there are neural, there are brain diseases like Parkinson's disease and dementia, um, that affect how people behave and also affect people's emotions. 

But I think that, I don't think that we can assume that depression is like that unless we find a particular mechanism, um, that, you know, that confirms that it is like that. I think the, I think the position [00:33:00] that, that we have to, assume is that depression is, you know, is a meaningful reaction until proved otherwise, not, not the other way around. 

So that being the case, I'm curious if you're seeing someone, for example, in an outpatient clinic, someone presents with something looking like depression. I mean, my first question would be. Do you even think depression is a clinically useful concept, like do you use it in your day to day practice? I don't think it's a terribly useful concept, no, because I think everyone with depression is in a different, reacting to a different situation, often in, you know, in, uh, very individual ways. 

I mean, I think the idea of being depressed is, is useful, you know, that's, that, that has, that has a meaning, but this idea that everyone who is depressed has a thing called depression is, you know, which is the same and each one of them is already to me starting to, um, go off on a tangent and to miss the real nature of, of [00:34:00] what it is to be depressed. 

Mm hmm. So it's useful to describe a particular state of consciousness, perhaps. So, so yes, there's such a thing as being depressed, um, which overlaps with being sad, uh, and overlaps with being disappointed and overlaps with grief and all sorts of other, other states. Um, but, uh, but that doesn't mean there is a thing called depression that people have. 

Right. Right. So, you know, I think talking in that way is, is, is confusing. Yeah. It's interesting how language can very subtly and unconsciously frame our understanding of things. Yes, absolutely. Absolutely. I think that's a very, very good point. Uh, you know, and I think it does, I think that's a really important point, actually, you know, I think this is one of the problems with this whole idea that was, you know, put about by the pharmaceutical industry initially, that depression is a chemical imbalance, that, that that's exactly what people have. 

Have, you know, come to believe that depression is, is a disease. It's a brain disease. It's caused by a chemical abnormality. And it's a, [00:35:00] it's a thing that we have. It's a thing in the head that's gone wrong. Um, it's completely separate from who we are and, um, and our life experience because diseases generally are, you know, diseases have their own, their own logic. 

They're not necessarily connected with, with our, our personality and experiences and feelings and things. So, so I think, you know, I think that's, that's been quite a harmful thing that people have taken on board this, to my mind, uh, misleading idea about what it is to be depressed. They've taken on board this idea that they've got this thing in their heads that needs to be corrected by Something that you know acts on their brain in some way Rather than trying to understand the meaning of what they're going through. 

Despite that I do find when Interacting with people who you could say they're depressed, there are a lot of commonalities and perhaps and what [00:36:00] they're experiencing and how they're experiencing the world. So, for example, they might report low moods, disturbed sleep, disturbed appetite, low energy, fatigue. 

But it's also interesting for me to observe the psychological patterns. Someone who's depressed will often have quite negative thoughts about themselves, quite negative thoughts about the future, uh, even negative thoughts about the past and what's happened to them. When seeing patients like that, how do you approach interviewing them, assessing them, coming up with a treatment plan? 

What's your approach with that? Well, to me, the most interesting thing is, is why are you feeling like this? And what can we do about it? Um, and, and, you know, that's, that's my problem with Seeing depression as a disease or a condition, you know, that you then don't necessarily ask those important questions or don't necessarily focus on them enough. 

Um, so [00:37:00] yeah, so, so I think, you know, I think trying to help someone with depression is, is trying to explore the reasons for the depression, what it's a reaction to, and what might be done about that might not be, might not be easy to change it. Um, but, but usually I think it is useful to. Try and identify what the problem is, even, even if it might be difficult to, to address it. 

What are some really common problems do you think people encounter that makes it more likely for them to fall into a depressed state? Well, first of all, as I said, you know, there's lots of evidence that, uh, things, you know, that things that have happened to people in the past influence their v increase, can increase their vulnerability to depression. 

So, you know, being a victim of abuse. Uh, or neglect in childhood can increase people's vulnerability. Then the common things that people are reacting to are relationship difficulties, um, separations, divorce, relationship [00:38:00] breakdowns, um, difficult family, difficult family situations, being unemployed or being in an employment situation that is stressful, over demanding, being lonely. 

Lacking direction and meaning in life, you know, all these, I think all these things contribute to, contribute to making people feel depressed. And then that being the case, and being depressed being so common, do you think we really need to be rethinking not just the use of medications like antidepressants, but also how our mental health services are even designed, because I feel like the way our public mental health system is designed right now is not actually very well equipped to help people deal with relationship problems, to help deal with unemployment, help deal with loneliness or meaninglessness. 

So, in your view, since these and others are like [00:39:00] important contributing problems, should we be really seriously rethinking the wider culture, but also our public mental health systems as well? So, absolutely, and I think, you know, the one most important thing is that we need to de medicalise the area. You know, we need to stop thinking about this as a medical condition and see it as, uh, a reaction to difficult social circumstances, um, in which case the, the most helpful institutions are likely to be, you know, social services, social work. 

Um, family therapists, employment specialists, debt advisors, and financial advisors, because of course, one thing I didn't mention is that a huge, huge contributor to making people depressed is financial, um, insecurity and poverty. So, so yes, I think, you know, I think we need to rethink, rethink how we think about mental health problems, how we frame them. 

[00:40:00] Um, and take them by and large, particularly, um, you know, less severe mental health problems out of the medical arena, uh, so that we can then prioritize the sorts of social interventions that are more likely to be helpful now that this, this is happening to some extent with things like social prescribing. 

So there are some initiatives that are trying to push things that, that, in that direction. Um, but I think we could go further along. further in that direction by really, um, you know, taking mental health as I say, out of medicine. And then what do you see as the role of the psychiatrist? And are we to become obsolete? 

Do we have a role? Do we have a role in perhaps more severe or extreme situations? Should we retrain as therapists or something else? How do you see the role of psychiatry at large? Well, that's a good question and a big question. I'm not sure that psychiatry. [00:41:00] Has or should have much role in helping people, um, with depression or with milder mental health problems. 

Uh, I think it quite probably creates more problems than it, than it solves in that arena. Um, when, when you think of more severe problems such as psychosis or what we often call schizophrenia. Um, manic depression and, and, uh, situations like that, there, there is a need to provide care and sometimes I would argue control or containment of people who are in extreme mental states such as psychosis. 

And I think that's, uh, that's something that, that needs to be done. I think there's a role for medication in that. Um, so, so people who are involved in, in that, um, area of work need to have at least some medical training, whether they need to be full scale medical doctors are not sure, [00:42:00] but, you know, you could also argue does a dermatologist needs to have a training in absolutely everything. 

Maybe, maybe medicine needs to be organized, you know, differently and needs to be more specialized early on when it comes to psychosis. We did, so last week's podcast was all about psychosis. So if you guys want to have a really clear definition of what that is, what that looks like, I'd encourage you to look up that podcast. 

But when it comes to psychosis, would you say there is a, is there a more clear biological underpinning given, for example, that you can induce a psychotic episode with certain drugs like amphetamines or with sleep deprivation or that studies have suggested that drugs like Uh, Cannabis make it significantly more likely that someone has a psychotic episode. 

Do you think there's a clearer biological underpinning? Do you think it's maybe more appropriate to classify psychosis as a so called illness rather than depression? And therefore there's more of a [00:43:00] role for medication? What are your thoughts on that? So, I don't think that we have really any better evidence that schizophrenia or bipolar disorder, um, are, uh, biomedical conditions with, um, biological mechanisms that cause them than we have for depression. 

So, uh, so, you know, the dopamine hypothesis has been around for a long time as an explanation, as one explanation for the etiology of schizophrenia and Uh, in my view, the supporting evidence for the dopamine hypothesis is also weak and inconsistent. You are right to point out that we can, you know, create, uh, psychotic states with, with induced psychotic states with drugs like Cannabis and stimulants, sleep deprivation, sleep deprivation, of course, can change people's moods too. 

So, you know, we, we, if you do physical things to the brain [00:44:00] by giving drugs or sleep deprivation or ECT or whatever, yes, we, we change, uh, change our normal consciousness and thinking and feeling and, um, can produce, can mimic some of the states that we see in, in psychiatry. But I think by and large that schizophrenia and Is, is not like that, is not just a result of, of a brain mechanism, maybe, uh, you know, as we were talking earlier about how personality may have some, there may be some genetic contribution to personality. 

I expect there is some genetic contribution to a tendency towards psychosis. So you know, I expect there's some biological component. of that sort, I don't think that we are going to identify a specific mechanism that causes schizophrenia or manic depression. And, and then what, why do medications help with these [00:45:00] conditions? 

Is it similar to antidepressants where you would say they induce an altered state of consciousness or what would be your explanation for that? Yes, exactly. And I don't think with antipsychotics, this is that controversial a point to make really. You know, antipsychotics are, they used to be called major tranquilizers, you know, that they're all tranquilizing substances. 

And the, the, the doctors, the psychiatrists who first used antipsychotics back in the 1950s, Um, referred to them as, as major tranquilizers or as, um, neuroleptics, uh, or neurological inhibitors. They sometimes, uh, referred to them as, and they were, they were very enthusiastic about them. They thought they were very useful, but they didn't think they worked by targeting an underlying disease. 

They thought they produced an unusual state of sedation that was different from the sort of sedation that you got with the barbiturates, which were the commonly used [00:46:00] sedative drugs of the time, which just knock people out. What antipsychotics did is they seemed to produce a state of tranquility. Um, that was a sort of state in which people were slowed down and their emotions in particular were dampened down without them just being sent off to sleep. 

Um, so I think that's what antipsychotics are doing in psychosis, particularly they are. Um, reducing the emotional, um, salience, the, the, uh, the emotional salience and the, and people's preoccupation with psychotic symptoms and ideas. Um, so that people often, um, often still have some psychotic ideas sort of going on in the background when they're on antipsychotics, but they're not as troubled by them and they're not at the forefront of their mind anymore. 

And of course, you, uh, participated in a study, the so called RADAR [00:47:00] trial, research into antipsychotic discontinuation and reduction, which sought to, I believe, answer the question, is it worth maintaining individuals with a history of psychosis on antipsychotics in the medium and the long term? And that study seemed to suggest, correct me if I'm wrong, that when antipsychotics were slowly reduced and discontinued, there was a higher rate of so called adverse effects, relapses of psychotic episodes, readmissions to hospital under the Mental Health Act. 

But there wasn't any particular benefit in terms of that individual's social functioning. So, did that study meaningfully change your view about the utility of antipsychotics? Because, unlike with antidepressants, it seems like you're making the argument that even though they're not treating an underlying disease, they are in fact useful. 

Was that in part because of studies like this? Well, I've, I've, I've always, um, I've always [00:48:00] suggested that antipsychotics can be useful for some people who are acutely psychotic. The, the point of the Radar study to my mind was to Look at the outcomes of helping people to come off antipsychotics, people who'd been on them, you know, had, uh, were established on them, and to see what the outcomes of that were. 

Um, and, and what was different about the RADAR study compared to previous studies of that sort was that we did a gradual reduction of antipsychotics rather than taking people off and switching people onto a placebo as was done in the previous studies. So, I was disappointed that, um, that, that, Doing a gradual reduction of anti psychotics didn't seem to reduce the risk of having a relapse compared to the studies that had done a, you know, an abrupt, an abrupt cessation of anti, of anti psychotics. 

We never expected that. There wouldn't be some [00:49:00] increase in the rate of relapse. Um, but what we saw was that the risk, the increased risk of relapse was similar to, to others, uh, you know, to, to the other, uh, randomized control trials that had been placebo controlled. Um, so, so yes, that, you know, that was disappointing. 

And as you point out, there weren't any benefits to people, um, over the two years of the initial followup, but, um, I didn't. Personally, really expect there to be benefits at that time, at that time point, we modeled the study on a study done in the Netherlands, which was done with first step people with the first episode of psychosis. 

That was, um, published by Lex Wondering in 2000 and, um, 11, I think, or possibly 13. Um, and, and, uh, they, well, well, in fact, the original paper was published. The, the, the writeup of the original trial was published in 2008. And [00:50:00] in their original trial, they found also that there was an increase in relapse in people who'd had, uh, a gradual reduction of their antipsychotics. 

Compared to people who'd been randomized to maintenance, but then they did a follow up, uh, at seven years. And they found that in the follow up people who'd been randomized to antipsychotic reduction or discontinuation had, um, improved social functioning compared to people who were randomized to antipsychotic maintenance treatment. 

And that relapses had evened out over the follow up. So, I didn't personally really expect there to be benefits at two years, and we are conducting a follow up, maybe we'll see benefits in the follow up, maybe we won't, I don't know, we're, we're, it's a different group, um, the radar trial is people with Um, multiple episodes of psychosis and often they were people who had been on anti psychotics for very long periods of time. 

So probably much more difficult to take them off and, and, [00:51:00] um, and see good outcomes in that situation. But, uh, but yes, I don't, you know, I, I don't think, um, I don't, the fact that people didn't, you know, show improved functioning at two years wasn't a surprise to me. And I suppose that's a huge difference between those two studies because the study you participated in, those are people who've had, as you said, multiple episodes of psychosis. 

The study in the Netherlands, that's just one episode and my understanding is if you've just had one episode, that's kind of quite a meaningful difference in terms of likely future outcomes. And there's an idea that treating psychosis early is likely to result in better outcomes. But then the other point I'm thinking about when I'm hearing you describe both of those studies is. 

Is there any attempt to give any other form of treatment to perhaps ameliorate difficult social circumstances? Maybe I'm thinking about some sort of trauma focused intervention. Richard Bentall told us [00:52:00] trauma is quite highly correlated with instance of psychosis. So I wonder about a study that can look at not just the use or not of anti psychotics, but the introduction of other interventions which may benefit the patients psychologically or socially. 

Has any work like that been done? Any plans for that kind of work? So, so, so, yeah, so, so, first of all, just to address your point about the difference between people with a first episode psychosis and people with recurrent episodes, one of the important differences, I believe, is that people with a first episode of psychosis haven't been on antipsychotics for very long. 

So they, their brains haven't had time to, um, adapt to the presence of a drug, which is what we know leads to withdrawal effects. Now, um, antipsychotics are known to produce some immediate withdrawal effects, such as agitation and sleeplessness, um, possibly even psychotic symptoms. There are [00:53:00] case reports of, of people who don't have a history of psychosis, but have been on antipsychotics or antipsychotic like drugs for other reasons. 

developing psychosis when they're withdrawn, um, but that's an immediate effect. But another effect that they have that I think can occur a bit further down the line is increasing the risk of having a relapse of the underlying disorder. The withdrawal of antipsychotics may increase the risk of having a relapse of the underlying condition. 

So, I spoke about this with Mark Horowitz as well, who said, you know, When people are on antidepressants for a long time and they come off them, they can feel like they're becoming depressed again. But could that be simply the withdrawal syndrome, syndrome of the antidepressant? Um, with lithium in people with manic depression or bipolar disorder, for example, there are several studies that show that your risk of having a relapse when you come off lithium is higher than it was before you started it. 

So there's something [00:54:00] about the process of withdrawal that precipitates or stimulates what is probably, usually I would think, a manic episode because lithium is, again, a very sedating, neurological inhibiting, neurologically inhibiting substance. So, um, So, so the length of time that people have been on medication, I think is probably, uh, uh, you know, going to determine their outcomes when they've, when, when they come off it. 

Although, although, although I have to say when, you know, we've looked at whether that determines people's risk of relapse in the first two years and it didn't. Maybe it will do over the longer period, but so far, right on on the issue of psychosocial treatments. I just wanted to mention a very interesting study that was conducted in, um, Australia in the famous early intervention service in Melbourne, in Melbourne. 

Um, and this was a placebo control trial comparing anti psychotics with high quality psychosocial [00:55:00] treatment for people with acute psychosis. It was only a pilot trial, so it was quite small, um, but I can't remember the exact figures. I think it's 60, 60 so people in it. So it's not tiny. Um, and, and, and they found that at six months, the outcomes were the same for people who were randomized to antipsychotic treatment and people who are randomized to, um, uh, to, to psychosocial treatment. 

They didn't include people who were considered to be, you know, high risk of, um, committing. you know, harm to others or harm to themselves. Um, so it was a slightly limited population, but most trials obviously excrete such people. So not necessarily much more, much more limited than other trials. So I think that's, you know, that's an important finding. 

Um, there was, you know, there were dropouts. In fact, there were more dropouts from the, the, um, drug treatment group than the psychosocial treatment group, but there were dropouts from both groups and crossovers, you know. people [00:56:00] stopping medication in the drug group and starting medication in the, um, in the psychosocial treatment group. 

But nevertheless, I think that that trial, along with, um, other studies, mostly done in, in the past, back in the 70s and 80s, suggests that there are at least, there is at least a proportion of people who can get through a psychotic episode with psychosocial treatment with really good social support, um, and, you know, psychological therapy in some circumstances too, uh, without using medication or with minimal use of medication, you know, maybe occasional use. 

Yeah, and I guess that's not super surprising, speaking from my clinical experience. Where it seems like a hell of a lot of psychosis not all of it But a lot of it seems to be around feeling unsafe Feeling under attack feeling a lack of powers if you look at someone's delusional thoughts very often [00:57:00] I would say the vast majority of the time they have a paranoid quality a defensive paranoia I'm under attack. 

Someone's trying to harm me. I have no control so It doesn't surprise me. And of course we know, again, clinically, it's a spectrum. Someone can go all the way from a relatively normal baseline to a full blown psychotic episode. And there's every stage in between, and often people kind of fall into psychosis quite insidiously sometimes over years. 

So that being the case, it doesn't surprise to me, surprise me that giving someone a feeling of control, a feeling of safety, of support, of autonomy can go some ways towards, you know, treating a condition like this, even if it was in parallel with a medication. It doesn't necessarily have to be a substitute. 

Yes. And, and, and psychosis as well as depression is strongly related to experiences of, um, you know, adverse events in childhood, such as [00:58:00] experiences of abuse. Um, we're almost out of time, but I would like to talk a little bit about almost the state of debate and conversation within the psychiatric community. 

Uh, a lot of things you talk about often gets a lot of pushback from the so called mainstream psychiatric community. Uh, particularly the serotonin paper we've talked about. What, what kind of pushback and criticism do you often get? Do you, do you ever, do you ever in your view get sort of bad faith criticism? 

Criticism that's coming from a place not of seeking to understand the truth, but perhaps alternative, uh, motivations? Well, I, I think there are psychiatrists who are very uncomfortable about It's being exposed to the public that we do not know the biological basis of depression. And so, you know, there were a lot of people [00:59:00] who, uh, went to great lengths to try and discredit, um, the serotonin research. 

Um, first of all, you know, first of all, the reaction was, oh, it's not important. We all knew that anyway. And then they were saying, oh no, no, but there is some research. Uh, you know, in serotonin, and if it's not serotonin, there's this theory and there's that theory. So, you know, desperately, it seemed to me anyway, trying to persuade the public that no, no, don't worry. 

You know, there is, there is some biological basis for depression. We may not know what that is, but we can assume that it's there. Um, and so, you know, someone's saying, no, we can't assume that it's there. Actually, you know, the, the, the most well researched and well defined theory is not supported and everything else is even, you know, weaker, um. 

was perceived as being very threatening. Um, and I think that, you know, I think that goes back to some of the issues that you've [01:00:00] mentioned about what, what is it to be a psychiatrist? And for some people, you know, being able to offer a, uh, medical solution, a pharmacological solution to some, to a common. 

conditions such as depression is a very important part of being a psychiatrist. I mean, speaking very much from my, my own personal point of view, I feel quite comfortable discussing these topics because a lot of my work is in psychotherapy. So very much being in the trenches with someone week to week and helping sort of sort out their problems really at quite a granular, granular level. 

And if there was convincing scientific research. that medication was really important, then I'm on board with that, and the opposite is also true for me, and everything in between. So I, I personally feel that that lack of investment offers me a sort of flexibility in how I can think about things. And I suppose what you're saying is a lot of people you [01:01:00] receive criticism from are very heavily invested. 

in different ways in medical understandings of mental health, uh, medical theories and also like pharmacological models of treatment. Yeah. And I think what you say about discussing things with, with people is, is the key, really. I think, I mean, what I was most shocked about is that there seemed to be some psychiatrists who just don't want the general public to know, um, that there isn't research to support the serotonin theory of depression. 

And I think that we need to have honest conversations with people about the limitations of our knowledge. And that does, um, raise questions about what antidepressants are doing. Uh, I'm not, I have never said that people shouldn't take antidepressants and I wouldn't stop people from taking them, but I think that people need to be informed. 

That we don't [01:02:00] understand what they are doing. We do not, we cannot justify their use by the idea that they're rectifying a chemical imbalance or a serotonin abnormality. Um, you know, therefore we're really not sure what they're doing. Um, the evidence that they work is also rather limited and flimsy. Um, and I, I, you know, plenty of people who I have conversations with along these lines still decide that they want to take antidepressants and that's fine as long as, you know, they've been informed, they've had a chance to, um, to know the limits of our evidence and also of course that they've been informed properly about harmful effects of antidepressants. 

Joanna, thank you so much. Where can people find out more about your work? So I've got a website, which is joannamoncreef. com. Um, I've just published a book called Chemically Imbalanced, which is published by Flint Books and available from, um, all, uh, booksellers in the UK. And [01:03:00] I'm on Twitter and blue sky. 

Perfect. Joanna, thanks so much. That was very interesting. Thank you.