Dr Rupy: Today we're going to have an uncomfortable conversation, but very necessary one about antidepressants and the theory that these drugs work for depression by correcting imbalanced chemicals in our brains. Hi, I'm Dr Rupy, I'm a medical doctor and nutritionist. And when I suffered a heart condition years ago, I was able to reverse it with diet and lifestyle. This opened up my eyes to the world of food as medicine to improve our health. On this podcast, I discuss ways in which you can use nutrition and lifestyle to improve your own well-being every day. I speak with expert guests and we lean into the science, but whilst making it as practical and as easiest possible so you can take steps to change your life today. Welcome to The Doctor's Kitchen Podcast. Our guest to discuss this topic today is Joanna Moncrieff. She is a professor of psychiatry at University College London and works as a consultant psychiatrist in the NHS. And she is author of numerous scientific papers, including a major review that showed there was little evidence to support the idea that depression is caused by a serotonin abnormality. Her most recent book, Chemically Imbalanced, The Making and Unmaking of the Serotonin Myth, is what we're going to be discussing today. Now, this was a complete eye-opener for me. For years, I believed in the pharmaceutical washed message that antidepressants worked because of a genuine brain chemical imbalance that we corrected with medications. This is not proven. Today, we'll discuss overuse and misrepresentation of psychiatric drugs in the public sphere, the changing philosophy of mental health, and how we got to a point where over 8 million people in the UK alone use antidepressants. We discuss what serotonin is, how we measure it in the body, why the imbalance theory is inconclusive, whether antidepressants have good evidence that they work, and their many side effects. Now, I just want to make this clear that this episode is not meant to shame or belittle anyone's experience with medications for mental health. But my aim is to provide you with accurate information about how we can safely treat these problems and offer informed consent, weighing up appropriately the pros and cons of medications like antidepressants. The use of these medications has well-recognised withdrawal and dependency effects and should not be stopped without strict supervision of your medical practitioner. I can't emphasise this enough. Do not stop these medications or any other medications without speaking to your medical practitioner first. And we've also linked to the Maudsley de-prescribing guidelines in the show notes for practitioners educating themselves on this if they're listening to today's podcast and how you can do this with your patients as well. Like you'll hear right at the end of today's podcast, Joanna still uses antidepressants in circumstances, weighing up the pros and cons, and that is key. It is about weighing up the pros and cons and the potential downsides of these drugs that have been underplayed for decades. And that is what today's podcast is all about. I really hope you enjoy our conversation, you find it educational, you find it sincere, and you find it measured. And if you want more about the story of how we got here, I highly recommend Chemically Imbalanced, the book that Joanna wrote. It is written so accurately and so passionately, but it really does depict just how we need to reassess our relationship with the pharmaceutical industry, particularly within the profession of psychiatry, but I'm sure this is mirrored in lots of other specialities as well, as we briefly discuss at the end of today's podcast too. On to my podcast with the wonderful Professor Joanna Moncrieff. Professor Moncrieff, thank you so much for being here. I thought we would start by just giving a bit more of an introduction into you and your career in psychiatry for our listeners. I think that would be really useful and then we can dive into what will probably be an uncomfortable conversation to hear for a lot of our listeners and viewers. Should we start there?
Joanna Moncrieff: Yep, that's fine, that's fine. So I did science A levels and then went and did medicine at medical school. I was always quite interested in philosophical issues and politics and so I suppose I was drawn to psychiatry because that that that highlights those sorts of concerns. So I went into psychiatry after I finished my medical degree and my foundation year and went into psychiatric training, did the psychiatric exams and and became a consultant psychiatrist and and did academic work and research. So I got an academic post. And I suppose my interest in drugs started, drug treatment started quite early on because it is the predominant form of treatment that people are given in this country, whatever your diagnosis. Almost everyone who comes into psychiatric services is prescribed some sort of drug or another, often more than one. And I became interested in how the way that these drugs were depicted in the textbooks was not always consistent with what I with what I saw. So for example, the drugs that are prescribed for people with psychosis and schizophrenia were described in the textbooks as being revolutionary new treatments that helped people recover from schizophrenia and move out of hospital and live normal lives. And what I was seeing was a lot of people who were tranquilised and in those days they were prescribed quite high doses, probably higher than today, and you know, they were shuffling around looking sedated. And that and and so I got interested in what are the drugs actually doing and might it not be quite as we are told in the textbooks.
Dr Rupy: What what year was that roughly when you were?
Joanna Moncrieff: So that's in the 1990s. I'm starting to train in psychiatry and it was in the very last years of the old asylums. So there were large numbers of patients with long-term chronic problems on the wards in those old hospitals before they were finally shut down.
Dr Rupy: Yeah, so the stereotypical picture of these asylums that we see mainly in movies these days of institutions where people were housed. When were they actually shut down eventually in the in the UK?
Joanna Moncrieff: So starting from the late 80s, running through to the early 90s, they were finally shut down. And they were shut down piecemeal, you know, ward by ward, and people were moved out, often into residential homes or nursing homes, sometimes, you know, into independent flats or back to their families.
Dr Rupy: Yeah, got you. And and just give us a a sense of the thinking around medications at this time because from my understanding of what I read about in your in your book, Chemically Imbalanced, it's there was more of an appreciation of depression being caused by specific life events and something that could be managed with the, you know, the help of a psychiatrist or another therapist. It wasn't so much seen as a a a diagnosis that needed a a chemical intervention or a pharmaceutical intervention. Am I am I right in thinking that?
Joanna Moncrieff: So there were surveys done around that time that showed that the general public felt that depression was caused by divorce, unemployment, having been abused or maltreated as a child, and that treating it with a drug was not not going to get at the cause, was maybe going to numb people a bit, but probably wasn't it wasn't a helpful long-term solution and might also make people dependent. And people were probably influenced in their thinking at that time by the fact that the benzodiazepines had been so widely prescribed and had caused severe dependence in in many people. So so that was the view of the general public. There there had always been a view within the psychiatric profession that depression was a medical condition and had some sort of biological mechanism underpinning it. But it wasn't a view at that time that was very widely known or or accepted.
Dr Rupy: Okay. And so this this biological model of depression was relatively new at around this time that you were having thoughts about whether we should be.
Joanna Moncrieff: So so it wasn't it wasn't new. That that biological the idea that depression is caused by a chemical imbalance, by an abnormality of one of our brain chemicals, has been around since the 1960s. The first paper that put that across suggested that it might be an abnormality of the brain chemical called noradrenaline. But around the same time people were also suggesting that serotonin might be involved. So that idea had been already articulated back in the 1960s and it had in fact been investigated in research programs in the 1970s. Those research programs hadn't found any evidence for any abnormalities of those brain chemicals. So so although that idea was still around, it wasn't it wasn't very influential, I would say at that time.
Dr Rupy: So talk us, let's stay in that sort of history phase for a moment. Just talk us through how we got here given the the lack of evidence that you've just stated there around this chemical imbalance theory. Like how do we get from that to today without the advent of much more evidence to to state the contrary?
Joanna Moncrieff: So that's the, you know, that's the really crucial question and the answer is very simple, the pharmaceutical industry's massive marketing campaign that started in the early late 1980s and early 1990s to promote their new range of drugs, the SSRIs, the selective serotonin reuptake inhibitors, which they were marketing for depression. And now the what's important is the background to this is that the best-selling drugs in the 70s and 80s had been the benzodiazepines. The best-selling drugs for mental health problems, and they were they were massive drugs, they were real blockbusters, very widely used.
Dr Rupy: What kind of names were they?
Joanna Moncrieff: So they are drugs like Valium, Librium, Lorazepam, Clonazepam. So they're they're still used but prescribing rates has have declined because in the 1980s it was recognised that they could cause dependence, that people could experience really really debilitating withdrawal symptoms when they stopped taking them, that they were really difficult to get off. And so so benzodiazepines got a bad reputation and government started to encourage doctors to stop prescribing them, to limit their prescribing. And the and this reputation also extended to I think the whole idea of prescribing something to numb people, prescribing people to prescribing something to people who were unhappy with their lives to zonk them out a bit and just make them forget. And so when the pharmaceutical industry came up with a new range of drugs which they were hoping would would replace the benzodiazepines, they wanted to position them as something more than a tranquiliser or something that just numbed you. They wanted to position them, they wanted to persuade people that they were drugs that would actually target the underlying problem.
Dr Rupy: Yeah. And just sticking on benzodiazepines for a moment there, now we recognise the withdrawal effects, the addictive effects of some of these commonly used and still used medications. Prior to that though, am I right in thinking that these were sold as advocates for for people who are going through tough times. It was it was widely promoted as safe, non-addictive, again, maybe using some of the marketing spin that we've seen since.
Joanna Moncrieff: Absolutely. So the benzodiazepines were brought in in the early 1960s and they were marketed as a safe replacement for barbiturates and people were told that they would not cause addiction and dependence problems like the barbiturates had done. And they were also told that the benzodiazepines were much safer. So the benzodiazepines are safer than barbiturates which were very toxic drugs, but they also cause dependence and addiction problems. And that became that became apparent certainly by the 1970s actually and and then by the 1980s there was widespread press coverage, prime time media programs about the problems of benzodiazepine dependence, lots of people reporting how how difficult they'd found it to come off the medication even if they'd only been taking what they were prescribed by their doctor. These weren't people who were, you know, trying to abuse them, buy drugs on street corners or you know, take someone else's prescription. They were just taking the drugs as prescribed and still experiencing withdrawal problems.
Dr Rupy: Gosh. And the thing that stuck out to me just about that timeline is that that's 20 years. That's 20 years of people using these medications without a concerted flagging of of the fact that these did have addictive properties. I mean it would have been fairly obvious to a modern day doctor now to recognise some of those withdrawal symptoms in patients, but it still took that amount of time for the government to to change tact on on the advice.
Joanna Moncrieff: Yeah, yeah. So actually there were warnings about the dependence problems more or less from the beginning, certainly from the mid 60s there were people flagging that there are dependence problems and the pharmaceutical industry try hard to blame the patients to say, oh no, it's just in certain patients who have an underlying, you know, propensity for for addiction and substance misuse. So so they they they managed quite successfully to sort of keep the whole dependence problem under wraps for for a couple of decades. But by the by the late 1970s more and more prominent people are managing to get into the media. But even then it takes, you know, it takes another 10 years for the problems to really be properly recognised.
Dr Rupy: Yeah, yeah. And I I guess that's in a time where we didn't have social media, we didn't have, you know, rapid access to communications, people's stories, you know, it's very easy to suppress. But I guess now we have like a whole other set of issues when it comes to PR. So we have the backdrop of a playbook that's been used like this before with a a drug in this element. And you you mentioned, you know, moving the industry and the profession wanted to move away from drugs that just zonk people out and then income these these other drugs. Before we start talking about the use of those and and the studies around them, I think let's bring people up to speed with serotonin itself, you know, the molecule, where we find it and what the basis of this this chemical imbalance theory actually was.
Joanna Moncrieff: Yeah, so serotonin is a chemical that is present in various parts of the body including the brain. Actually most of your serotonin is in your gut and then quite a lot is in your in in the platelet cells that are in your blood, those are the cells that are responsible for clotting. And only a small proportion is in your brain, but there is some serotonin in your brain and it is one of the chemicals that helps to transmit the electric impulses from one nerve cell to another. So it's referred to as a neurotransmitter and there are lots of other neurotransmitter chemicals that we know of now. So that's what we know about serotonin. What we don't understand very well is what serotonin related neurotransmission in the brain actually relates to or controls. There is serotonin all over the brain. It's produced in in one part of the brain but then distributed to to different parts. And people have looked at the role of the possible role of serotonin in our in appetite for food, in sexual desire and and activity, in sleep, and of course in mood and cognition and things like that. And the only area, having looked at all these areas of research in quite a lot of detail recently, the only area I would say where we're really reasonably confident that serotonin has some specific effect is in the area of sexual activity. Drugs that interfere, drugs that act on the serotonin system affect sexual functioning and it seems to be that if you increase serotonin activity, you depress sexual functioning, you you reduce people's libido and you know, cause all sorts of sexual problems.
Dr Rupy: That sounds almost counterintuitive to what we've been told about serotonin generally that the fact that you're increasing it subdues your sexual function.
Joanna Moncrieff: So serotonin has this reputation now, doesn't it? As being the happy chemical. And and I think because it sounds like, I mean it's not the the word is not derived from serenity but it sounds a bit like serenity. So I think people associate it with that. So you know, being calm and happy, being in a good place. The the evidence that it is has anything to do with happiness is the evidence for its role in mood and depression. And you know, I I did this big project to show that actually the evidence that serotonin has anything to do with depression is is is very weak. And then there's then then there's some evidence from animal studies that it might be that it might have a role in various forms of behaviour or you know, thinking processes. But that evidence is very inconsistent. You know, one study finds one thing and another study basically finds a contradictory finding and it's difficult to really come up with any interpretation of all that evidence.
Dr Rupy: And I guess for the for the listener, that's a that's a really key point here because if you've got different laboratories doing similar investigations on serotonin and they find opposing results, then that's a sign that, you know, there's something that we really do not understand going on here and there is nothing to hang your hat on.
Joanna Moncrieff: Yeah, absolutely.
Dr Rupy: You don't have the confidence that you can replicate these studies in in different laboratories.
Joanna Moncrieff: Yeah. I mean what it means is you know, we we don't really have evidence that serotonin has any particular or has a particular role, I should say in in behaviour or cognition. It's not to say it it doesn't have some role, but we haven't pinpointed that at the moment.
Dr Rupy: Okay. And and how do we measure serotonin levels at the moment?
Joanna Moncrieff: Gosh, that's a good question. Because I I think one of the bug bears that I have or I had when I was dishing out any medication is you want to have a biomarker of success. And as we'll go into, the the PHQ nine questionnaire is deeply flawed. I had no idea it was funded as well by the pharma industry. That was brand new news to me when I read that in your book. But I like to see like a marker of success. So you know, if we're using a statin, the cholesterol comes down, apolipoprotein B comes down. When you're using an antihypertensive, you want to see your blood pressure improve. With depression, you're relying on a score that's deeply flawed and conflicted. And there isn't a biomarker of success, particularly as we've been selling this as a chemical imbalance. We should have some biomarker but.
Joanna Moncrieff: So so this is this is really important to state. We we can't measure serotonin in the brain directly in in living human beings. We can measure it at postmortem and people have measured it at postmortem. But when we're looking at living human beings, it is measured indirectly by looking at serotonin receptors which we can visualise using brain scanning techniques, or in various other ways. We we can we can measure it in the blood and plasma. We can measure one of the metabolites of serotonin in the cerebrospinal fluid that also circulates around the brain. So there are indirect measures but but not currently any direct.
Dr Rupy: Okay. And so going back to this chemical imbalance theory that was suggested in the 1960s, why was it so pervasive up until, you know, the 1990s and beyond and even to today? You know, what what what was it about the chemical imbalance theory that stuck and what studies did people hang their hat on when they were talking about this such that it became, you know, the foundation for for the medications?
Joanna Moncrieff: Well, I think the important thing to say is that there were no studies really that people were hanging their hat on or putting forward to support this. This was a marketing enterprise, a marketing activity. So you know, the pharmaceutical industry just deluged the airwaves and the media as far as they could manage to to get into it with this idea in the in the 1990s that depression was caused by a chemical imbalance, particularly a lack of serotonin in the brain and that their new drugs, the SSRIs would help correct that imbalance. And they just said that again and again and again to doctors and when they had the opportunity, they said it to the general public. In this country, the pharmaceutical industry are not allowed to advertise directly to the general public except that of course now with the internet they have they have sites and they support other organisations that do. So so really we more or less effectively do have direct to consumer advertising, I would say now. But but we still don't have television advertisements or you know, big sort of billboards. In the US, direct to consumer advertising was legalised in 1997 and from that time onwards people have been seeing advertisements about antidepressants which have been telling them that depression is caused by a chemical imbalance and showing them, there's a famous advertisement for Sertraline, an SSRI called Sertraline, which is consists of this blob that looks very unhappy to begin with and there's a sort of grey sky above it. And then we're given a little picture of of nerve cells with serotonin molecules looking very sparse, not very many of them. Then the blob starts taking Sertraline and you get more serotonin molecules and then you see the blob looking happy. So you know, that's what people have been presented with for for a couple of decades. And there haven't there haven't really been major studies that that people have cited to support this. There have been studies done and some of them found links between serotonin and depression and some of them didn't find links.
Dr Rupy: Okay. So it's random.
Joanna Moncrieff: Yeah, as as we showed when we when we did this review in 2022 and we got all the modern research on on depression and serotonin together, if you collect it all together, some find positive results, some find negative results, some some find, you know, no effect at all. And all together, there's no real signal that serotonin is related to depression.
Dr Rupy: Okay. So just to anchor the listener, if I've got a group of patients that everyone agrees is suffering with depression and I have, quote unquote, you know, normal or euthymic people on the other side that don't have a history of depression or active depression, has there ever been a study that demonstrates some of the, you know, byproducts of serotonin that we can measure in the cerebrospinal fluid or the blood or maybe using MRIs that there is a difference in the serotonin levels, i.e. the serotonin levels in the depressed group is lower than the group in the normal or euthymic.
Joanna Moncrieff: So so there have been studies that have done exactly what you said, compared people with depression with people who don't have depression, don't have a history of depression, and they've compared them in terms of their they've measured their serotonin levels in the blood, they've looked at their serotonin levels in the cerebrospinal fluid, they've looked at the serotonin receptors, they've looked at a protein called the serotonin transporter protein which transports serotonin, which effectively deactivates serotonin, takes it out of the synapse. And they've looked at the gene for the serotonin transporter protein. And some of those studies have found some association between serotonin and and depression, but of found that the, you know, there are indications of higher receptor numbers in people with depression, for example, than than the control population, but some have found higher levels in the controls and some have found no difference. And if you put all those studies together in in each of the different areas, this is what we did in our review, then you find that overall it doesn't look like there is any evidence of of an effect of of of there being a different level or activity of serotonin in people with depression compared to people without depression.
Dr Rupy: Okay. So what we can conclude from that is that there is no basis for the chemical imbalance theory.
Joanna Moncrieff: Yeah. Okay. Yeah.
Dr Rupy: And and just for, you know, our non-science listeners, so you did this systematic review, it came out in 2022. Can you just talk through what a systematic review is and what it entailed for you and and who you collaborated with?
Joanna Moncrieff: Yeah, can I just go back and ask answer the first question though? So yeah, sorry because I so there's no evidence that that serotonin is involved in depression. I suppose the way to put it is that the evidence that serotonin is involved in depression is weak and not conclusive. Okay. Yeah. And and I think that's an important way to put it because one of the one of the reasons I did the study was I realised that I realised that people that the general public believed that the link between serotonin and depression was was proven, was established. And most psychiatrists and researchers actually knew that the evidence wasn't very strong, but no one had put all the evidence together. And by putting the evidence together and showing how weak it was, we were able to say, look, this idea is not established. There's a bit of evidence, but there's also a bit of contradictory evidence. Overall, it's very weak and we can't say that it's proven. It really just remains as a as a possibility.
Dr Rupy: Okay. So it's possible for a well-meaning psychiatrist to look at a bunch of studies that showed positive results that actually underpin the serotonin imbalance theory, the chemical imbalance theory. But when you actually put them all together in a systematic way, which you'll talk through in a second, you find it's inconclusive because of the mixture of both pro and evidence that's pro and con.
Joanna Moncrieff: Absolutely, absolutely. Yes, yes, that's that's exactly right. And and I think that's important because because I think what these surveys showed that were done in the early 1990s that that showed that people, you know, understood depression as as being a reaction to divorce or, you know, adverse life events. They they showed that that we have an intuitive understanding of depression as as something that is a reaction to things that happen in our lives, an understandable reaction. And therefore to change our thinking and to persuade ourselves that it's not that, it's it's it's a disease of the brain, it's a biological mechanism that is independent of our of our personalities and our life circumstances, there needs to be some justification for for changing your view, for accepting that biological view. And I think I think that biological view became established because people believed that the link between serotonin and depression was an established fact. And had they been told this is a theory, it's a possibility, I don't think people would necessarily have have you know, have been so willing to reject their previous sort of intuitive understanding of depression as something that is meaningful.
Dr Rupy: Yeah, yeah, yeah. So with the systematic review, talk us through that that process. How did you do it? Who did you collaborate with?
Joanna Moncrieff: So a system the main point of a systematic review is that you take a systematic approach to identifying the the studies that you're going to look at. So so I got so so I realised there was going to be a lot of a lot of literature out there to look at. So I I got a team together of colleagues who who had some of whom had experience of doing systematic reviews in the past and other people were just available to help out. And and we identified all the main areas of that have been main areas of research that have been done over the last few decades and divided them up between us and we came up with search terms and and um looked through the main medical databases to identify all the different studies that have been done in these areas. Now, we did what's called an umbrella review because there was so much research that that we weren't able to look at all the primary studies. So what we did is we looked at the reviews that have already been done. So the reviews that have already been done in each area that have already put the studies in each area together. So it's like a sort of meta review. So we systematically identified all the all the meta reviews in all all the different areas that we'd that we'd demonstrated were were active areas of research into serotonin and depression. And and then we looked at those reviews in detail, we analysed their quality, extracted the data that that that was showing effects and and then and then summarised our findings in in each area. That's essentially what we did.
Dr Rupy: And so you were looking at some of these studies that we just mentioned here, the the the studies where they look at cerebrospinal fluid with serotonin breakdown products, the tryptophan depletion studies.
Joanna Moncrieff: Yes, so they're they're a slightly different sort of study. Instead of comparing people with depression and people without depression, these are studies that take people who don't have depression to begin with and then they give them a special drink that reduces the levels of serotonin in the brain or is thought to and then then people's mood is measured and so it's a test of whether lowering serotonin can induce a depressive state. And those studies have been have been conducted mainly in people without a history of depression, but there have have been some in people with a history of depression. The hypothesis of these studies was of course that lowering the serotonin would make people depressed. Actually there's no evidence that it does so in people who don't have depression to begin with.
Dr Rupy: Got you. Okay. And again, the serotonin transporter studies, the genetic studies, all the ones that we just mentioned here, inconclusive or no evidence.
Joanna Moncrieff: Yeah, yeah. The the genetic studies were interesting because they show a pattern that I think is is is a common pattern in research. Early on there were positive findings and people got very excited that the the gene for the serotonin transporter might predict someone's risk of getting depression later in life. Then the evidence didn't seem to be that supportive of that. So then people thought maybe there's an interaction between that gene and adverse life events. So there was a lot of research looking at that. And again there were studies that suggested that might be the case. Over the last few years there have been very large, very high quality studies of the serotonin transporter gene and and these are possible because there are these huge data banks of genetic samples. And those have showed showed unequivocally that there is no effect of the gene and no effect and no interaction between the gene and adverse life events on the risk of depression, but having adverse life events does increase your risk of depression on its own.
Dr Rupy: Okay. So something that we recognised before but when you put serotonin into the mix, it there's nothing there.
Joanna Moncrieff: It doesn't make any difference. Yeah, yeah. But it's just interesting that those those studies show this clear pattern of early studies when there's a lot of sort of enthusiasm and maybe the studies are a bit small and not being done that well, um show positive results and as the you know, as time goes by and the studies get bigger and better, those positive results fade away.
Dr Rupy: I find it wild. Absolutely wild. I mean, I went to medical school in the early 2000s and became a GP. I can hear in my my head the conversations that I've had with patients where I've repeated the there's a chemical imbalance in your brain, these medications can increase that. There are a lot potential side effects here, you need to be on them for at least six months, you can't just stop them, you we've got to see you regularly. You know, it's Yeah. It's it when I read the book and I went through the study and I read about the history of it, it was it I it left me with a real pit in my stomach for the for the number of consults where I've used that terminology unknowingly. And it's you know, it's it's embarrassing, I think, for a lot of doctors it will be.
Joanna Moncrieff: Yeah, yeah. Yeah, I mean it turns out it was a house of cards. I think it was difficult for people to see because there is so much research going on into serotonin and depression and all sorts of other possible biological mechanisms and brain chemicals. So it was difficult to see that there was nothing there because there were just so many studies and just the fact that there are lots of studies going on sort of creates the impression that there might be something there. And I think this is this is why I felt there was a need to get this research together and really make a definitive judgment on the evidence.
Dr Rupy: Yeah, yeah. And so this paper comes out 2022. I imagine, you know, you've done a thorough review, it's been accepted into which journal was it?
Joanna Moncrieff: Molecular Psychiatry, which is part of the Nature journals.
Dr Rupy: Yeah, so reputable journal, top tier journal. Um just talk us through the response to this because you're not I don't think you're saying anything particularly controversial in this systematic review other than the chemical imbalance theory that we've been repeating, you know, in pamphlets and on websites of which you've got in your your appendices. Um you know, it's incorrect or there's no basis for it. I don't think that's a particularly controversial statement if there's evidence to state that. So what what what was the reaction of colleagues and and other people in the industry?
Joanna Moncrieff: So I think at least initially most people, as you say, accepted the fact that there's not really evidence for the for for a link between serotonin and depression. But of course the obvious question that that immediately raises in everyone's mind is, well, what on earth are antidepressants doing then? Yeah. So people so psychiatrists around me, um were were okay with with the sort of strict narrow findings of the paper but very nervous about any discussion that led on to the implications for antidepressants and any certainly very nervous about any discussion that suggested that antidepressants might not necessarily be such a great thing. So there was uh so so there were psychiatrists who who who basically tried to I think to sort of quieten down the discussion and who came out when the paper was published saying, oh you know, this isn't important, you know, we shouldn't be we shouldn't be really discussing this or taking any notice because we've known this for years, you know, we know that there's no uh we know that the chemical imbalance idea hasn't been demonstrated and what's important is that antidepressants work and and people shouldn't, you know, lose their confidence in them. So that was one of the main main responses to the paper.
Dr Rupy: Okay. And was there criticism of the actual paper and the way it was conducted that um was valid or useful or?
Joanna Moncrieff: So so so later on, so the initial reaction from from um from psychiatrists was or from sort of mainstream leading psychiatrists was, oh we knew this all along, it's not important. Um but then a few months down the line a group of psychiatrists got together to criticise the review and to suggest that we hadn't done it very well. They suggested for example that we'd missed studies which in fact we hadn't missed. They suggested that uh we'd um we'd included studies that we hadn't that we shouldn't have done according to our inclusion criteria which we hadn't. So so they they were they were trying to sling mud, I think at the review to to get people to uh lose confidence in it. They made a lot of mostly trivial criticisms of of the paper and and most of them were inaccurate anyway. Uh and the the majority of their criticism was on how we'd rated the certainty of the findings, which is always a subjective activity. We'd only added that in sort of in the later stages of doing the review because it sort of been increasingly accepted as as an important part of doing a review. When we started off, not many not many reviews did that. Uh and and and yes, you you know, you can argue that we could have rated the certainty of our findings a little bit differently, but it doesn't nothing that they said substantially changes the conclusions of our review.
Dr Rupy: Okay.
Joanna Moncrieff: What they were also saying was, well, there is some evidence for links between antidepressants and links between depression and serotonin, but of course we weren't denying that there was some evidence, we were just saying that there is not consistent evidence and that there's other evidence that is negative or contradictory.
Dr Rupy: Yeah, yeah. And then there are other theories of a biological mechanism behind depression as well that are perhaps well, they're less substantiated as I've learned from the book, but I guess there are other avenues that people can use if they're wedded to the idea that it's a biological issue.
Joanna Moncrieff: Yes, well well that was another response of of of psychiatrists and some people in the medical profession was, okay, well maybe it's not serotonin, but there are, you know, there are other biological mechanisms. It could be inflammation, it could be neuroplasticity, it could be glutamate, you know, there are lots of other theories flying around. But as you say, as I point out in the book, there is even less substantiation of any of those theories than there is for the serotonin theory of depression.
Dr Rupy: Yeah. Okay. Um I mean it's interesting that they were trying quite hard to sling mud at the study when everyone had supposedly accepted that the chemical imbalance theory was was unshaky ground anyway. So.
Joanna Moncrieff: I mean on the one hand they were saying they were saying, oh we we've known this all along, this is not news, this isn't interesting, don't take any notice. And then the other on the other hand they were saying, oh but but serotonin does have a role in depression, you know, trying to defend it. I mean it was completely contradictory.
Dr Rupy: It's a it's a very weird scenario. Um okay, so would you accept that there are certain elements of their critique that may hold value like the certainty factor for example, um.
Joanna Moncrieff: Well, in any review there are lots of decisions that could be made differently. For sure. Um so uh so yes, we could have done different certainty ratings. Um but but I think overall it was a good quality review. I would defend the quality of our review and actually the the evidence that they pointed to was much worse quality than than what we'd done. So so just on the certainty ratings for example, we had rated areas as having greater certainty where there were bigger studies. So for example, you know, the genetic studies where you've got over 100,000 people in in some studies. And they questioned whether we should give more credence to areas where there were very large numbers of people and I would say I would suggest that it's fairly obvious that that you know, areas of research where you've got huge studies are going to be more reliable than areas where you've got very small studies.
Dr Rupy: Yeah, I mean, simple statistics really. Let let's talk about the the the more uncomfortable and you've already alluded to it already. Um some people will say, yeah, I get it, chemical imbalance doesn't really hold up. It's a hypothesis, but does it really matter if I'm on antidepressants and they work and there's clear evidence that they work?
Joanna Moncrieff: Yeah. Yes, so obviously this is a really important question and and um to be fair to the people who attacked us um after the publication of the paper, I think one of their concerns was some of them were concerned that people might throw away their antidepressants and you know, then get into trouble with withdrawal symptoms, which is a legitimate concern, or that people with depression wouldn't come forward for help. And obviously that can be a concern too. So so you know, I do recognise that that there were some legitimate concerns. Um but the but this idea that antidepressants just work and it doesn't matter how they work, I would challenge. On the one hand, we've got this idea that depression is a biological condition, a serotonin imbalance or some other sort of biological problem and that the drugs are working by rectifying that, by rectifying some abnormality in your brain. On the other hand, we've got the idea that antidepressants might be well, either just having a placebo effect and or working maybe a bit like the benzodiazepines, not zonking people out in quite the same way as benzodiazepines, but maybe numbing people a bit. And there is research that shows that antidepressants cause emotional numbing. It's very consistently reported by people taking antidepressants for depression but also for other conditions and there is a volunteer study as well showing this now. So whether antidepressants work by numbing your emotions or targeting some underlying biological abnormality, it seems to me are very different situations and that people might make different decisions if they are given, you know, given those different alternative ways of of understanding antidepressants. So if people are told, you know, we have incontrovertible evidence that you've got something wrong with your brain and these drugs are going to take it right, are going to put it right, of course it makes sense in most circumstances to to take the medication. But if you're told we don't know what's going on in your brain if or if there is anything that is specifically related to your, you know, your your mood and your feelings that's going on at the moment, we've got these drugs that um change your normal brain chemistry in some ways. Um and therefore they change your consciousness in more or less subtle ways. One of the effects they seem to have is this emotional numbing effect. Some people might say, yes, that sounds great, I'd like to be a bit numb, but some people I think would say, no, that doesn't, you know, that's not what I'm looking for. And actually most people I would say find those emotional numbing effects quite unpleasant. Um so I I think it's I think it's very important how we think about antidepressants working and very important that we don't misinform people or allow people to labour under misapprehensions, misunderstandings about what antidepressants are doing.
Dr Rupy: Okay. If I was to take the perspective of a skeptic and actually make the case that antidepressants are working and we have incontrovertible evidence regardless of the chemical imbalance theory that they work, we've done randomised control trials, we've demonstrated a positive effect when people take these antidepressants, what holes would you pick in my argument for the idea that the studies that we have demonstrate regardless of the mechanism that antidepressants like SSRIs and SNRIs are working?
Joanna Moncrieff: So the evidence base, the evidence for the suggestion that antidepressants work consists of these randomised control trials where you recruit a lot a number of people who have a diagnosis of depression and you randomise them either to have an antidepressant or to have a placebo substance. If you put all the and there have been hundreds and hundreds of these studies done over the years, many of them conducted by the pharmaceutical industry. When you put all those all those trials together or all the ones that where the data has been published or where we have access to the data together, you find that overall the difference between people who take an antidepressant and people who take a placebo is very small. It's usually measured on a depression rating scale. The most commonly used one is called the Hamilton rating scale. That has a maximum score of 52 points and the difference between an antidepressant and a placebo is two points. So it's very small compared to the you know, the maximum score. Um and moreover, that small difference may not be actually be a pharmacological difference or a pharmacological effect because people in these studies can often guess whether they're getting the actual drug or the placebo because they might get some side effects, a dry mouth, a bit of nausea, or because they just feel subtly a bit different. And they can probably particularly guess if they've been on antidepressants before as many people in these trials have been.
Dr Rupy: Right.
Joanna Moncrieff: So people are often able to guess so they're not reliably what we call double blind. These trials are set up so that people people are not supposed to know whether they're getting the placebo or the or the active drug. But actually people can guess and we know that what people guess they're taking has a very strong impact on their outcome. So it's possible.
Dr Rupy: Just to go on to double blind, so just for the listener, that means that both the researcher and the patient have no idea what drug they're taking. So doubly blind, I know one's meant to know. And it it's very common in pharmaceutical practice to have these double blind tests, but you know, it's difficult to compare what we're talking about in the psychiatric field because, you know, if you're taking a statin or an antihypertensive drug, you're less likely to have significant side effects or this numbing effect that can give you an indication that you're on some sort of substance that isn't inert like the placebo.
Joanna Moncrieff: But but also I think the outcome is important. So you know, if you're looking at a statin trial, as you said earlier, what you're measuring is your cholesterol or or the rate of heart attacks. When you're doing a trial of people with depression, you're using these depression measuring scales and you're measuring people's feelings. And one of the reasons we use placebos is because we know that many people when they start a new drug think it's going to benefit them and the and the thought that it's going to benefit you can actually have a positive impact on your outcome, particularly if that outcome is a rating of your mood. Yeah. So that's why the fact that people can often guess what they're getting in depression trials is particularly significant.
Dr Rupy: So this is an amplified placebo effect that can explain potentially, I mean this is we're just speculating here, but it can potentially explain the the marginal improvement in the Hamilton score which is used for depression.
Joanna Moncrieff: Yeah, yes. Yeah. There there is a bit of evidence that that is the case. Um myself and some Australian colleagues did an analysis of some data from a randomised control trial of an antidepressant in children and adolescents and what we showed was that if you if you compare the antidepressant and the placebo without adjusting for whether people have guessed correctly that what they're taking without adjusting for people's guesses, then the antidepressant looks better than the placebo. It's the difference is not quite statistically significant but it is almost. But then if you add into the equation what people guessed they were taking, that difference disappears. Oh wow. So there's no difference. And that's because people could guess more accurately than you would predict by chance whether they were getting the placebo or the antidepressant and the people who guessed they were getting the antidepressant regardless of whether they were getting it or not did better than the people who guessed they were getting the placebo.
Dr Rupy: So with everything that you've said so far, it it's sort of understandable or not understandable, I'm not empathising with a uh like an abusive reaction, but you can understand why members of the profession are like fighting quite deep to protect their integrity given that we've been talking about the chemical imbalance theory and giving uh antidepressants to to people to to treat what is, you know, an epidemic at the moment for decades. Um when you say, you know, things like the antidepressants and the the studies that we have that they work is weak or like non-existent in some of these studies, that's got to provoke a fierce reaction, not just from psychiatrists but from the industry as well.
Joanna Moncrieff: Yeah, yeah. Yeah, I mean 8.7 million people in England alone take antidepressants now. So they are very widely used. And they do have harmful effects. They're not just, you know, they're not just inert placebo tablets. They are active drugs, they are changing our brain chemistry in some ways that that we, you know, don't understand terribly well. And that has consequences. And so you're right, the uncomfortable truth is that we have been prescribing drugs which which have little if any benefit for people, but do have harmful effects. And we have been misrepresenting how they what they are actually doing. Wow. So to come back to the issue of whether they work or not, I I mentioned that I mentioned, you know, that they are active drugs and one of the um emotional effects that they that they seem to have is this emotional blunting effect. So in theory, they might help to reduce acute distress in in someone who is, you know, very upset or in a in a really bad state um because of this emotional numbing effect. But in practice, if you look at the trials, the the difference between the drugs and the placebo is so small that I'm not sure that actually that emotional numbing effect it doesn't seem to me that it's been shown to be useful.
Dr Rupy: And actually let let's assume that um there is a weak effect. Um you know, the improvement in the Hamilton score, whatever other scoring system you want to use is enough to convince a doctor that it's worth a shot. What are the side effects that we need to be aware of and in order for us to make a risk benefit decision?
Joanna Moncrieff: Yeah, yeah, so that's this is a really important point. So common side effects that I would hope people are told about are sexual dysfunction. It's uh that's very well established that SSRIs and anything that affects serotonin causes sexual dysfunction. Antidepressants come from different chemical classes and their effects vary. I should I should say that's that's important to acknowledge too. So um they have different effect or side effect profiles. So some of them will make people feel quite um quite sleepy, but others won't. Most of them I would say make people feel a bit lethargic. Um certainly in the long term there's there's it's recognised that uh probably linked to this emotional numbing effect, they can make people feel a bit apathetic. They cause bleeding problems because serotonin is um the serotonin in the in the platelets is involved in the in the clotting procedure and um uh so if you're giving giving drugs that increase it, it it can increase bleeding time so people can have bleeding problems. Um and there are effects to be aware of if you're taking them if you're pregnant. Two common and significant effects that I think everyone needs to be aware of and maybe haven't hasn't been aware of enough up until now are the dependence problems. So particularly if people end up taking them long term, many people will then experience difficulty coming off them, will have withdrawal problems and some people will find it really difficult to get off them. Different antidepressants seem to have different propensities for causing dependence and withdrawal problems. Some are worse than others in other words. Um the SNRIs like Venlafaxine and Duloxetine and Paroxetine are particularly bad for um for inducing dependence problems. Um so I think the dependence and withdrawal issues are important to highlight. And then I mentioned that sexual dysfunction is is a very common side effect. Some people report that the sexual dysfunction continues after they've stopped taking the antidepressant. We don't know how common this is and it's very difficult to do sort of reliable research on sexual functioning because people are a bit reticent about talking about it and there hasn't been done much research done anyway. Um but it's increasingly being reported and in quite a consistent way that some people are experiencing persistent sexual dysfunction after they've stopped taking the medication. Despite stopping the medication. Despite stopping and sometimes years down the line. Years. Yeah. So that's really important particularly because more and more young people are are going on to antidepressants. Now, there's another concern which is that in younger people, there's some evidence that occasionally, and I don't think this is a very common problem, but it does seem to be does seem to occur sometimes, people can become actually more suicidal and can start having suicidal thoughts and and possibly even self-harming as I say, I don't think this is a very common problem, but it has been shown in randomised control trials to be more common in young people taking antidepressants compared to the people taking in the the placebo in those in those trials. So that's obviously a major worry, particularly in younger people. I don't know why it happens particularly in younger people and not older people, but it it does seem to be a specific effect in that age group. And then I said there are concerns about the use of antidepressants in pregnancy. So antidepressants because they um cause bleeding problems, increase the risk of having a postpartum hemorrhage. They increase the risks of having a small baby and of and of the baby coming early, being premature. And and they and and they produce a withdrawal syndrome in the baby. So when the baby's born, it can have difficulties breathing and feeding and may even need to go into ITU or something like that. So there are those concerns. There's also a bit of research but I would say that, you know, this still this this is not confirmed at all, but there is some research suggesting that the use of antidepressants in pregnancy may be related to an increased risk of problems such as autism or ADHD in children in the children that are born to to the mothers. But as I say, I think that's that research is not necessarily very reliable because people who've taken antidepressants often have lots of other problems and we don't have randomised control trials in pregnant women to to be able to control for those.
Dr Rupy: Got you. So there are potentially lots of other confounders.
Joanna Moncrieff: Yeah, exactly. So this issue of persistent sexual dysfunction, I think is really important given more and more younger people are starting antidepressants and I I I expect that very few of them are aware that this is a possibility. We don't know exactly how common it is, but there was a study conducted recently in Canada and it wasn't particularly looking at this issue, but uh it happened to ask people who who responded whether they had had persistent problems with their sexual functioning after they'd stopped their antidepressant. And 13% of people reported that they had and that compared to only 1% who'd been taking another sort of drug and stopped a different stopped another sort of drug. So that study suggests that possibly having ongoing problems with your sexual functioning when you stop taking an antidepressant could be quite common, could be, you know, as much as one in 10 of of the population. And therefore this is such an important point to get across to people when they're considering starting taking an antidepressant that this is an effect that you know, we know that these drugs cause sexual problems and there's the possibility that those sexual problems actually might continue for months but possibly for years after you stop. And and we can't say that that is a really rare problem. We we don't know but it may might be relatively common.
Dr Rupy: Yeah. I mean two things that come to mind when you say that is A, we definitely need to do more research in this area to determine what the prevalence is of persistent sexual dysfunction. And what what would that mean in like practical terms?
Joanna Moncrieff: Yeah, yes, yes, yes. So so it it can take any form. Um but but but one of one of the one of the most typical symptoms of sexual dysfunction that's associated with SSRIs and SNRI antidepressants is reduced genital sensitivity. So people just can't feel as much and and actually SSRIs have been trialled as a treatment for premature ejaculation. So it's well recognised that they have this effect and that effect can go on after, that's one of the effects that can go on after you've stopped taking the drug and difficulty getting an erection and having an orgasm are other problems. And then the other typical symptom is loss of libido. Now obviously people who are depressed also have a loss of libido, but the loss of libido that people get with antidepressants is very much associated with this decreased genital sensitivity and other sexual problems that they have. And and and these and the and this has been shown in animals as well. So there are animal studies where animals have been given antidepressants, then they've been stopped and it's been shown that even after the antidepressants are stopped, they are less sexually active than animals that were given a placebo treatment.
Dr Rupy: Which persists after the treatment stopped.
Joanna Moncrieff: Yeah, yeah, yeah. So gosh. So so it's definitely there's definitely a real effect there and and the people that report this are absolutely devastated by it as you can imagine. You know, they're often young people, they've taken antidepressants in good faith with no knowledge that this might happen. Uh some of them have had sexual many of them have had sexual problems on the drug but you know, expected that these would go away when they stopped taking the drug, have stopped taking the drug and the problems have persisted. Uh it's affected their, you know, in many cases destroyed their relationships and prevented them from forming new relationships. And you know, our our sexuality is such an a fundamental part of what we are, isn't it? I I think people feel really changed by it and it's often also accompanied by um by by the emotional numbing effect. So people often feel sexually and emotionally numbed.
Dr Rupy: Yeah. With the rise of the number of younger people being diagnosed with depression and hence being offered a medication, again, you know, it really it's really important for them to be aware of these potential side effects because it can have devastating consequences on fertility and yeah.
Joanna Moncrieff: Yeah, absolutely. I remember one person saying that um you know, they couldn't couldn't just didn't have the motivation to to get back into a relationship and they couldn't even enjoy music anymore because of this sort of emotional numbing effect.
Dr Rupy: Yeah. I just want to dive into the dependence and withdrawal element here because when these drugs were released into the market, I remember you saying and in the book as well, they were sold as non-dependent, you know, non-addictive substances that were really safe and they work. Why?
Joanna Moncrieff: That was the the um the campaigns, the disease awareness campaigns that were run in the 1990s to um to try and alert people to the problem of depression and um encourage people to go and see doctors and get treatment for their depression very much highlighted that uh claimed that antidepressants didn't cause addiction or dependence problems. Now, antidepressants I I think one of the reasons for that is that we have this idea that dependence is only is only a problem when you've got a drug that people like. So we can get dependent on alcohol or heroin or Valium, um but you're not going to get dependent on something that that doesn't give you a buzz of some sort. Um but it turns out that you can. Antidepressants don't make people feel very good. They're not the sort of drugs that people want to go out and buy or score. Um or abuse. Uh but they do they do cause withdrawal symptoms when people try to stop them, particularly if they've been using them long term. And we did actually know that from the benzodiazepines as we were saying earlier, people had um withdrawal symptoms from benzodiazepines even when they'd been using them just as the doctor prescribed, you know, hadn't increased their dose or messed about with them at all. It was just that they'd continued to use them over a long period.
Dr Rupy: So I mean it it's amazing to me that we've got to this position in 2026 where we still have the chemical imbalance theory lurking around. In your appendix, you know, there are still people putting this on websites and and you know, some reputable government websites as well. Um and this idea that antidepressants are non-addictive and um and they generally and they are work and they're worth it. Just talk us through the pharmaceutical spin that had to be involved for us to to to keep like hold of these ideas for this long. It's been over 35 years now since they were first released.
Joanna Moncrieff: Yeah, so so the first wave of marketing was in the early 90s when the first SSRIs were introduced. So that would be drugs like Prozac, for example. And then further SSRIs were released and and marketed during the 1990s including Sertraline. And then from the 2000s, the SNRIs are introduced, that's drugs like Venlafaxine and Duloxetine. So that means there's a whole new wave of marketing to market them and they were marketed as correcting an underlying imbalance of serotonin and noradrenaline. And noradrenaline had been proposed as as being abnormal in depression back in the 1960s but people had already concluded by the 1970s that there was no evidence that it was abnormal in people with depression. So I I think the reason it's been sustained is that there've been these renewed waves of marketing with new drugs being released and and you know, this marketing was was really intensive. These drugs became bestsellers. Prozac was on the cover of Time magazine and all these famous, you know, US magazines. It won an award for being drug of the year in 1994. I didn't realise you could get a drug of the year award. I know, nor did I. Um so you know, they they've been big blockbuster drugs with obviously millions and millions of dollars and pounds and everything else put into their marketing to ensure that uh that people get the message about them. So you know, so marketing I I think is one of the reasons that we've still got this idea and why it's been so influential. The other reason is because there is an element of the medical profession that that likes it and particularly um of the psychiatric profession, the psychiatric branch of the medical profession, and that is because, you know, depression is is the bread and butter of psychiatry, I suppose. It's such a it's such a common condition and I think there's a worry that if psychiatrists admitted that this, you know, we we don't have any evidence that this is actually a medical problem in the sense of being a biological bodily problem or originating in in a bodily mechanism, that they would feel they didn't have a role. Um and then I think another reason why it's stuck around, well two reasons, one is it's simple and two is it's immediately appealing. Um you know, if it was the case that it was that, you know, that straightforward, it was just this one, you know, abnormality in this one chemical and we did have a drug that could just put it right, then you know, then then then maybe we should maybe we should embrace that situation but uh but of course it isn't that simple.
Dr Rupy: Yeah. I mean, if you don't have antidepressants, then what do we how do we treat depression? Like how what what is the genesis of depression in your perspective and and how do you feel we should be better managing this this disease?
Joanna Moncrieff: So I think that the way that we approach depression at the moment is is wrong. In in we we we treat depression as if it is the same thing in everyone who has it, as if we're treating pneumonia or asthma or something like that. I would say that we need to understand depression as the way that human beings react to their circumstances. Maybe not always, but usually I would say depression is a reaction to something that's going wrong in your life now or has gone wrong in the past or something that you're worried about in the future. And so the first the first thing to to do to treat depression, to help people with depression is to help people identify what that is and how they can change that for the better. We can see depression I think as a signal, a signal that there's something in our lives that we are not happy with and we need to change. And of course that's it's not always easy to identify what that is and it's not always easy to change it. So I'm not saying that this you know, is is is straightforward for everyone and I absolutely recognise that people will need help with this process in in um many circumstances. But I think I think if we understand depression like that, it makes us think differently and it makes us think how can we help this individual to to address their particular problems rather than how can we treat their brain mechanism.
Dr Rupy: And and in that light, so if you've got someone who's listening to this and they try and analyse their life circumstances and they should on paper be happy. I I I've got healthy kids for example, I you know, uh I'm in a good job, I'm in a stable marriage, but I just feel low and I and I I I can't help it and the doctor gave me these antidepressants and I feel much I feel normal again. I feel like my normal self. I know that these antidepressants are working for me and that's that's enough. Like what how would you unpack that for an individual? I'm sure you've you've heard this story many times.
Joanna Moncrieff: Yeah, well well firstly I I'm not in the business of trying to tell people not to take antidepressants. You know, I'm absolutely not. I just want to make sure that people are making informed decisions. And if people are already taking antidepressants, it's really important to think very carefully about whether you want to continue or not and certainly not to make the decision to come off them lightly because if you've been on them for a long time, it may it may be the withdrawal process may be difficult and you know, may take a long time. Not necessarily always, but but that's not uncommon. Um so and and I mean I would say that, you know, I I I work clinically, I see people with depression. I would say the vast majority of people who come in through my door have fairly obvious reasons why they're depressed. Uh but of course there are always people who who feel that there there isn't an obvious reason. Sometimes people can sometimes people benefit from therapy in that situation to explore what the reasons might be. But we are all different and you know, people some people are going to be more prone to depression than other people. Uh some of that probably is a a biological thing to do with your genes um and you know, and the how how your biology has been affected by things that have happened in your past. Um but it's not the sort of biological thing that we're going to be able to fix or tweak, I would suggest. So I think in that situation something like CBT might be helpful to help people to manage their, you know, learn to manage their mood as best they can. And then there are things that people can do that generally lift people's moods like exercise. Exercise has been shown in a lot of studies to be really good for mood, for people with depression and anxiety and uh and and and also been shown to be as good as if not better than antidepressants. Yeah. So exercise is definitely something that I would recommend to people. And then I think if we there there was a book that was published recently that I was reading about, um can't remember where now, called Mattering. I think if we if we take a sort of more philosophical approach to to depression, to uh to understanding what makes us tick, what makes us want to go on in life, one of the important things is having purpose and feeling that we matter and feeling that what we do makes some difference and is of some value in the world. And I think that, you know, I I think finding purpose is is something that's that's really helpful for people.
Dr Rupy: Yeah, absolutely. And you know, if there's someone listening to this and they have some of those side effects, you know, the 70 million plus people on well, the 70 million prescriptions I believe in the UK um every year, what would the process of de-prescribing actually look like? You know, if if we were all to collectively decide that okay, antidepressants may not be the best first step and actually we should be looking to get some people off them if they're not feeling well. How do we actually go about that process of de-prescribing?
Joanna Moncrieff: Yeah, yeah. So so part of the process is is to is to try and stop the initiation of antidepressants as well and and try and direct people in, you know, send people in different directions, try different approaches with people. For people who are already on antidepressants and would like to try coming off them, particularly people who've been on them for a long time, I would suggest to make a cautious reduction to start with, maybe reduce your dose by about 10%. If and and and leave that for a couple of weeks. If that's okay, if you're okay with that reduction, you could continue at about the same rate, so making 10% reduction continuing to make 10% reductions um and and until you and and if you reduce in a a percentage way, if you reduce the same percentage of your dose, you'll be reducing by smaller amounts as you go down and it's it's generally been found to be the case that the lower lower doses have the largest effect. So um so when you get down to lower doses then you need to take it then you may need to take the process more slowly. It's very individual, I would say. It does depend on on the type of antidepressant and the amount of time people have been on it. Um so I think just going slowly and and being careful uh and and preferably, you know, having the support of your GP and other any other clinicians that you're involved with.
Dr Rupy: Yeah.
Joanna Moncrieff: Another issue that that some people have to deal with is, you know, if you've been on this this medication for a long time and it's been numbing your emotions, you will get those emotions back. Um sometimes if people stop their antidepressants suddenly, they get a big sort of surge of emotions, almost like a sort of rebound effect and that can be quite difficult to to deal with, to manage. So you know, some of the um withdrawal symptoms of antidepressants include things like anxiety and tearfulness and irritability and I think these are these are signs of that emotional numbing effect sort of being taken away and the emotions bounding up back again.
Dr Rupy: And some people could interpret that as a relapse of their depression.
Joanna Moncrieff: Yes, yes, exactly, exactly. So that often happens. So uh so people start trying to come off their antidepressants, get some withdrawal effects, assume that they're having a relapse and go back onto their medication and then assume that they'll never be able to come off it again. So it's important for patients and doctors to be aware that some of the withdrawal effects of antidepressants are emotional symptoms and doesn't necessarily mean that the depression or anxiety or underlying problem is is just coming back.
Dr Rupy: Are there clear de-prescribing guidelines for doctors?
Joanna Moncrieff: So there's a colleague of mine, Dr. Mark Horowitz, who um was a a co-author on the serotonin paper, has written the Maudsley de-prescribing guidelines. So it's a it's a big it's a big volume. A lot of small print in there and very dense. Um but but that that gives instructions for uh for safe de-prescribing for antidepressants, benzodiazepines, Z drugs and the um the gabapentinoid drugs that are commonly prescribed for anxiety as well, pregabalin and gabapentin.
Dr Rupy: Yeah. This might seem like a stupid question, but do you prescribe antidepressants ever?
Joanna Moncrieff: So so I do, I do. I mean I feel that if someone is in the sort of situation where other doctors would prescribe them antidepressants, it wouldn't be fair to deprive them of them. Um so I will uh present antidepressants as an option, um and go through the pros and cons. I will explain my view of the evidence about how they work and what and what people need to know about that and obviously talk to people about side effects and and persistent side effects and dependence problems. And then if people are still very keen to try antidepressants, I I will help them to initiate one. Most often people come to me and they're already taking antidepressants.
Dr Rupy: Yeah, yeah. I mean, I think it's this issue of informed consent which is central to your book. You know, your book isn't anti-pharma in any way. I think it's anti the fraudulent activities of pharma and being more aware of their undue influence, but I don't think it it should be perceived as something that is trying to suggest that people stay clear of any medications for psychiatric illness at all.
Joanna Moncrieff: No, it's definitely not. And I mean I also work with people with severe psychiatric disorders like, you know, they've been diagnosed with schizophrenia or some sort of psychotic disorder and I I prescribe people antipsychotics in that situation which I think are helpful in dampening down their psychotic symptoms. They don't work in everyone, but they do work in some people effectively enough that people can carry on with their lives. So I'm not against the use of drugs for mental health problems. But I would say that I think in general, using drugs for emotional problems like anxiety and depression is is not the best way of of addressing those problems and if people can find alternative ways, that's that's usually going to be better for them.
Dr Rupy: Yeah. Do you see a parallel with any other drugs in today's market that are using similar tactics of the pharmaceutical industry to perhaps inflate the benefits of a medication versus and downplay the negative effects? It's quite a wide question.
Joanna Moncrieff: Yeah, yeah, I mean I mean I'm I'm I'm not an expert so so I I hesitate to to pontificate here. But I mean statins are very widely used, aren't they? And you know, I I I don't know enough about the evidence base to to be to be able to make confident confident pronouncements, but I would wonder whether they're really benefiting everyone who's taking them. Um and then of course we've got the obesity drugs at the moment which I you know, there's lots of debate, debate isn't there for and against, but that's uh obviously there's a huge demand for them and and I'm not sure whether we know everything about the long term the the consequences of people using them long term, whether we know enough about that. And HRT of course, HRT, you know, has a a long complicated history, but it seems to me it's really come back into vogue at the moment. I don't know whether that's that's through the pharmaceutical industry or or just medical professionals promoting it. And again, I think that we are that that there is a sort of tendency to suggest that that this is a free lunch, that you know, that that there's no reason not to take it and that you know, more or less everyone would be better off if they were taking HRT and I as I say, I'm not an expert, but I'm I think that's rarely the case.
Dr Rupy: I think I think there's I agree. I think there's um there's two things I want people to take away from this conversation. Um I mean lots of takeaways. One is to look through the lens of informed consent when taking any medication. And I think you've summed that up beautifully in at the end of the book where it's up to the individual to make the decisions as to whether antidepressants are going to be useful for them. But I think the blanket rule of this is how they work and they they're very effective, um I think that needs to be quashed and I think we need to really appreciate the potential downsides and the the the vast number of side effects there are with any any medication but particularly these. I think the other takeaway is whenever there is a drug that's being painted on the front of Time magazine or being positioned as like a blockbuster that is going to revolutionise whatever it might be. And I think uh GLP ones and the other generations of anti-obesity drugs are having that moment at the moment, you know, you want to look at it with a raised eyebrow. Because there's definitely an underpinning of pharmaceutical play here and everything that I've learned about in your book and some others around the nefarious actions of pharmaceutical companies just makes me wonder and it's the same with the supplement industry as well whenever there is a supplement that is getting a lot of attention for some reason, you know, you really want to be cautious about it and actually take that informed approach.
Joanna Moncrieff: Yeah, yeah, absolutely, absolutely. I I think I mean the the the sad thing is that people have not been able to, you know, make fully informed get give fully informed make fully informed decisions about whether to take antidepressants because they've been given misinformation which has originated from these marketing campaigns.
Dr Rupy: Yeah, yeah. Joanna, I absolutely loved your book. It is wild to me. It should be, you know, a multi-bestseller. I really hope we can amplify your work and I look forward to what you're working on next. Can you give us any indication of what you're working on at the moment? You said you're doing a paper but maybe you want to keep that under wraps for now.
Joanna Moncrieff: Well well I just just had a paper published which is it relates to this, so I'll mention that. We we did a survey of people attending uh the NHS therapy services who were also taking antidepressants and we asked them whether they thought their depression or anxiety was related to a problem in their brain or a chemical imbalance or whether they thought it was due to life events. And people who thought that they had some chemical imbalance or some other brain problem were more likely to take antidepressants for longer, less likely to have tried to stop their antidepressants and more likely to feel that they couldn't cope without their antidepressants. So so that was interesting and you know, I think just shows how this idea that we've been, you know, promoting and and presenting to people that depression is a chemical imbalance, depression is in your brain is is an idea that paints a really bleak picture actually, you know, can make people really pessimistic about their future and and you know, give people the idea that there's nothing that they can do.
Dr Rupy: Yeah. Appreciate your work, Joanna. This has been awesome and uh I hope to have you back on at some point in the future.
Joanna Moncrieff: Lovely. It's been lovely to talk to you. Thank you.
Dr Rupy: Thank you.
