E104 - Deprescribing Anti-Depressants and Challenging "Biological Depression" (w/ Dr. Mark Horowitz)

Mark Horowitz is a training psychiatrist, now working as a Clinical Research Fellow at UCL. He is an Associate Editor of the journal Therapeutic Advances in Psychopharmacology and has edited a collection of papers in the journal on Discontinuing PsychiatricMedication. He has a PhD in psychopharmacology and the neurobiology of depression from the Institute of Psychiatry, Psychology and Neuroscience at King’s College London. He also co-wrote the Maudsley Deprescribing guidelines.

Mark has his own blog https://markhorowitz.org/ and has written in the media about his own personal experiences with antidepressant withdrawal syndrome.

Today we discuss:

• The problems with viewing depression primarily through a biomedical lens 
• The causes of depression
• The limitations of anti-depressants, the risks of withdrawal symptoms when stopping them and Mark’s own personal experiences with this
• Some useful principles in how to wean off psychiatric medications safely if you are considering doing so

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

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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Transcript

 Welcome back to the podcast. I hope everyone is doing well in the run up to Christmas. Today I'm in conversation with doctor Mark Horowitz marks the training psychiatrist. Now working as a clinical research fellow at UCL, is an associate editor of the Journal of Therapeutic Advances in Psychopharmacology, and he's edited a collection of papers about discontinuing psychotropic Atopic medication. He has a PhD in Psychopharmacology and Neurobiology of depression from the Institute of Psychiatry, Psychology and Neuroscience at King's. Mark has an interest in rational prescribing and safely coming off psychiatric medication, which has been the focus of his most recent work, published in The Lancet in Jama psychiatry and the British Journal of Psychiatry, as well as the Schizophrenia Bulletin. And he also co-wrote the Maudsley Deeper Scribing Guidelines, a guide for clinicians about slowly helping patients come off various kinds of drugs like antidepressants, benzodiazepines, and so on. He has his own blog, Marc horowitz.org, and he's written in the media about his own personal experiences with antidepressant withdrawal syndrome, something he personally experienced when he tried to come off antidepressants himself and experience some quite serious side effects. Today, we talk about the problems of viewing depression primarily through a biomedical lens, as opposed to a more psychosocial lens. The causes of depression, the limitations of antidepressants, and those risks of withdrawal symptoms I just mentioned when stopping antidepressants, we talk about Marc's own personal experiences with this, and Marc outline some useful principles as to how to wean off psychiatric medication safely. Some caveats this conversation. Nothing in this podcast should be taken as direct clinical advice to anyone listening, as everyone's situation is unique. If you are taking psychiatric medication and you're considering stopping it, I would highly recommend discussing this with your prescriber in order to make a plan about doing it safely. I do suspect that Marc and I might disagree slightly in terms of the potential value of medications, at least in the short to medium term. But that being said, as I mentioned in the podcast, much of what he says and his research does match with my clinical experience. So I definitely think it's a point of view that needs to be taken quite seriously. If listeners want to learn more, I would also direct them to a podcast episode I made earlier this year in April, which is called My Thoughts on Psychiatric Medications, where I outline 7 or 8 principles to use psychiatric medications more safely. And that's a guide both for prescribers and for patients. If you want to learn more about Mark's work, you can find out more from the website I mentioned. Again, that's Mark horowitz.org. In addition, as I've mentioned recently, I'm doing more talks for companies and organizations, talks about men's mental health, but also psychotherapy in general and other interesting and useful aspects of psychology like personality theory. If you'd like me to talk for your company, team or organization, you can email me at Thinking Mind podcast@gmail.com and put Speaking Inquiry in the subject line, and I'll get back to you as soon as I can. Thank you very much for listening. And now here's today's conversation with Doctor Marc Horowitz. Thank you so much for joining me. Thanks for having me on. We're going to talk about a few important topics today. Depression, antidepressants, perhaps on the dangers of antidepressants and the dangers of coming off antidepressants. Describing. But first, I wonder if you could give us a little insight into your story and how you started to research all of these topics. So I, I guess I can I became interested in how hard it is to stop antidepressants after I had a very difficult time coming off my medication myself. Um, I'm originally from Australia, but I moved to London to a PhD in how antidepressants work and the Neurobiology of Depression at King's College London. Um, when I was finishing up my PhD in 2015, um, I read an article about withdrawal effects from antidepressants, and I found that quite startling because I hadn't been taught that with withdrawal effects from the presence of curves. Um, in my previous training, um, and I guess I had two main thoughts. One, um, you know, I had myself been on an antidepressant at that point for more than ten years. I thought drugs that cause withdrawal also caused tolerance. There was the flipside to the same coin. The more accustomed you become to a drug, the more you get withdrawal from it. So I thought, what is a drug that causes tolerance doing after being on it for more than ten years? And the second issue I thought is that drugs that cause withdrawal effects often have all sorts of other, um, negative effects on people drugs like Valium or Xanax, alprazolam, OxyContin, opioids. And so I wondered what, um, the drug was doing. I already had concerns that I had a number of significant side effects to the drug. Um, I had a lot of issues with daytime fatigue, with concentration and memory problems that I had had diagnosed as various other disorders, including chronic fatigue syndrome and narcolepsy. But I had a vague idea that maybe it's related to, uh, the drug I'd been taking then for many years, which was citalopram or Lexapro. And so reading about this article was a bit of a trigger for me to decide to try to come off the drug. And what I did was I read being a very dutiful, nerdy PhD student, I went and read all the published papers about how to come off antidepressants, and I basically had the same message that coming off these drugs was pretty easy. There are brief and mild symptoms on stopping, and you can do so by halving the drug over a couple of weeks, then halving again before stopping it. Um, some of those articles are written by the professors I was working with at, um, psychiatry. I recognize lots of the names, of course, of the authors. And then I also went and checked on Google because I'm I'm a millennial, albeit a geriatric millennial these days. Um, and there was a very different story on, on, on online um groups where people said it was extremely difficult to stop antidepressants. It took them months and sometimes years. They were grinding up tablets to make liquid versions of the drug and using small syringes to make reductions. They were opening up capsules to count out beads and people that came off these drugs quickly over a few weeks, like doctors often recommend, ended up having severe withdrawal effects, sometimes being bedbound, losing jobs, becoming extremely, um, disabled from it. And I was a bit confused at that point because I'm a I'm a fairly institutionalized person. I've got six academic degrees. I'm used to listening to what professors say. So I was a bit unsure about what direction to take, and I kind of decided to split the difference and go somewhere in between those, those ideas. So I went a lot slower than four weeks. Like the guidelines said at the time, the nice guidelines, but not as slowly as people around I read about went and I basically came off my drug or down to very low doses over about four months. I used a liquid version of my drug, and I used a micro pipette from, uh, the lab that I was working in at the time. So I was lucky that I had access to a cutting edge molecular biology lab, unlike a lot of other people. When I got down to a milligram of citalopram or Lexapro by life basically imploded. At that point, I had trouble sleeping. I would wake up in the mornings in full blown panic, like I was being chased by a wild animal standing on the edge of a cliff. And that side of panic would last for about 9 or 10 hours of the day. I get a bit of relief in the evenings. I started running a lot to get a bit of relief from my symptoms, and I ran basically onto my my feet blades. Um, I felt a bit dizzy all the time, and I and things around me appeared sort of unreal, a bit dreamlike. I should say, you know, none of those symptoms were anything like the issues that put me on the drug in the first place. I'm, um, you know, I went on the drug at 21. I was a in third year medical school. I was a I was an unhappy young man, unsure about what to do with my life. Um, I had all sorts of existential concerns. I was certainly miserable, but I never had the sort of issues, the panic attacks, the trouble sleeping that I had when I came off the drugs. You know, it was if what I had been, I was on the drugs when I went on the drugs originally was three out of ten. What I had when I came off the drugs is more like ten out of ten. Um, I tried to endure that those symptoms for week after week, um, until eventually I thought, if I, if I keep going like this, I'm not sure I can survive. I, um, I don't think I can keep living like this. Um. And I ended up going back on the drug. Um, I increased my dose slowly back to my original dose, and my symptoms improved over a few weeks, which I which I found out is quite lucky because sometimes the symptoms don't go away so easily after you restart. And I realized at that point that I'm now back on this drug, not because it's useful to me, but because I can't get off the drug. Um, I actually ended up I ended up quitting my job that I was doing at the time at, um, at Slam in South London. Um, and I ended up moving back, actually, to Australia, to my family's house, because I was so shaken by the process. Um, I went back to training for a couple of years in Australia and then to to cut a long story short, I basically decided, um, this is quite ridiculous, really, that, um, well, I should I should say I basically then decided to come off the drug again more slowly. And this time I sort of knew who the experts were. There were these online peer support groups, um, where people who had had very similar experiences to me congregated. You know, I sort of soon found out that it wasn't just me that had these issues. It was I found hundreds of people that had similar issues, and then I found tens of thousands of people. It was huge groups of people that had the same kind of very severe symptoms coming off their drugs. Um, I started to come off again, and this time I went to what I now consider to be the experts, the people on these peer support forums. And I followed the advice there. The advice there was basically to come off at about 10% of your dose every month, so that when you're at 20mg, you come off of two milligrams a month. When you get down to five milligrams, you slow down to 0.5mg per month. And I basically that's now several years ago I started coming off my drugs like that, and it's taken me years to come off my drugs, not just not just weeks. And I guess, um, in coming off my drugs, it's improved a lot of the symptoms that I had when I was on the drugs. Things like daytime fatigue, my memory and concentration issues have all largely resolved, which has been, um, it's very upsetting for me to realize that I'd been taking a drug that had caused me so many health problems for so many years, but very, very relieving that I'm now getting out of that experience. And I guess I sort of thought, getting back to the ridiculous aspect of things that I was getting better advice on how to come off my drugs from online peer support forums than from the sort of top professors in the field. And so I wrote an article about what I'd learned from these, um, peer support forums, combined with some of the neuroimaging data that that I'd come across that showed that extremely small doses of antidepressants have very large effects on the brain. And so it makes sense to go down by very small amounts at the end. And that paper was published in the Labs of Psychiatry now a few years ago. And it slowly led to, um, changes in the guidelines in the UK now spreading around the world a little bit. Um, and so all my work since then has focused on how to help people safely stop, uh, antidepressants and other psychiatric drugs. And it's also led to a bit of a reevaluation of their their safety and their effectiveness, uh, more widely. Wow. That's quite a story. And in the ten years that you were on the antidepressants, was it citalopram? 20mg, I'm assuming I do. I think it was. I think it was about ten or 15 or 15 most of that period. Yeah, yeah. And I assume because this is so common and I see this all the time in my patients you're prescribing doctor didn't check in, do a regular risk benefit analysis to see during a ten year period. Should you remain on the job on the drug or not remain on the drug, anything like that? Yeah. That's right. I just got repeat scripts. I was in Australia for some of that time and in England for some of that time. I got repeat scripts. I think on whatever it is, 3 or 6 monthly repeats. Um, I'm going to say that, you know, I hadn't put together the side effects that I had. I hadn't attributed them to the drugs because it has sort of been in the background for so many years. I never put it together. I should say, um, that a GP in London, actually right next door to the Institute of Psychiatry, did say to me at some point, you see, they're doing quite well. Have you thought about coming off the drugs? Um, and I, I wasn't very happy to hear that. I sort of said to her, um, you know, listen, lady, you know, I'm a I'm a psychiatry trainee. I'm doing a PhD in antidepressants. If I'm doing well, it's probably because of these drugs. It would be very, you know, unwise to come off the drugs. So I sort of bit her head off in the same way that many people bite my head off. Not just, uh, patients, but lots of other academics and psychiatrists. So there was obviously ideas in my head that it was useful for me. Um, so, so I so I should I should give brownie points to that GP who did bring up the issue. It's interesting how we can be captured by a by a story, isn't it? And and as doctors, we often feel we're protected from this because we're ensconced in a certain scientific rationalism, or so we think. And of course, you know, that's not entirely false, but we're still just as vulnerable as anyone is to fall in love with a certain narrative of how things go. And if I could share a quick story around this. I worked at a tertiary centre, meaning a highly specialised clinic national service that sees people from all around the UK with treatment resistant depression. And with the best minds in the country trying to figure out what might be the appropriate way forward for someone with treatment resistant depression. And there was one particular patient who had tried almost every drug you could think of, and they presented a disservice. I, when I was working there, ended up referring this person to a low cost psychotherapy clinic. They had never really had psychotherapy in their lives. They had therapy for something like 30 or £40 a session, and over a 3 to 6 month period, their mood was better than it had been in something like five years. And that's really to me, that's really awakened me to the dangers of hyper focusing on one small part of the story, in this case, what's going on with someone's neurotransmitters and not taking a bird's eye view and thinking, you know, what is going on as a whole for this individual? And what could be the other factors at play in dealing with something like depression or low mood. I mean, it's an interesting story. It's not not at all surprising to me. I hear those stories all the time. I think they're probably more common than the than the opposite. I mean, you know, the way that the the idea that you can fix someone's mood by affecting their neurotransmitters is a bit peculiar, to be honest. Um, you know, I think I've come across a very useful model which you might have heard heard of from Joanna moncrieff about how to understand what drugs do. Um, you know, it's about comparing a drug centred model with a disease centred model. You know, a disease centred model suggests that, you know, um, the psychiatric drugs can reverse the underlying cause of a mental health problem, a little bit like the way that an antibiotic kills the bacteria causing a lung infection and therefore relieves the cough and fever. And, you know, psychiatric drugs are often presented by acting in that way that they can. Fix up the underlying neurotransmitter problems in psychiatric conditions like depression, for example. Um, but of course, a problem with that is we don't know the underlying chemical changes in depression. You know, there was a there was a narrative for a long time which said that depression is caused by a chemical imbalance, which was thought to be something like low serotonin, which most of the public believes or did believe for many years. Um, and that depression can be relieved by taking antidepressants, which increases serotonin in the same way that, you know, insulin can, can can fix up diabetes. Um, you know, I guess on on one level, that hypothesis is false, because if you look at all the studies, there's not a there's not a reduction in serotonin in people with depression versus healthy volunteers. But in a broader sense, you know, I think there's sort of a category error happening in, in looking at why someone is depressed. Um, you know, it's a bit like, um. You know, saying, I thought of using a somewhat simple analogy with a computer. You know, if your software breaks down, you know, Microsoft Word is not not working anymore. Of course, there's something happening in the computer in the in the circuits. But if somebody walked in and they wanted to open up your hard drive and solve all your circuits to fix Microsoft Word, you'd think they're making a category error. They're mistaking the hardware for the software. And, you know, I think the reason why people are depressed and anxious is because of what's going on in their lives. You know, there's childhood, there's the stresses, you know, loss of loved ones, career problems, relationship problems. You know, the research very much strongly backs that up, that then the the greater number of stressful life events you have in a year, the more likely you are to be depressed. And so it's about people's emotional needs, but not being met or about them being overwhelmed by stresses. And yes, of course, you know, I'm not a dualist. Of course, what's happening in the mind, you know, is happening in the brain. But to understand it at the level of the brain, I think is, is is making a category error. So just to bring it back to to. To psychiatric drugs. If psychiatric drugs like antidepressants are not fixing the chemical imbalance underlying depression, what are they doing? You know, there's another way of thinking about how drugs were, which is which is the the drug centered model. Um, and that's sort of the way we would understand lots of recreational drugs. You know, drugs are psychoactive substances that cross the blood brain barrier. They affect the brain, and they affect the way that we think and feel. Um, and a lot of straight drugs, you know, are generally experiences as fun or, or euphoric. And some psychiatric drugs are like benzodiazepines or stimulants, but other ones are not as positive. Um, and so, you know, drug like an antidepressant, generally when you ask people who are on the drug, how does it feel? Most people will say that they feel emotionally numbed, that their range of emotions, from very positive to very negative, has been compressed into the middle. Um, and some people can find that a great relief. So a lot of people will say that their antidepressants were very helpful to them. And I think they're often talking about their emotions being turned down from a, you know, a ten to a three on the volume knob. And if you're experiencing a lot of anxiety or panic or depression that can be released, you can also cause a lot of trouble in the long term. You know, one of the main reasons people come to the describing clinic that I run is because they feel emotionally numb. They don't feel their emotions. They don't know what they think about loved ones. They've lost interest. Um. So I, you know, in this disease centered model, taking a drug for a mental health problem, you know, the drug is not solving the problem. It's kind of superimposing an effect on top of things. And so, you know, an analogy might be drinking alcohol for social anxiety. If you're socially anxious and you drink alcohol, you tend to feel less inhibited and less anxious around other people. Nobody would think that alcohol is reversing the underlying cause of social anxiety. Everyone understands, you know, you're drunk. It's the alcohol being superimposed on your emotions. Nobody thinks that social anxiety is caused by an alcohol deficiency. Um, uh, and I think that psychiatric drugs are probably best understood through that lens. And I think that also brings in other things that the more you use, the longer you psychoactive drugs like psychiatric drugs, the more your brain becomes accustomed to them. So you get tolerance effects when you stop them, you get withdrawal effects because the changes, um, to the drug, uh, persist after they're stopped. And that, like a lot of recreational drugs, drugs can have toxic effects in the long term. And so, for example, for antidepressants, we know they can cause sleep disturbances, memory and, um, concentration disturbances, uh, weight gain, diabetes, emotional numbing, sexual issues, um, which we know, some of which will persist even enough to be able to stop them. So, um, I think that's the, you know, in that lens, you know, can an antidepressant fix someone's misery or their anxiety? I think what it can do is it can often suppress their symptoms in the short term. I think there's there's an increasing literature about tardive dysphoria that taking psychiatric drugs long term can actually lead to worsening moods, you know, which makes a lot of sense when you think about recreational drugs, which if you take them in the short term, are often euphoric and so make you feel good, but in the long term can have negative effects. And so, um, you know, I think the idea of treating someone's misery in their life with drugs is a generally fraught way of approaching things. So I'm not surprised to hear that somebody is, you know, mood was improved by talking through their problems in a structured way to try to make sense of things in a way that bombarding them with drugs, you know, never, never was never successful. I think the I think the whole paradigm is, is somewhat, um, uh, you know, Miss Mis misaligned with what's going on. I'd like to really zoom in on the emotional numbing, emotional blunting issue, because, again, this is something that I never really heard about from my mentors and my training. I it's not listed as a as an official side effect, as far as I know, in the British National Formulary, the BNF, I don't believe it was in the Maudsley guidelines. I was never really warned about it, but anecdotally speaking to many people in my personal life, I've tried antidepressants, speaking to many of my patients. A lot of them report exactly what you say, that the range of emotions narrows, and again, you could see how that could be useful in a crisis temporarily to help someone get through a difficult time. Maybe feeling every feeling might not be a good idea, but one of my main interests is psychotherapy. And in psychotherapy, we kind of talk about how your emotional life is pretty essential and emotions give you really, really important information about the world and about your relationships. It's really important to feel anger and to be able to integrate it, for example, and use it. Even sadness, speaking not of depression, but ordinary sadness is useful to reflect on negative things which are going on in your life, and you can make a kind of tactical retreat from life and then hopefully come back to a bit stronger. Similarly, all the positive emotions love, joy, gratitude, all this is really important and you need to get in touch with them so you can cultivate your emotions and triage them. So of course, having them blunted for a long period of time can really impair people. Um. We've also raised another issue, sort of the hardware versus software issue. And I guess you're primarily making the point that depression is in, in, in light of the evidence largely to psychological and social forces. Do you, however, leave the door open for maybe some pathological routes to depression, which might be biological? Maybe not in most cases, maybe not in the vast majority, but perhaps in some cases. And the reason I say that is because, of course, mental life is, uh, hugely influenced by our physiology. You know, for some reason, for example, if someone's, uh, stops producing thyroid hormone in adequate amounts, they get hypothyroidism, they can become depressed. And I do like to leave the door open to some things which might be going on in the brain, which perhaps we don't even understand yet, which may be causing some some percentage of cases of depression. Do you leave that door open for, for maybe a primary hardware issue, if you like. So maybe I'll come back to the emotional blunting and answer your last question. Um. So I'll put it like this. Um, so first of all, if something is caused by low thyroid hormones, you know, it's not major depressive disorder, it's hypothyroidism. So it's sort of by definition, not not depression. I guess the question is, and this is the question that I looked at for four and a half years in my masters in my PhD is there's something that's more subtle than low thyroid that's causing depression, some sort of, you know, I, I spent hours in, in cell culture clubs looking onto microscopes to see, you know, inflammation, stress hormones, neurogenesis. Is there something, you know, it's less blatant causing it. So that was certainly an idea in my mind for many years. Okay. So I've asked the perfect person. Yeah. And I think overall, you know, I would it's impossible. It's impossible to rule out everything. But in my mind the answer is it would be very, very slim, the chances of that being the cause. And I'll I'll tell you why I think that, um. By the age of 45. Have a guess what proportion of people meet criteria for clinical depression or clinical anxiety? I don't just mean feeling sad or feeling down, I mean MDD, Gad according to the DSM or ICD. Have again, so you're saying what proportion would have met the criteria for this diagnosis at some point in their lives? Exactly, exactly. I would say at least one and four, one and three. So so the answer is 70% of people. So the way that I'm getting this is there's a study where they went every five years to people. They got a group of people, a thousand people born consecutively in a hospital in New Zealand. And they interviewed them every five years, a bit like that documentary Seven Up. They except this time, much less fun. They came in and asked them the diagnostic interview for mental health problems. And by the age of 45, that's where they're up to now. 86% of people met criteria for any mental illness, and most of that was anxiety or depression. So 70% of people by the age of 45 met criteria for an anxiety or depressive disorder. There's just a random group of a thousand people born in the hospital. Um, that's one point. So the first thing to say then is it's extremely common. More of us will meet criteria than won't meet criteria. So the idea that there's something biologically wrong in most people is, is already a bit suspect. Yeah. And I definitely do want to make that point. The point I wanted to make is could there be in a very small percentage of cases, something going wrong biologically, which we don't yet understand? So then then my second part of the answer is people often ask me, so what causes depression if it's not serotonin, what causes it? And I and I, you know, I say, well, I feel like my I feel like your grandma would know in my grandma would know, um, which is, you know, when life is awful, people get depressed in short terms. And that's what the cutting edge research shows. You know, if you look, there's the best researcher in this field is Ken Candler. He's got a famous study where he looks at thousands of people and he's asked them, tell me about what's happened in the last year. And he notes down the number of stressful life events they have. Um, and, uh, you know, just for life event is divorce, job loss, death of a loved one. Um. Major physical illness diagnosis, those kind of things. And he graphs people on the x axis number of stressful life events from none to more than ten and risk of depression. And the relationship is like this incredibly steep line. If you have no stressful life events, your risk of depression is very small, and if you have more than ten, your risk is 30 times that of people that have no stress for life events. The other aspect of it is it's divided into personality types. So there's five different personality types from not neurotic at all to very neurotic. Neurotic basically meaning how sensitive you are to stress. So, you know, maybe Barack Obama is incredibly resilient to stress. And Woody Allen, who maybe means nothing to people these days, or Mr. Bean, I'm not sure what the right British equivalent is, is very sensitive to stress. And so the more sensitive you are to stress, the steeper the line and the less sensitive the the flatter the line. Um, so in personality there is a bit of biology, you know, there is a bit of our genetic heritage. There's also childhood, you know, experiences. And so there is some sensitivity to stress in our biology. So, so people say you don't think any biology at all. No, I think there is there is biology of course, in our response. If you look at the if you look down at the people that have almost no stressful life events, almost nobody is depressed. So this idea out there that was, you know, in textbooks and is around of uncaused depression isn't found in research, you know. Um, if you got to be able to have many stressful life events, you know, a huge proportion of depressed, I should say this relationship between stressful life events and depression is about as strong as relationship between smoking and lung cancer. You know, I, I haven't come across anything that's so strong. So you sort of. And then the third point is every single study that's looked at, um, a biological marker in depression has found nothing. There's a group in Holland did a meta analysis in molecular biology or molecular psychiatry looking at stress hormones, inflammation, neurogenic genes. And it all comes up as null. Neuroimaging null. So you put it all together. Depression is incredibly common. Most of us will experience depression. It relates to the events in our lives, you know, with a very strong gradients. There's been no. You know, gross abnormality found. What makes it more likely? Does it sound like the story of a normal brain responding to life, or an abnormal brain responding to something? You know, and it started life. And I think the overwhelming story is this is a story about normal brains responding to stress in life. So can I rule out 100% some sort of biology? I can, but that overall story is not saying there's some weird, you know, receptor in the brain somewhere that's gone. And this is a story of very commonly for most people, given the right circumstances, they become miserable. The same thing happens to dogs. You know, if you shock dogs, they lie down. If you beat cats, they become depressed. You know, it's almost you know, it's almost a mammalian response to to adversity. So I guess overall, if I had to put my money on it, I put it on being normal brains in stressful circumstances than abnormal brains. Yes. And firstly, it's great to have a chance to go over this evidence with you. And secondly, for me, the concept of learned helplessness comes to mind. So again, learned helplessness is something studied in mammals. It's been studied in dogs. And it essentially means something like no matter what I do, the outcome is the same and it's not the right outcome for me. And when you set things up like that for an individual, and I think many individuals feel like that, it may not be the objective truth. Perhaps they have choices where they're not seeing them. Exactly. Maybe there are changes that could make a lot of the work of psychotherapy, in my opinion, is trying to shift the way people might relate to the different difficult experiences they have in their life. But nevertheless, when they feel that sense of no matter what I do, everything is the same. That's the breeding ground for something like depression. And I would say again, in medical school I was often told about the the potential case of depression where everything is fine, but they're depressed like everything in their life is okay. And in my experience, that hasn't been true, that largely when people are depressed. Exactly. There are at least five good reasons why they might be depressed. And even, you know, people can appear. Things can appear very well for someone on the outside. They might drive a nice car or have a good income, but they might be dealing with some huge existential problem that just isn't obvious to anyone is looking at them. So I would say what you say does corroborate with my clinical experience. Yeah. So I just wanted to jump on that. People always say, what about uncaused depression? What about people who have it all together? And I my response is same as is yours. You know, in 15 years in working in psychiatry, I've never met that person. I've never, ever met someone that hasn't, you know exactly at least five reasons to be depressed. So that is that is my experience as well. I'll just pick up on psychotherapy just for one minute. Yeah. So as people hear me speaking, they think, oh, this is a very big proponent of psychotherapy. You know, I'm, I am interested in psychotherapy. I've been a patient of psychotherapy, I've given some psychotherapy. And I think it's important, but I also think it's worth zooming out. You know, it's often the context of people's lives, you know, social forces like poverty and inequality and racism and insecure jobs, you know, that is not about the way people think about things, but it is an objective reality. So I think that also plays a very big role in why people are miserable. Um, you know, that's that's important not not to leave that out. Yeah. But I what I would say to that is that I think, uh, people can often think of psychotherapy as just changing the way you think about something, and that's part of it. But I actually think it goes a lot deeper than that, that it's changing the way you think, changing the way you relate emotionally, but then ultimately changing the way you might behave and in the short medium and then hopefully long term actually change your life outcomes. So I'm a big believer that when psychotherapy is done well, it does result in a concrete impact to someone's quality of life in the real world, in ways that can be measured practically. And I don't think that just has to apply to things like CBT. That is not to say having said that. And you're not wanting to diminish these very strong social forces. Obviously, poverty, racism, other forms of inequality, war, which we're seeing obviously a huge amount about with Ukraine, Syria, Gaza, Israel right now, you definitely don't want to understate that, but to to within the degree that someone has choices that they can make and has different options, I think psychotherapy can be a very powerful tool to make different choices than they might have made before. I guess I just said that I think that's true about making choices. I'll just say that a lot of those things aren't within people's ability to to to choose to change. So, you know, a lot of exactly as you say, all these social forces, it's not about people making bad decisions or making the wrong decision. They don't have the opportunity. You know, that they can't change some of those large social forces. So but I'm not. But I think I think that definitely has a has a role to play. I agree with you. Yeah. So all of this being said, I mean clinically, how do you think about depression. Is it still a valuable diagnosis for you, a valuable concept? Do you apply it to patients that you see? I think it's got significant limitations because, you know, it takes away from the complexity of, of of of something, you know, people can kill people and become depressed for all sorts of different reasons. And you lump it all in the same box, the same three words, and you go to a, uh, you know, some kind of list of different drugs or treatments or even therapies that sort of one size fits all. I don't think that makes sense. You know, I guess it makes more sense to work out why somebody in that way, you said you come across people with five different reasons. It's good to work out what those five reasons are, so you can try to at least help them see that or to to help them if you can, um, solve those problems. And so I think it's much more sensible, you know, something like formulation, why is this person ended up in this place than to use a diagnosis that doesn't have any biological meaning that we've found or really any kind of, um, prognostic meaning or, or, uh, treatment guidance. So I don't think it's a very useful concept. One thing I did want to mention, actually, is once, you know, obviously depression to most people, I think when most people think of depression, they think of mild to moderate depression. And of course, as psychiatrists, we see more severe forms. And that might be severe. That might include severe psychomotor retardation, which means real slowness, uh, and limitations to one's spontaneous morbidity. They might eat less, drink less to the point of dehydration or starvation. Like this can happen. And how should we understand that? Is it. That the low mood has gotten to the point where then more some biological mechanisms do start to kick in and generate a positive feedback loop. Is that a good way of understanding it, or how do you understand that problem? Uh, look, I'm not sure I've got all the answers here. All I know is that at different points, when I've been depressed, I've been sick and morally retarded. Um, so I would have definitely met the criteria for severe depression I've been prescribed, ect. At different points, I didn't, I didn't, um, I didn't take it, but I was prescribed it. Um, and I guess the thing that's been most useful to me is to make sense of why I was depressed. What? What I guess what emotional needs are not being met. What things in my life were out of out of, um, uh, out of line, out of whack. Um, so, you know, I kind of think severity, um, is a bit of a funny concept in some ways. So, you know, if, if, uh, if a person's partner leaves them, you know, in awful circumstances because they, um, you know, they cheated on them and they betrayed them and they've, you know, left their family. If that person, you know, screams or loss and cries a lot, you know, and lies in bed more than somebody else in the same circumstance, you know, we would say that's more severe depression because on the PHQ or the Hamby it's more. But. You know, sort of in some ways. Does that really help you work out what to do with that person if they've got, you know, 25 out of 25 intensity of symptoms versus 625, you know, they've both got, you know, a severe existential problem with who they are. You know, they've lost their attachments. You know, they feel betrayed. They feel the shame. They feel lost. You know, the issues are the same. If they scream louder, does that make it a different condition? So I kind of still think that understanding what are the existential circumstances that's causing somebody, you know, mood makes the most sense of it, rather than looking at, um, you know, how severe it is. Although I understand, of course, that if someone's not eating and drinking, you now have a much more immediate problem than than their existential issues because their life is being risked. And I understand that there are extra, um, uh, things that have to be done in that situation, but I, I do I do think that some people will get into very bad places, you know, exactly some sort of downward spiral that can lead you there, you know, and I guess the only I can't point to research except to say that I've been in that position, you know, and it was, it was, uh, you know, it was existential issues that got me there. So I think that it's just a property of, you know, the human mind that it can end up in such dark places, you know? And for me, the solutions were largely existential and not, you know, not biological. Although I know that that I think that I think you probably put your finger on a very important thing. You know, when you see someone in that state, you think biology because it looks very biological, you know, this looks like a, you know, an illness state. You know, I think when people talk about mild to moderate depression, there's much less of this, you know, people people say, oh, I've everyone's been in that state very, you know, commonly people can recognize that whereas this looks something different. I think there are ways to get there, you know, that don't necessarily mean there's something being broken biologically. Yeah. And I and I don't I agree with you. But what I think, I think it would be really useful to know what might happen between that moderate and that more severe stage. And I think there's this idea. It's applied to many things, not just the illness, but that things go wrong very, very slowly and then all at once. And I wonder if some sort of physiological cascade might be, uh, involved in that transition from more moderate, what we call more mild to moderate to more severe depression. That wouldn't change really anything of what we've said so far. The ultimate cause is the existential problems. And certainly in the medium to long term, those would need to be addressed. But I often find in psychiatry, the general gist of treatment guidelines is that more biological interventions tend to be more appropriate in more acute, severe situations. Do you agree with that notion? So for example, taking the idea of something like an antidepressant. Do you think that might be appropriate in a case where someone is in hospital with their low mood, bedbound and reluctant to eat or drink? Is that a situation where perhaps something like an antidepressant or ECT, as you mentioned, might be useful? You know, what I find useful actually is to talk about dogs. Sorry to suggest it. Um, I feel like there's much less, um, confusion when you talk about dogs and about people. If you went into a what is it? What is it called, a pound? That's American. I don't know, the British term is a kennel or whatever. You know, where a dogs that have been, um, you know, left by their owners have taken somewhere. If you saw a dog, you know, that had had all its fur ripped. It was bleeding. It was lying in a corner, you know, it was, I don't know, banging its head against the the kennel. It was, I don't know, self-harming, ripping itself, you know, lying down, barely eating. What would the dog needs? I think we would all say the dog needs care. You know, it's been there because it's been abused. It's been whatever thrown around. It needs care. It needs to, you know, have its fur fixed. Give them food, make sure it feels safe. And I don't know about dog prognosis, but it will probably get better over time given that sort of thing, is there a point at which that dog needs drugs or ect? You know, I just saw I just sort of saw I sort of use the same frame with people, then go and get into very, very dark places, you know. Yes. As you say, it's like mildly retarded and very negative and suicidal. But I still think, you know, I don't, I don't um, I still think the same thing applies to the, to the beaten dog. Um, for the severely depressed person, I still think the same sorts of things care and attention and trying to solve their problems is what's going to make a big difference. Um, you know, I get doctors have a lot of pressure on them. They think that, you know, if someone's life is imminently a danger, they want to do. They want to take, um, very, um, you know, um, uh, robust action. But I still have in my mind that that that beaten up dog. Um, do you think as doctors were just far too conditioned for seeing drugs and other similar biological interventions as the, as the treatments for people's problems? And we just need to get out of this operant conditioning we've become victims of. I mean, in short, yes. I mean, of course, that's that's the you know, that's the um, that's the in the basis of psychiatry that we're doctors trained in biological treatments, applying it to mental disorders. You know, and the premise behind that is that underneath all of these mental disorders will be some kind of brain or biological problem, and therefore it makes sense to use biological treatments. Um, and so, you know, when once you're a doctor, that's what you're going to do because, you know, in the team you're in, you've got social workers for social things, you've got psychologists for, uh, you know, psychological issues. And so you're left with the biological, um, treatments as being the main purview of doctors. Of course, there's some overlap with therapy, of course. But yes, you know, that's one of the issues here that that psychiatrists are, you know, embedded in a, in a basically biomedical paradigm, and therefore they apply biomedical solutions to problems, I think, which in many cases are not best understood as biomedical issues. And that is why I think that a lot of harm can be done with that kind of approach. And y can be also highly ineffective, like the case you gave, uh, with the psychotherapy patient. And, um, going back to the beginning where you highlighted this difference, this gap between clinical guidelines and research and anecdotal information from patients on forums. And I myself have often found you can get really valuable information about what the experience of a drug is like from a forum or even from YouTube, someone talking about their first hand experiences. to be valuable for me as a clinician who hasn't really tried psychiatric drugs to to. To get that kind of qualitative information, why do you think that gap exists? There's been a lot of research now on psychiatric drugs. Why is there such a profound gap? Why did, for example, why was I not taught about emotional blunting in my training? Yeah, because of money, basically. Um, you know, obviously, you know, the drug, the pharmaceutical industry is either the largest or the second largest industry on Earth, you know, between fossil fuel industry and, and the tech industry. And they produce most of the research that that exists. You know, I know antidepressants particularly well. They produce 97% of the research in that area. And they produce research that's not aimed at improving public health, but improving sales. And so often the premises of the studies that they conduct are to show their drugs in the best light. So I'll give you, you know, a very specific example of the area I've just talked about. Why do withdrawal effects appear to be mild and brief in the literature, but they're severe and long lasting in real life. That's because, um, drug companies did studies of people who had been on antidepressants for eight weeks. And if you stop the drugs after eight weeks, most people have mild and brief symptoms. Not everybody. Some people already have severe symptoms after just eight weeks. But what the drug companies do is they produce many studies like that, and they printed them out and they and they sent them round to the key opinion leaders in America and the UK and Europe. And it was repeated so much it entered the guidelines. So the Nice guidelines for many years said withdrawal effects are brief and mild. Of course, ignoring the fact that people are on these drugs for years and decades. And the longer on the drugs, the more severe the withdrawal effects are. So to me, it's a bit like a car company crashing its car into a wall at five kilometres an hour and saying it's safe, and ignoring the fact that people are driving around at 60km an hour. And in general, that's what happens. Drug companies, you know, a kind of marking their own homework. So they are conducting studies that that are set up in all sorts of different ways We can talk about that, make the drugs look more positive than they really are, and minimizes the harms then they pay. Professors of psychiatry at King's or at UCL or at Oxford, Cambridge, Harvard to give lectures about those drugs. Those professors then set the exams. They set the Royal College of Psychiatrists learning modules. And so it's been described as doctors are actually they think they're very independently minded with critical thinking, but they're actually existing within an entire stage managed, um, situation where the study is being produced. The people telling about the studies, the people setting exams are all kind of part of a system where they're all influenced by, you know, large amounts of money from, from industry. And so I think that's why it's so jarring when you go talk to actual patients about what their experience is. And of course, doctors have been taught, you know, that's anecdotal, but what's in the textbooks? That's evidence based medicine. You know, it is in a very narrow sense. You know, when you look at short term studies, they buy some studies to be positive towards the drugs. You know, it's a very it's a very misleading slice of evidence. Um, and so I guess that's, you know, that's why um, I think that's why there's such a big difference. You know, that's just giving you an example with withdrawal. That's true for the effectiveness of anti-depressants, their harms, and a whole lot about the psychiatric drug classes where that's where the evidence is often skewed by financial interests. Have you received much criticism or pushback, whether it's from pharmaceutical companies, major research institutions, prominent psychiatrists about the kinds of things that you're talking about? Um, I've received a range of feedback. So, um, since I've started publishing about how to safely stop psychiatric drugs, I've received 22,000 emails now and counting, um, mostly from patients, but also from clinicians asking me for advice on how to safely stop their drug or their sister's drug. Some of the more interesting emails I've got are I've got emails from psychiatrists asking how to stop the drugs that they're on. I've got emails from drug company executives asking me to help their sister or their wife stop drugs. They can't come off. Um, I've been connected by by researchers in the field. Um, so I think that's an interesting snippet. Then in the public domain, I've had a lot of psychiatrists say, you know, they they've they've experienced these issues through their patients or their families, and they and they want to know more about it. And then, yes, I've had some very, you know, negative, confrontational, um, interactions with often with the key opinion leaders. So these are, you know, the academic psychiatrists who are, you know, often at Ivy League or Russell Group universities, often who have close relationships with drug companies. They get paid a lot of money every year, uh, to become the spokespeople of these companies. And they've been very critical, of course, of my work. Um, you know, they they have said, you know, the evidence based literature is much more important than anecdotal literature. They tend to ignore the studies that show that issues develop over the long term. Um, and they, you know, they've often I think, yes, they've been very, very critical of the work that I've put out. Uh, to the point where some of them have, um, you know, tried to get papers that I publish retracted. Um, you know, being said, very critical things in the papers. Um, tried to get me fired from my job, so. So I've been quite, quite aggressive in defending their interests. Well, okay, so I suppose you're and you can't fill in the gaps where I make gaps. But the response to their criticisms would be something like a lot of the research showing that antidepressants are minimally risky. That research itself is biased. There's a lot of research not showing any real clear biological cause for depression. There isn't enough research looking into all these things that people are reporting anecdotally that patients are reporting anecdotally. Did I leave anything out there? I mean, it's I guess I think it's gone. It's gone. It's gone past anecdotal things. Now there's more and more research looking at that finds that withdrawal effects from these drugs are much more common, severe and long lasting than we thought. Um, I mean, yes, minimizing long term harms. But yes, your list is a pretty good start. A list of the issues that that have been overlooked by by researchers. Yes. And in just a few minutes, we have left. Perhaps you could we will direct. You will direct listeners to a place where they can learn more, but perhaps a few general tips on coming off antidepressants. What might be a few principles you might outline? Sure. So there's basically three major principles to coming off antidepressants safely. And this is true not just for antidepressants, but for any psychiatric drug. It's easier to do it slowly than quickly. So it's easier if you do if you take it over months and sometimes more than a year. Sometimes people need years rather than weeks or days. That's because it gives your brain time to readjust to the drug not being there. I use the analogy of, you know, if you're on the 10th story of a building, if you jump from the top to the bottom, it's very quick, but you're going to get very hurt coming off it. If you walk down step by step all the way to the bottom, it's going to take you a lot longer, but it's going to cause your knees a lot less pain. And the same is true for coming off psychiatric drugs. The second issue is you've got to do it at a rate that you can tolerate. Everyone's a little bit different. There's some known risk factors the long erano drug. Certain drugs have a higher risk. And other drugs higher doses have a small increase risk. But it's very hard to predict exactly how someone's going to react. And so there's a bit of trial and error. So you got to go to right that you can tolerate. An example that I give is something like altitude sickness. If you go up too quickly up a mountain, you know your body can't handle the the lower pressure and you develop altitude sickness, headache, dizziness, feeling crappy. And the best way to fix that is to go back down again, to recalibrate to that pressure, and then go up again more slowly to the to the peak so you don't get the same altitude sickness. And the same is true for coming off psychiatric drugs. Um, if you feel withdrawal effects, you should pause, go back a step, wait for it to settle down, and then go down more slowly. And that's a bit of trial and error. And the last principle, which is is easiest if I show a it, can I show a graph or is this this is for a podcast. Yeah. So I'm just going to show you these graphs. You're saying it's basically there's a the graph. It's got venlafaxine on the x axis and it's got effect on the, it's got effect on the brain on the y axis. It's actually serotonin transporter um effect. But I'm but you can think about it as effect on the brain. And this is going to explain why it's very hard to come off the last few milligrams. So this is based on neuroimaging of the effect of these drugs on the brain. And what it shows in the in the black line is the relationship is not a straight line. Doubling the dose doesn't double the effect. So going from 75mg of venlafaxine or Effexor to 150mg of vaccine barely increases the effect on the brain at all. And even a tiny dose like, uh, ten milligrams actually has about three quarters of the effect of 300mg. Even even five milligrams has half the effect of 300mg this effect. This this relationship is much steeper than you would guess. The reason why this relationship exists is because of the law of mass action. And it basically says when there's not much drug in the system, all the receptors for the drug are open for business. And so every milligram of drug has a big effect on the brain. A bit like the game of musical chairs, when there's not many people in the game at the beginning, as there's more and more drug in the system, each milligram of drug has less and less cumulative effect. And so you get this law of diminishing returns. And so if you do what most doctors recommend, which is they might say, well, the smallest capsule of venlafaxine is 37.5mg. So you should go down by go and say from 150 to 1 12.5 to 75, 57.5. The first reduction is very easy to make for most people. The next reduction can be a little bit harder. The third reduction can be a bit hard. It can be quite unpleasant for some people. But the last reduction is like. Jumping off a cliff. It's actually about 30 times harder to go down from that last capsule of venlafaxine to zero than the first reduction. And so people experience incredibly severe symptoms in this last reduction in doctors who are unaware of this relationship will conclude that they must need the drug that they relapsing. They've got very severe symptoms. What makes more sense is what I've shown in this right hand graph is to go down by even amount of effect on the brain. So I've drawn four horizontal lines that are equally split apart. And so you can see that to go down from about 150mg, you need to go down by smaller and smaller amounts down to very small final doses before stopping, like just just a milligram or two. It's kind of like climbing down. It's like walking down this path. You need to go very carefully at the end. And so I've sort of drawn here, I've turned that graph into tables. And so here's an example of coming off venlafaxine by in what you might think of that as a pharmacologically rational way of doing it. So it's easy to start reducing at the beginning. When you get down to lower doses, you need to go down to very small final doses to be full stop. And this is actually a faster taper and some people will need even slower tapers. This is actually an excerpt from the Maudsley de prescribing guidelines that we publish, that goes through every drug that's on the market for an antidepressant, benzodiazepines drug gabapentin, and shows how to reduce it safely. And so that's the final aspect is you need to go down by very small amounts. And in order to do that, you'll see that, for example, I mentioned a lot of liquids here and that it's impossible to make up these small doses using widely available tablets or capsules. And most people will need to use a liquid version of the drug or other tricks that are off label. Uh, things like, um, opening up a capsule of venlafaxine and counting the beads inside, or getting a compounding pharmacy to make up a liquid or capsules. Or sometimes you can just crush up the tablets and mix them with water to make up these small doses. And that's the way to to come off these sort of drugs safely. Excellent. So that's a really useful explanation as to why coming off can be so counterintuitive, because I have actually encountered that with patients as well. That's coming off that last bit, even when it comes to opioid replacement, um, like methadone and so on can be really, really tricky. Um, okay. Mark, thank you so much for talking to me today. There are a few other topics set up to talk to you about at some point in the future, like tools for treating depression, Neuromodulator treatments like TMS, psychosis, bipolar, perhaps topics for the future. But in the meantime, thank you very much for joining me today. Interesting talking to Alex. Thanks very much.