Dhru Purohit Show - Top Psychiatric Expert Warns: "I Couldn't Get Off My Own Antidepressant. Here’s What Every Patient Needs to Know!” with Dr. Mark Horowitz

Episode Date: June 17, 2026

This episode is brought to you by Rythm Health, Momentous, Bon Charge, and Branch Basics. Millions of people take antidepressants to manage anxiety and depression, yet many questions remain about their long-term effectiveness and what happens when people try to stop taking them. As concerns grow about withdrawal symptoms and the challenges of coming off these medications, understanding both their benefits and limitations has never been more important. Today on The Dhru Purohit Show, Dhru sits down with Dr. Mark Horowitz to explore the widespread use of antidepressants, why so many people struggle to come off them, and how withdrawal symptoms are often misunderstood. Dr. Horowitz shares his own difficult experience tapering off antidepressants and how it inspired him to research and develop safer, evidence-based approaches for reducing these medications. He also examines the research on how antidepressants were originally approved, highlighting key limitations in some studies and how those flaws may have shaped our understanding of their benefits and risks. Along the way, he explains what happens in the brain during the tapering process and the best and worst practices for supporting individuals dealing with anxiety, depression, and antidepressant discontinuation. Dr. Mark Horowitz is a Clinical Research Fellow in Psychiatry with the NHS in London, Visiting Lecturer at King’s College London, and lead author of the Maudsley Deprescribing Guidelines, the first authoritative handbook on safely stopping antidepressants and other psychiatric medications. His research has helped shape UK national guidance on tapering psychiatric drugs, and he has published in leading journals including The Lancet Psychiatry and JAMA Psychiatry. Drawing from both his clinical expertise and personal experience coming off psychiatric medications after 20 years of use, Dr. Horowitz is dedicated to helping people safely reduce or discontinue medications when appropriate. *Important: Never stop or reduce a prescribed medication without guidance from your healthcare provider. Medication changes should be made under professional supervision, as withdrawal symptoms and individual responses can vary significantly. In this episode, Dhru and Dr. Horowitz dive into: (0:00) Introduction (00:23) The Truth About Antidepressant Effectiveness (7:10) Why Getting Off Antidepressants Can Be So Difficult (16:05) Dr. Horowitz's Personal Withdrawal Story (29:14) If Not A Chemical Imbalance, Then What? (36:19) The Neurogenesis Theory Explained (46:52) Informed Consent And What Patients Aren't Told (55:35) Why Standard Tapering Often Fails (1:02:37) The Antidepressant Controversies (1:12:25) Best And Worst Practices For Recovery (1:20:15) Resources For Healing And Support (1:24:37) Final Thoughts And Advice Also mentioned in this episode: The Maudsley Deprescribing Guidelines: Antidepressants, Benzodiazepines, Gabapentinoids and Z-drugs (The Maudsley Prescribing Guidelines Series For more on Dr. Horowitz, follow him on X/Twitter, Substack,  Outro Health’s socials: Facebook, Instagram, X/Twitter, LinkedIn, YouTube, or visit his Websites: Dr. Mark Horowitz and Outro Health. This episode is brought to you by Rhythm Health, Momentous, Bon Charge, and Branch Basics. Right now, Rythm is offering my community 15% off your first month, plus free shipping at Rythm Health. Just go to rythm.health/DHRU to get 15% off at checkout. Right now, Momentous is offering our listeners up to 35% off their first order with promo code DHRU. Head to livemomentous.com and use code DHRU for 35% off your first subscription. Right now, Bon Charge is offering my community 15% off their Red Light mask. Just go to boncharge.com/dhru and use code DHRU to save 15%. Right now, Branch Basics is offering 15% off the Premium Starter Kit; just go to branchbasics.com and use the coupon code DHRU. Sign up for Dhru’s Try This Newsletter Learn more about your ad choices. Visit megaphone.fm/adchoices

Dr. Mark Horwitz, welcome to the podcast. It's a pleasure to have you here. Today, we are talking about a super important subject that impacts millions around the United States, but also the world as well. And that subject is how to safely get off of antidepressants if that's the right fit for you. So let's set the stage for the conversation today.

One in six adults is on an antidepressant. most stay on it for years, but these drugs were only ever tested for eight to 12 weeks in these early trials. So we have millions of people taking medications long term that we've never studied properly long term. That's the key, properly. And most have no idea how hard it is to get off of it or why they would want to get off of it. How did this happen that we ended up in this big mess? There's about 50 million people in America taking these drugs, one in six adults,

about one in 10 children are on these drugs as well, so it's a lot of people. And the average time people are on these drugs in America is about five years. So about 20 or 25 million people are on these drugs for more than five years. But as you say, 97% of the drugs of all studies for antidepressants go for eight to 12 weeks.

And there's a famous professor of psychiatry who describes the long-term use of antidepressants as the biggest open-air experiment ever conducted on human beings. And so we really don't know exactly what. That's Alan Francis, by the way. He was the chief architect of DSM-4, a very highly respected psychiatrist.

So we really don't know what these drugs are doing long term. How did this happen? There's a few strands to this. The FDA is the organization that approves these drugs. And to get a drug on the market, you need to show that the drug is better than placebo in two trials that go for about eight to 12 weeks. And so all of these drugs, Prozac, Zoloft, effects or Sembolta, Lovox, I've all been approved onto the market because of these short-term trials.

That can be very misleading because drugs. that are a little bit effective in the short term. That's what the trials show that they're slightly better than placebo, not very much, but a little bit better. Can wear off over time. That's tolerance. We all know that for caffeine or alcohol or benzodiazepines. The same thing's true for antidepressants.

And we also don't get a very good insight into their long-term harms. So as an example, in these short-term trials, antidepressants didn't cause much weight gain, the new antidepressants. But in long-term trials, it's very clear they're. they cause about a third of people to become overweight or obese. And of course, short-term trials are not a good way to see what happens in the long-term. If you give someone alcohol for eight weeks, you don't see significant liver disease or issues with their cognition. You need longer-term trials to see that, and they don't exist for antidepressants in a very structured way.

The other issue is that the FDA doesn't demand that manufacturers of these drugs, show that they can be stopped easily. So, for example, this will come up again in future conversations here. What the drug companies do is after eight weeks, they stop people taking antidepressants and they look at withdrawal effects, not very carefully, but they have a look.

And what they find is, most people have brief and mild symptoms when they come off antidepressants after eight weeks. And that's what's entered guidelines. If you stop antidepressants, you'll get brief and mild symptoms. Now, focusing on the 20 million people or so that are on the drugs for years, it's a very different story. Being on a drug for eight weeks versus eight years is a very different proposition.

And so we know that a lot of people on long-term antidepressants will have severe and even long-lasting withdrawal symptoms for months or years. We can talk about further. So to me, the analogy that springs to mind is it's a little bit like a car company crashing its car into a wall at five miles an hour and saying it's safe on impact and ignoring the fact that people are driving around at 60 miles an hour on the roads. How has this come about? It's because short-term trials conducted by manufacturers have kind of enter the academic literature, entered guidelines, medical education. So all doctors are taught in their training. It's very easy to come off these drugs.

Symptoms are mild and brief. And so when long-term users come off their drugs and they get hit by a lorry, severe and long-lasting withdrawal symptoms, everybody is surprised, including the doctor. And that's how we have ended up in this situation. The other, the one last piece of this puzzle is a lot of guidelines recommend long-term treatment

for people with depression or anxiety. They say, if you have one episode of depression or anxiety, stay on the drug for six to 12 months. If you have more episodes, do it for a couple of years. And if you have three or more, maybe consider it lifelong. And that's the kind of dogma within medical education. But there's a very big problem with these studies.

And that is, the way they're set up is, they get people that are already on the drug, and they randomize them to either stop the drug or stay on the drug. and then they classify any deterioration in people's mental state as a return of their underlying condition and say, well, people that stop the drug get sicker so people should stay on the drug. The problem with that is they're ignoring withdrawal effects from the drug.

They don't distinguish withdrawal effects from a return of people's condition. And so the evidence that suggests this drug's long term in people is actually very flawed because they're mixing up withdrawal effects with the return of people's condition to really underline the point. Imagine if you took people who were smokers off cigarettes and measured anxiety scores, you'd say people that stop smoking get more anxious, and so they should continue smoking to prevent anxiety. That sounds ridiculous to our ears because we all know if you stop smoking and you feel anxious,

that's a withdrawal effect, and it means you should come off it more carefully. And now cigarettes and antipresents are not the same sorts of drugs, of course. But the same principle applies that if you ignore withdrawal effects, you can come to some perverse conclusions about how effective a drug is a preventing relapse. And so to put that all together, short-term trials have misled doctors into thinking that withdrawal effects on these drugs are very mild. And so patients are blindsided when they have severe effects. And the evidence for long-term use is not very strong because of the flawed way these trials are conducted. you know, so many important themes and distinctions that are there.

And I think that anybody who's listening today that might be on these drugs or definitely, even if you're not on them, you might know somebody who is. And if you know somebody that's been on it long term, especially they've dealt with, you know, some of these side effects, you'd understand why some people have the drive to see, is there a way to get off of these drugs? Maybe there was a reason that these drugs came in. These drugs definitely work. Not for the reasons that we were told long, you know, back in the day, we'll get into that in a little bit.

But they did their job. But now the patient is so scared to get off and is getting discouragement from their doctor because of these withdrawal symptoms, which people are confused under the thinking is a return or a worsening of their underlying symptoms. It's kind of a crazy world that people have to navigate. You know, withdrawal effects are a very common effect of any medication that we take, long term that our brain adapts to. There's a principle called homeostasis. We like to stay in the middle. If it's very hot outside, we sweat. If it's very cold outside, we shiver. If we're taking a drug like an antidepressant that changes levels of neurotransmitters in our brain like serotonin

or norophenephrin, our body adapts to it to become less sensitive to those chemicals. And when we stop the drug, we get withdrawal effects. The body is kind of crying out for that drug. People, when they hear withdrawal effects, always think about addiction and addictive drugs, because that's where they were first studied. People think about heroin and alcohol. When they hear it about antidepressants, it sounds quite confronting because it sounds like, well, naughty drugs cause withdrawal, but drugs prescribed by doctors don't. But, you know, the body doesn't really distinguish between drugs that are prescribed by doctors or recreational drugs, our bodies react to any change in balance to try to restore that balance. And when the drug is removed, the balance is

disrupted. So as a sort of example, I'm sure that a lot of your audience, probably you too true, are physically dependent on caffeine. I know I am. And if you were to stop drinking caffeine, you'd get a withdrawal syndrome, not a particularly severe one, maybe a headache, maybe feeling tired. I'm also going to guess you're not abusing, you're not misusing, you're not on the street trying to get more caffeine, you're not addicted to it. And the same is true for antidepressants. You don't have to misuse or abuse or be naughty in some way. Just being exposed to these drugs month after month is enough for our bodies to adapt to them. When they disappear, we get withdrawal effects. The withdrawal effects can be very confusing. Because these drugs affect a whole variety of our organs,

they can be emotional withdrawal effects or physical withdrawal effects. And the physical ones are things like brain zaps, little shocks in people's head, sometimes I'm moving their eyes, headache, dizziness, sweating, a rapidly beating heart, trouble sleeping, nightmares, a feeling of agitation called acathisia that can be very, very distressing, sort of leads people to be pacing backwards and forwards. And it's acathisia and also the emotional symptoms, things like low mood, anxiety, panic, attacks, crying spells that can get misdiagnosed as someone's underlying condition coming back. And we know that these symptoms, low mood, anxiety, panic attacks are withdrawal effects and

not just people's condition coming back. Because in studies of people who have put on antidepressants for reasons other than mental health problems, given it for the menopause, for pain, and even in healthy volunteers, when they stop these drugs, they get all those effects. And of course, you know, that should be familiar to us. Anyone has had a hangover knows that withdrawal from a drug can cause lots of emotional problems. So it shouldn't be surprising to hear that. But this is where the sort of conundrum arises. Because guidelines for many years have said withdrawal effects are not really a big deal, they're very mild.

When someone comes off their drug and they go see their doctor, or sometimes they go to the emergency department because they're really in a bad way, and they say, I've just stopped my Zoloft. I'm having panic attacks, I can't sleep. All doctors straightaway think this must be a return of their underlying condition, anxiety or depression, they think relapse. Because that's all through the textbooks. It's all through drug company studies. And almost nobody thinks of withdrawal because that's so far down the list of priorities in doctors' minds

because of the way education is directed. And as you mentioned, just to interrupt, they've been told by the drug companies that it's not that difficult to get off these in the first place. So nobody even warned them about that. Exactly. So doctors, you know, of course doctors are very well-meaning. I'm not putting the finger at them at all. But, you know, we're all put through our educational systems. We learn what we've been taught. And the teaching is, you can see the guidelines today. Symptoms are mild and brief, easy to come off. If people have trouble, it's probably their underlying condition. There's a lot of research now that says the opposite is true. If you have trouble coming off an antidepressant, it's more likely to be withdrawal than it is to be a return of your condition. Of course, a return of your condition is possible. Of course, that happens to some people. But the numbers now, for long-term users especially,

suggest that withdrawal effects are actually more common than relapse. But we know that misdiagnosis happens all the time. I mentioned it before, misdiagnosis in studies, where they don't look for withdrawal and they call everything relapse. The same thing happens with GPs and psychiatrists. Someone comes into their office, beside themselves, crying, sobbing. They always think of relapse. and the message given to the patient then is

you shouldn't come off your antidepressant, you need to go back on it, and actually maybe you need to be on it lifelong. So people get caught in this revolving door. They come off their drug, they feel terrible, they go back on it. I think the other thing that's very tricky is our emotions feel very familiar to us.

I would say the following. If both me and you sat down and drank a liter of coffee, we'd both become anxious. If let's say I worry about it, about my hair falling out, I might become very worried about my balding. And if you worry about your family, you might worry about your family. In other words, although it's the chemical causing the anxiety, the pattern, the nature, the idiosyncrasies, the specificity of the anxieties are determined

by our patterns of thought. And so when people become depressed or anxious when they come off an antidepressant because of withdrawal effects, it can feel very familiar to how they generally feel if they feel down. You know, I sometimes say to people, you know, when you have a breakup, with a partner or a hangover, there's a little bit of similarity between feeling crappy in those situations. You know, there is kind of a generic. Yes, there's more dry mouth in hangovers and there's more anguish in heartbreak, but there is a kind of generic feeling of being down. And so patient's mistake withdrawal effects for relapse. Doctors are taught it's relapse. So there's kind of relapse first in everyone's minds because most people haven't even heard about withdrawal. And so for lots of

reasons, withdrawal is not spotted carefully. That's led to this kind of interesting phenomenon, somewhat worrying, where patients give up on their doctors. They sort of say, this is very strange. I went on this drug when my mother died and I was very upset and maybe I was glad to have the medication because it made things settle down. But now, five years after my mother died, I feel fine. I've come off and I've developed panic attacks. I can't sleep and I feel anxious all the time. But when I went on the drug, I was lethargic, I was tired, I was really low in mood. This feels totally different, but my doctor's telling me it's a relapse. And I'm thinking, how can you have a return of my mother dying? You know, that doesn't make sense to me.

And so they kind of lose faith in their doctors. And they go like everyone does, they type into Google, maybe chat GPT these days. And they find lots of other people who are having the same problems with withdrawal and they think, I'm going to seek these people's advice on social media rather than my doctor because they seem to get what's going on in a way my doctor doesn't seem to. And so we have a lot of people who are leaving mainstream medical care to go to social media sites to get advice because doctors are poorly informed. Normally, probably have a doctor saying, look, people are being mad, they're going to social media, they should be able to doctors. but it's quite the inverse in this situation where doctors are quite poorly informed,

not their faults, it's just the way the studies have been set up. And so actually people tend to get somewhat more accurate advice on Reddit threads and Facebook groups and from their doctors. It's quite a bizarre inversion of the usual kind of hierarchy of knowledge. You know, I want to personalize this because what people may not know about your journey is that before you were the researcher, you were the patient yourself, and you went through a lot of these experiences. So take me back to your own experience of trying to come off antidepressants,

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psychiatrist. I trained in Australia and I trained in London and I, you know, I was very good at exams and I was taught all the same things that my colleagues were taught that these drugs were, you know, very easy to come off, no major problems. And I wouldn't have changed my mind until I experienced it firsthand. So I was finishing off my PhD at King's College in London, which actually while I was there past Harvard as the most cited research institute for psychiatry in the world. So I was really working with the world leaders. And I was doing my PhD on how antidepressants work. You know, I was studying, I thought I'm studying my own condition, depression and the drugs that I'm taking to try to make sense of things. And towards the end of my PhD, I read an article talking about withdrawal effects

from antidepressants. And I found that quite startling because I'd never heard about it before in my medical training, in psychiatry, in my PhD. It gave me two thoughts straight away. I thought drugs that cause withdrawal also cause tolerance. The more tolerant you are to a drug, the harder it is to stop. And I thought, at that point, I'd been on lexapro or esoteropram for 13 years. I thought, how could it be doing anything if it's causing tolerance over time? You know, caffeine wears off, benzodiazepines wear off. What is this drug doing? And number two, drugs that cause withdrawal often have a lot of toxic effects. Opioids, we know are dangerous drugs, benzodiazepines, recreational street drugs.

I thought, what is this drug? What could it be doing to me? And I actually had a lot of health problems at that time. I had a lot of trouble with daytime fatigue and concentration and memory problems. And I had a vague idea, maybe that's related to the antidepressants. As it turns out, a lot of those issues were related that I hadn't quite put it together over many years of use. And so I decided that I would try to come off my antidepressant. And I thought I would do it extremely carefully, being a pretty cautious, you know, risk-averse kind of guy. And I came off over several months, much slower than the guidelines at the time recommended over a few weeks. I actually stole into my cutting-edge molecular biology lab and I took special syringes that measured out very

small doses. I got a liquid. I went really over the top to be very careful. And when I got down to a fairly low dose of my Lexer Pro, my life kind of exploded. I had trouble sleeping. And I would wake in this state of absolute terror. What I've come to realize was actually acathisia, this sort of state. Because you come from the Greek word for can't keep still. A horrible state. I felt full of terror, full of anxiety.

And it would last for several hours of the day. I got a bit of relief in the evenings. And I took up running to just outrun some of the anxiety. And I ran onto my feet bled. I was, and it went on, this sort of state of terror and anxiety went on week after week. And at some point I thought, I cannot keep living like this. It was very, the bleakest period of my life. That was nothing like the symptoms I had when I went on the drug.

You know, I am a neurotic, pessimistic stick in the mud as a person. You know, if you've seen Woody Allen films, I would fit right in there as a character. When I was 21, I was, you know, unsure about my degree. didn't know who I was, absolutely miserable, but I never had panic attacks and never had trouble sleeping. So what I had when I was 21 when I went on the drugs, it was a three out of 10 in terms of severity compared to the 10 out of 10 when I came off the drugs. And it was a shot, absolute shock to me. Eventually, I went back on the drugs because I just couldn't tolerate how sick I was. And at that point, I realized I'm now on these drugs, not because they're helpful to

but because I can't get off them. I was really trapped, actually trapped on them. And at first I thought, look, what an unlucky person I am to have this terrible reaction. But then I went online, you know, like I'm a millennial, albeit a geriatric millennial. I did what we all do. I went on to Google. And at first I found a few dozen people with very similar stories. Then I found hundreds.

And by the end, I found groups of tens of thousands of people with the same story. And I thought, this is not just me. This is a widespread phenomenon. People with panic attacks I never had before, dizziness, acathia. And they'd all gone on the drugs because of certain life problems like me. Nothing as severe as what they had in the coming off. And I came across some groups that discussed a better way to come off antidepressants. And they suggested to come off very slowly over months and years down to very small doses,

much smaller than currently available tablets using a, liquid, if possible. I wrote an academic article about this approach and it was published in a good journal in Europe called the Lancet Psychiatry and that led, that actually triggered guideline change in the UK, the United Kingdom, so that now the official guidelines recommend my technique to come off for the 60 million people in Britain, so 60 million population, not on antidepressants. And since then, And all of my work has been on what causes withdrawal, who is lucky to get it, what are ways to avoid it, what's the best way to come off these drugs. I could talk a bit more about my technique.

And I started getting contacted by a lot of patients, especially ones in America. And that's what's led to me. I set up a clinic in the UK. That's the national deprescribing clinic to help people come off antidepressants and other psychiatric drugs because there is no such service. otherwise. And I also work in America with a place called Outro Health that helps people to come off antidepressants just because I was inundated with so many requests from American patients to come off antidepressants because most doctors just are simply not trained in how to do that as part of their

regular education. No, it's a huge body of work you have and it's incredible that you've also, I get excited anytime a doctor jumps into the entrepreneurial aspect of it because the challenge here, even in America, where we tend to have the worst of things and also the best of things when it comes to many aspects, but health care, especially, I've had so many friends over the years whose family members, wife, partner, husband, or they themselves were looking for somebody. First of all, the traditional, you know, even highly esteemed psychiatrist at all the top clinics, they just weren't aware. And then the ones that were willing to go on the journey and learn with them were often these integrative psychiatrist

or these functional psychiatrists who had a traditional degree, but like yourself, had dealt with their own mental health crisis and were open-minded enough that they would say, hey, listen, I haven't done this with a ton of patients,

but I'm open and let's go on that journey together. What's the challenge with that? They're super expensive. There's not that many of them, and it was very hard to even get in the door in the first place. The fact that there was now even a clinic that people could reach out to to get help to go on this process because, yes, you can find guidance

online, but it's also the Wild Walt West. You know, you'd much rather want to work with a trained clinician to help you on that journey. So I'm so excited that you started the clinic Outro Health. We'll link to it in the show notes. People can check it out if they have themselves or a loved or a loved one want to go on this journey of getting off antidepressants in the right way. I agree with you. It shouldn't be restricted to a few doctors that have been through it themselves. I mean, in some ways, that's mad. You know, if you have to have a cancer doctor, doctor having cancer before they treat cancer well, you know, that's not a good system. So, I mean, I'm very much keen for all doctors to know how to get people off antidepressants. Every doctor

who starts these medications should know how to stop it. You know, I would say to be like having brakes on a car, you know, if there were cars that were sold that didn't come with brakes, the car regulators would be in jail in a second. But for some reason, you know, medical education allows doctors to prescribe medications that they don't know how to stop safely. So I really think there needs to be an improvement in the education of doctors. They know how to do these things. And that's a standard practice, not an exception. Well, at the moment, there aren't that many places around, as you say.

We're going to get into all that. As we continue the conversation, we're going to talk about the standard approach that's out there just to make people more familiarized, what's recommended. We're going to talk about some of your techniques and approaches that are there that you followed yourself or that your clinicians that Outra Health follow. And then we're going to go a little bit further. But before we do that, just to make. sure we touch on this because some people are aware, some people are not aware. For the longest time,

when it came to mental health, the idea with these drugs was that, hey, there's a chemical imbalance and you're going on these various drugs to address that chemical imbalance. And you yourself were part of the work suggesting that depression was never really about serotonin. That was the main chemical that was out there. So for millions of people that were told that they have a chemical imbalance and that's why they needed these pills, what does it actually mean if that story was never true? Because many people have gone on these drugs and have actually had their lives dramatically improved. I've had many friends who, you know, they themselves, even though they did a lot of things that they thought were, you know, part of healthy living, they went on these drugs

and they noticed a massive difference. So what are these drugs doing if they're not fixing a chemical imbalance? Sort of an interesting history. It's probably worth laying out just for a couple of minutes. I mean, where did this story come from? So originally in the 1960s, psychiatrists hypothesized

that depression might be caused by low serotonin and norophenephrin. And they thought that because people that were given antibiotics that increased serotonin felt happier. And they thought, well, if increasing serotonin makes people feel better. Maybe the cause of depression is low serotonin. In actual fact, that kind of thinking is very flawed. If you think about it, it's like saying, if you give someone aspirin and their headache goes away, maybe their headache is caused by a lack of aspirin. That sounds a bit silly. It's actually

got a name. It's called the ex-duvantibus fallacy, which is a fancy Latin way of saying, the opposite of the thing that fixes something isn't necessarily the cause of it. Right. But anyway, that was a hypothesis. It was a legitimate hypothesis. And there's been six decades of research since it was hypothesized in the 1960s. And to summarize our work and others, essentially there is no big difference between healthy volunteers and depressed people. If you look at serotonin in their cerebrospinal fluid, in their brains after they die, in their blood, in their urine, their serotonin genes, it essentially comes out as no difference between healthy volunteers and depressed people. And actually, you know, we were not the first to say this. Our paper got a lot of attention, but it's been known for years in academic psychiatry that depression is not caused by something as simple as low serotonin. I mean, it would be quite fantastic if, you know, a very complex emotional process that involves our relationships, our childhood, our physical health would be boiled down to a single chemical. I mean, that would be quite extraordinary. And for now many years, for example, the American Psychiatric Association

has taken off mentions of chemical imbalances and low serotonin from its websites. Prominent American psychiatrists have said, no psychiatrist worth their salt has ever really believed this. It was a bit of an urban myth. It was something that they told patients to make it seem sensible to take these medications, but it was never believed as gospel. And a lot of people said that our paper that was published now four years ago was a bit boring because it showed something that was a

already known that depression was not caused by low serotonin. So there is widespread agreement on that. You know, a lot of people have been told this story. You've got low serotonin. This drug will increase serotonin. You know, it's a very compelling kind of pitch. And of course, that's why it's become so widespread. In the 1980s and 1990s, the drug manufacturers amplified this hypothesis. There was ads on TV. There's a famous sort of Zolov blob, a very unhappy blob jumping across the screen. They zoom into its brain. It's got low serotonin. They give it Zoloft. Suddenly it's out there playing with its friends in, you know, group sports.

And so that message was really given to patients. It was also given to doctors. In textbooks, in education, they sort of put out this message. This is how the drugs are working. And so we know that about 85% of the public in America believes that depression is caused by a chemical imbalance. It was a very, very successful marketing campaign. You know, linked to high rates of prescribing of antidepressants

because of course, you know, if someone said to me, Mark, you've got low thyroid hormone, do you want thyroid hormone? Of course I'd say yes. That sounds like a very neat solution. And so a lot of people that now understand that it's not caused by low serotonin feel pretty misled that they were told to take a drug, you know, on a kind of false premise that it would fix this, you know, very simple deficit of serotonin. It does raise the question of, so what does cause depression?

I think there's a few things to say about this. Number one, depression is really common. Sometimes you hear stats like one in four, but actually, really careful studies that follow people every few years from birth until the age of 45 find that 70% of the public meets criteria for clinical depression or clinical anxiety at some point in the first 45 years of their life. In other words, most of us experience clinical anxiety or depression. I sort of think about my friends and family. Most of them had a difficult period in their lives after heartbreak, divorce, job loss, the death of a loved one. People have had low periods.

I have one friend I've got in my mind who's always cheerful, he's tall, good looking and rich, you know, and I despise him absolutely. But it's very common. It's very common. So first of all, it would be a bit strange for 70% of the public to have something wrong with their brains. And what the research shows is, there's a very clear relationship between how many stressful life events you have in a year and your chance of being depressed. So if your mother dies, if you lose your job, if you get sick, if you move across the country, if you're lonely, your chance of being depressed is extremely high. If none of those things happen is extremely low. The gradient of effect is incredibly steep.

There's a 30-fold difference between people that are highly stressed by life events and people that are highly stressed by life events and people that have. have nothing going on. I don't know how to impress on you how big an effect that is. It's stronger than the effect of smoking on lung cancer. So there's all these studies looking at different chemicals. Some of them find it's 5% or 2%. There's almost no finding. But if you look at stress, it's a huge effect. And there is some genetics in that. You know, people's personalities determine how sensitive they are to stress. You know, I sort of think, I don't know, Barack Obama is very resilient to stress and Woody Allen is very non-resilient to stress and that determines things and that's in your genetics. You can't change your genetics, but it does mean there's some biology to it.

But for the most part, it's our life circumstances, maybe especially early childhood circumstances that determine our risk of depression. So what do antidepressants doing then? If it's not about a specific chemical, if it's about the context in our lives, there are all sorts of theories about how antidepressants might work. And I did my PhD on all these theories. That was my, that was four years in a lab every weekend and every evening. Does it affect inflammation? Does it affect the growth of new brain cells? This idea of neurogenesis. Does it affect stress hormones? All these studies are fairly inconclusive. They come from either animal studies. They show very minor effects. There is no clear finding. Actually, I want to just jump on, have you heard of the neurogenesis theory? Is that something

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I talk about it now. I want to explain it for our audience, yeah. Yeah, the idea behind neurogenesis is maybe depressed people have less neurogenesis, that is less growth of new brain cells. and drugs like antidepressants and maybe psychedelics increase the growth of new brain cells. And that's what I did my PhD on. I thought it was a fascinating topic. You know, we can actually affect the way the brain, you know, functions.

The evidence is kind of mixed. But after my PhD, someone said to me, you know, lots of things that damage the brain also caused neurogenesis, the growth of new brain cells. Strokes do, blunt trauma to the head and chemical damage in the same way as if you cut your skin, you get the growth of new skin cells. So, you know, after I spent four years

killing myself on the weekends on looking at neurogenesis for antidepress, I thought, so it could mean the drugs that cause neurogenesis are actually causing damage to the brain and the new brain cells growing is a sign of repair. And I guess it comes down to the question of,

is it likely that these drug manufacturers have found miracle growth for the brain or that these drugs are a bit toxic to the brain? So every time I hear neurogenesis now, I used to think, oh, that's great. It must be good to have new brain cells. Now I'm not so certain whether that's a good or bad thing. But in any case, it hasn't been shown conclusively for antidepressants. So it does leave this question of how do these drugs work? I think the honest answer is we don't know, but

in many, many studies of patients on antidepressants, they all say the same thing when you ask them, how do they feel? And they say emotionally blunted, emotionally restricted, suppressed in their emotions. What of that means is the range of emotions from very positive excitement, joy, love, enthusiasm to very negative, panic, low mood anxiety is squished into the middle. So they don't feel the same highs, they don't feel the same lows, they feel the volume has been turned down. And you can see why if you're very panicked, very anxious, very depressed, that turning the volume down from a 10 to a 3 can be a big relief. But you can also understand why it's the number one reason people come to our clinic in America and the UK to get off antidepressants because they say,

I don't cry anymore, I don't feel enthusiastic about things in life anymore. I'm not sure what I think about my spouse, children, family, because I don't have strong emotions inside me anymore. And so I think there are consequences to numbing people's emotions in the long term that we didn't really think about in these short term studies. The emotional numbing is also connected to sexual numbing. So these drugs cause most people to have sexual reduction in desire, sensation, ability to have an erection, the ability to orgasm in both sexes. Emotional numbing and sexual numbing correlate in studies. And the other thing, because I do a lot of work on liquid versions of the drugs to get people off, if you crush up an antidepressant and swish it around your mouth, it

numbs your mouth slightly. In other words, there are mild anesthetic properties to these drugs. I think it's worth stepping back and thinking about what the implications of this is. Because a drug that fixes the chemical imbalance sounds like it's solving a core problem. You know, sounds like a very good idea. People compare that to giving insulin to diabetics. Obviously, that's a very sensible, safe, you know, wise thing to do. But if in fact what we're doing is giving drugs that numb people's emotions, which means they're sort of altering the way the brain should be working.

Because if we, you know, we get numb from alcohol, we know that that means it's causing the brain not to quite, excuse me, not to quite function in the way that it should, in actual fact, to put a really kind of blunt point on it, the drugs themselves are causing a chemical imbalance because if there's not an abnormality of serotonin, by taking these drugs that increase serotonin, we are changing the chemistry of the brain. And I think that makes, that makes, should make us think what are the long-term consequences of using drugs like that? I think there is a much stronger argument for short-term use of numbing of things that give you a bit of a break. But in the long term, what are the biological consequences of change in the chemistry of the brain?

And there are some signs that some worrying things happen. People develop long-lasting sexual problems that don't go away when they stop the drugs. People develop these long-lasting withdrawal syndromes. People can develop all sorts of side effects, muscle twitching, trouble with sleep, increase in anxiety. weight gain, memory problems, concentration issues. So there are significant consequences to long-term use of these drugs that I think is concealed by that very neat story of them fixing serotonin. So I think we should be really thinking about what is the best way to use these drugs. And I think the answer is much more short term because of the fact that it's really making things a little bit

abnormal in terms of the chemical balance of the brain. No, such an important framework. And thank you for that. You know, it's obviously very clear that some people have gone on these drugs and they felt like it's been a major difference for them. And then it's obviously very clear that there's a lot of people that stay on these drugs and feel completely numb and feel trapped because of all the side effects that come along with being on these drugs long term. And then you add in this other layer, which is as the world of medicine continues to evolve and some of the research becomes more well-known, people also realize that there are major lifestyle components to the idea of depression, your physical activity,

and how important that is. So some of my friends have done the best on these drugs who have had to go on them, not like I have a ton, but I have a few, have used it short term, maybe during a very traumatic period of their life and working with their doctor to be on it. And then have been able to get off of it early enough and supplement it with other areas, you know, all individual people figure that out on their own, right? Everybody has their own journey on that. Maybe for somebody it was cleaning up their diet and getting off of ultra-processed foods and lowering the level of inflammation in their body and increasing their level of fish oil and other things that are not a fix on it, but are contributors to our core state of inflammation and maybe ways that we

don't even fully understand play into the idea of making our depressive episodes worse when we're on them. So I think that, you know, getting on to get off sounds like the best use of these things if it's the right fit for an individual. But that's the biggest problem is that if people so choose to want to explore to get off, there's not the proper guidance and approach that's there. I do want to say that, you know, some people say, well, I sound very. negative out the drugs and I'm shaming people for being on the pills. Of course I'm not. I took them for 21 years so I'm not in a position to tell anyone they shouldn't be using these drugs. I do think you're making important points. I do think people should be, I think it's all about informed consent.

You know, I think people should know how the drugs are working, how effective they are, what alternatives are, what the side effects are, how long is an appropriate period to use them for, then they can make more informed choices. I do think you're touching on some important points. I think short term, you know, as a band-aid, makes more sense than long-term use. I do think people benefit from them. Like you said, you've got friends like that. I've got friends like that. I do think they do wear off over time and so that short-term use makes more sense.

I do think that kind of the calculus can change after a couple of years when the issue is passed. I also worry that people, maybe their attention is moved from the core issues. You're talking about all the physical issues, and I agree with that. diet, exercise, you know, how we're living people, people, if they're overweight, if they're not, yes, their diet's not healthy, their exercise isn't, isn't right. That's a part of things. People's life circumstances, their relationships, their jobs. Of course, it's not easy, you know, it's not very easy to wave a magic wand and fix your job and fix your relationship, but I think it's good to understand that it is our social context that plays a big role

in how we feel. You know, in some ways our mood is a bit of a readout for how well our life is going. And I think that medicalizing these issues is dangerous for some people because you turn social problems, financial problems, relationship discord into a medical problem. And then, you know, you're seeing a guy with the white coat, giving out medications, you can have side effects. That can lead to years of changing drugs and side effects. And all the time you're sort of drawing attention away from the core social issues. So I do, I am afraid that especially in America, there has been over-medicalization of people's moods. I'm not saying some people don't benefit from from, from, from, from drugs, but I think getting down to the core drivers of our mood, which are our circumstances,

you know, is a risk that is lost in the kind of medication boom. You know, you mentioned exercise and diet and so forth. You know, in the UK, we have government guidelines from the equivalent of the CDC. It's called Nice in the UK. And they say that there are 19 equally effective treatments for depression, equally cost effective as well in the short term. Three of them involve antidepressants and the other ones involved problem solving therapy, exercise, mindfulness, various forms of therapy, and some of those are actually more effective in the long term than medication. So when people say, you know, medication is the only option, that's no longer true. There's lots of evidence, lots of other things, some of which you've mentioned are effective.

And so we really need to broaden the options that people have available to them and not be so medication-centric as we have been for so long, especially in America. I'm so glad he said that because I'm 100% on board on that. And it reminds me of a story of an integrated physician who's been on this and psychiatrist has been on this podcast shared. If I could just share this story, it's a very short one. Is a dear friend of mine, Dr. Omed Naim, very sweet guy, has helped a lot of people in my network through his integrative psychiatry approach.

He was sharing a story of early in his career in psychiatry. He was a resident in the psychiatric department, and he remembers being witness to this very telling story that highlights exactly what you're saying. A woman came in and she was expressing the fact that she felt really down and really depressed and that she wasn't feeling good and that, you know, her friends tried to help her out, but ultimately she thought, let me go see a doctor and see if there's anything that I can do about it. And the psychiatrist who was working with her, you know, was asking some questions, going through stuff. And then ultimately, you know, he was saying, like, is there anything

recently that ended up happening, you know, to you, life circumstances? And what she had shared is that she recently found out that her longtime partner had cheated on her. And the person that she had that they had cheated on with that that person had tested positive for HIV. And now she was in this boat, don't remember exactly the specifics, where she was also trying to figure out, did she have exposure to this situation? And he was thinking even early on in his career of like, and this woman ultimately ended up being given, I believe, in SSRI, if I remember the story correctly. It's like, is this person depressed or are they going?

going through a really f*** up situation that any one of us in that same exact situation would be experiencing these same emotions and feelings and anguish and hurt and heartbreak and anger. So are you depressed with the serotonin deficiency or are you going through something really messed up as a human being and you need a lot of support and a lot of love in this process? And should we be medicalized? this situation, or should we be treating it from a human level of, wow, I can imagine going through this is the most toughest thing anybody's going through. Let's get you all the support and help that's out there that doesn't come with all these downstream side effects that may not

even get to the root of why you're feeling this way in the first place. Exactly. I guess the thing to add to that is, you know, that is not an exception. That's the rule. You know, everybody that is on these drugs, it always comes down to something that happened to them. You know, you've talked about betrayal, relationship breakdown, death of a loved one. And that's what we all go through. That's by 70% of us become depressed, you know, by middle age, because it's so common. You don't need an abnormal brain to be depressed. You just need a perfectly normal human brain and for life to happen to you. We also know that most people recover with no treatment. In the old days, before medications existed, people would have breakups and divorce. And in a few months or a year,

the research shows that even very severe depression, if untreated, goes away 85% of the time in a year. And then, you know, what is the benefit of giving people like the woman you've mentioned? She's obviously in a very tough position. Now she's on a drug that might make her foggy, asleep worse, wake up tired, you know, she might have cognitive problems, sexual problems. She might be a motivator. They talk about the amotivational antidepressant syndrome. Might that affect her finding a new partner or dealing with the court case, whatever it is that comes out. So I do think that our, you know, the medicalization of our normal moods, you know, because of drug company advertising, because of the way the medical system is set up,

has really made us jump to medical solutions that probably don't make a lot of sense for majority of people with, as you say, very understandable anxiety and depression. That's a normal response to life. It's an indication of what's going on that requires support and understanding people around us, whether it's family, friends or therapists. I do think we have gone very, very far down the medicalization route in America. And that's why there's tens and millions of people on these drugs. And as part of that, we've also in America, we have a big, we've gone through a history

where a lot of people who are seeking help for mental health were stigmatized. You know, not that this is unique to America. I have a lot of friends in the UK. This, you know, goes on in other countries as well. And so part of that that's there is that people, even me, are trying to be very cautious to make sure that we don't over-stigmatize. And it's good. It's good to be cautious.

It's good to be, you know, it's good to be aware of the different things that people are going to. We don't want to add to the stigma, but we don't want that to prevent us from talking about the situation honestly. And that's what we're doing today by having you on the podcast. You're talking about the pros, the cons, and you're leaning into informed consent for everybody who's listening. Of course I'm for de-stigmatizing, talking about mental health. I mean, you know, I'm here because I was depressed as a young person. I took medications. you know, of course I'm not, I'm not shame anybody for using medication or for being depressed.

I guess what I'm trying to get across is destigmatizing doesn't mean medicalizing. You know, being able to talk about things with friends and family, being open out. That's all very important, you know, and I'm very encouraging of that. But, you know, there was a lot of marketing that if you have these sort of problems, you should go see your doctor, you know, and that could be responsible in some cases, but I think in a lot of cases it can lead to over-medicalization. So, of course, you know, I want people to feel comfortable to talk about these things, but all them to be informed about the different choices out there absolutely when they're making a choice for themselves.

So let's talk about the standard approach when it comes to getting off of antidepressants. And I think that the standard approach is basically you half your dose and then half it again. And you argue that that approach is what sets people up to crash. So what else do you want to add to the standard approach? And can you contrast that with some of the core teachings that, that you guys bring in with your group, especially Outra Health, or what you train clinicians on as well. You're exactly right.

You know, the most common approach is you come in, and let's say you're on 20 milligrams of Selexor, it's a very common dose in America. The doctor might say, let's get you off in about four weeks. We'll get you down to half of a tablet for two weeks, then take it half a tablet every second day for two weeks and then stop it. And that sounds kind of sensible and slow, sort of even. You go 20, 10, 50,

A lot of people, we know from trials, cannot get off the drugs that way, get terrible withdrawal effects, and I'll try and explain why and then show you the approach that we take. And this is where I'm going to try and seamlessly integrate a few slides. So what I'm showing you here is nuclear imaging of people's brains that are taking antidepressants. And the example that I'm using is Sotelopram or Silexa, a very common antidepressant in America. and on the x-axis you've got dose, and on the y-axis, you've got effect on the brain. It happens to be a bit technical about serotonin,

but just think about it as effect on the brain. And the main point is it's not a straight line. So doubling the dose from 20 milligrams to 40 milligrams doesn't double the effect on the brain. In fact, it's only a small increase in effect. The smallest tablet of this drug in America is 10 milligrams, and even a little tiny dose, say 2 milligrams, which doctors would think of as kind of homeopathic or laughably small

actually has about half the effect of 60 milligrams. So what you've got is this curve here. It's sort of like the left-hand side of the arch of a door. And the reason for this curve relationship is something called the Law of Mass Action. And what it means in simple terms is, when there isn't much drug in the brain, all the receptors for that drug are open for business. the drug can easily attach to those receptors.

And so every milligram of drug at low doses has a large effect. A bit like in the game of musical chairs, it's easy to find a chair at the beginning of the game, and so this graph rises very steeply. As there's more and more drug in the system, there's less and less receptors available, less and less chairs, and so every milligram of drug has less and less effect, and you get this law of diminishing returns.

And this shape is called a hyperbola, if you remember high school maths. and that allows us to understand what happens when most doctors reduce doses of drug. So I've shown 20 milligrams 10, 5, 0, like most doctors would recommend. Going from 20 to 10 causes a reduction in effect on the brain that's reasonably small. Some people find that to be quite unpleasant. Some people can tolerate it. Going from 10 to 5 is a bigger jump again.

It can make people feel even worse. But going from five milligrams to zero milligrams is like jumping off a cliff. It's a very steep part of the curve and people basically crash at that point. This is exactly what patients describe that coming off the first few milligrams is fairly easy and the last few milligrams are hell. And in fact, that last drop from five milligrams to zero causes 20 times the effect of going from 20 to 15. When doctors are not aware of this relationship, they can conclude the person must need

the drug, they must have got depressed again, they need to be back on this drug maybe lifelong. What makes more sense to coming off these drugs is not to reduce by even amounts of dose on the x-axis, but to reduce by even amounts of effect on the brain. So in this diagram, I've drawn four horizontal lines separated by 20 percentage points, and that corresponds to smaller and smaller-sized reductions in dose. down to these very small final doses. So when you go down from this tiny dose to nothing, it doesn't cause a bigger change in effect on the brain

than the previous reductions. You could think about this as walking down this graph. It starts off as a very flat graph. You can walk like on a country stroll. It becomes steeper and steeper. And as it turns into a cliff, you have to go down by smaller and smaller steps like climbing down a cliff.

And because this graph is a hyperbola, this pattern of tapering, getting smaller and smaller as you get down to lower doses, is called hyperbolic tapering. And the key issue is because the smallest tablet in America is 10 milligrams, you need to use a different technique to make those small doses to make it easy to come off, to sort of ease the landing. You need to use liquids. You might need to go to a specialist compounding pharmacy to make up a small capsule.

There are ways to do it. It can be more expensive. but what we know from studies now is people are much more likely to get off their drugs, not end up in withdrawal, not have these terrible problems, if they do it in this slower way than in the faster way than most doctors currently recommend.

That's great. I love the visual because it really drives the idea home that it's that tiny little tweak of these, I don't know if the right term is fractional dosing or whatever it might be, that makes all the difference in terms of the letdown of getting people off of this process and allowing their body to achieve that homeostasis in a much more peaceful and stabilized way. And that is the difference between somebody who can get off of this generally through a very smooth process

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I sort of compare it to, there's two ways to get down from a tall building. In the kind of standard way the doctors recommend, it's like jumping out of the seventh-story window to the pavement with predictably bad consequences. The way that I'm suggesting is to walk down the stairwell in the middle of the building. And that's, of course, it takes longer. You've got to go by smaller steps, but it does make a huge difference to how you land at the bottom. And so I think that's a, it's very, it's very unfortunate in my view that most doctors don't understand this relationship. But it is, you know, I get gasps when I lecture all the time to GPs and psychiatrists.

When I pull up that picture, they gasp because they realize what they've been doing. And I hope more people are aware of these issues with time. So this world is pretty controversial in your community, right? There's a lot of different views that people have, people not up to date on the latest information. and you have leaned into that controversy and addressed it head on. But give a little bit of a snapshot. Because, you know, folks that are listening here,

everything you're saying, they're nodding their head, they're, oh my gosh, this is amazing. This makes so much sense. If this makes so much sense and it's so obvious, like, why isn't everybody doing this? And part of that is that layer of some of that controversy. So explain the landscape. Who are the detractors, the people that feel that,

that this isn't needed, it isn't useful, there's not enough research on it, who are the groups and what do they believe? Yeah, okay, fair question. It's interesting, I lecture to lots of different audiences. I lecture to the public. And when I lecture to the public, I just get lots of nodding heads,

people come up to me afterwards and ask, when I come up my drug, exactly like you said, it was withdrawal, how to, which liquid do I use? I get inundated with questions. When I go to talk to kind of suburban GPs and suburban psychiatrists, I get the same sorts of questions. Which drug should I use? Which is the right way? You know, this is very useful. The pushback comes from the academic class of psychiatrists. These are those sort of professors, you know,

different Ivy League universities or the equivalent around the world. Most of these professors have worked with drug companies. You can look at their academic papers and you can see a long list of conflicts of interest. They've been paid by Eli Lilly, AstraZeneca, Pfizer, all the big companies. And many of them have spent years delivering this message to the public. You know, you probably know the Purdue farmer opioid story. You know, how did they become so successful? It was because they had professors at Stanford and Harvard and so forth saying to other doctors, these drugs are not addictive. If someone has pain, you know, you need to increase the dose. Of course, that's sort of, you know, that was obviously a major scandal. But that issue,

Of course, antipers are not as dangerous as opioids. You know, opioid stop you breathing. It's not the same level of risk. But the same patterns exist in the promotion of these drugs. So very famous professors have told the public, depression is caused by low serotonin. These drugs are very easy to stop. They're very symptoms. Withdrawal symptoms are brief and mild.

And so a lot of very senior doctors are a little bit embarrassed by what's happening. You know, if you go on social media now, there are thousands of people on Twitter, on Facebook, complaining about withdrawal effects and that they were misled by their doctors. So there's a bit of pushback to try to say, look, these are patients, they're crazy, you can't take what they're saying seriously, they always complain, you know, I don't know what's going on with them, but it's not the drugs. And what they do to sort of make their arguments more compelling is they conduct meta-analyses of these studies.

So I think you maybe have come across a famous one in JAMA psychiatry last year. with first author CalFAS. And they said, withdrawal effects are not a very big deal, maybe a slight increase. You know, it shouldn't be a major problem. If you look at that study, there's two important things about it.

Number one, the length of time that people are on the drugs in that study is eight to 12 weeks. So what they've actually done is they've gone back to those studies from the 1990s that went for a few weeks done by drug manufacturers. They've put them together.

They've done sort of the latest techniques in checking, of bias and, you know, they make it look very advanced. But there's a saying, you know, garbage in, garbage out. If you put in eight-week studies, you're going to find mild and brief symptoms. So I think what they've done is correct, and it's very accurate for short-term users. If you've only been on anti-presence for eight to 12 weeks, I agree with CalFAS and so forth, you will not have major trouble stopping. Absolutely true. But for the 20, 25 million Americans who are on the drugs for two or three years or five years or 10 years, it's a very different story. And so it's a very misleading study

because they're very keen to kind of defend their names. And they came out and they said, this applies to all patients. That's the bit that I disagree with. They said, this shows that withdrawal is not a major issue for people taking antidepressants. And we shouldn't tell patients about withdrawal effects. They wanted to update guidelines to remove talk about withdrawal effects. I think that's a very unhelpful intervention. And I think if you look at longer term studies, which are There are quite a few of them showing quite clear effects of withdrawal. And so I think by looking at the wrong side of the graph, and the second point about that,

I've already mentioned, is most of the authors of that paper worked with drug companies. Some of them have been paid millions of dollars. They were the spokespeople. I sort of say in the same way that Beyonce or Kim Kardashian is the spokesperson for Maybeleen or Makeup Brands. Often it's these professors that become the spokesmen. for psychiatric drug manufacturers.

And they're often being paid more by drug manufacturers than by their university. So I think of them as spokespeople first, academic second. And I think it's very unfortunate that they've muddied the water. So I think they have, in my view, they've stirred up a controversy that's not really there. I think it is clear, short-term users, not major problems, long-term users much more likely to have problems. That has made it harder to, I think, progress on this issue because you know, what people like me are advocating for is to take people off these drugs more carefully and more slowly. It's not a very radical move. You know, I'm not saying, you know, it's actually

conservative. I'm saying come off more slowly, get down to lower doses. And they have, they find that very, I think, personally confronting because it means that what they've been saying to the public for the last two decades has not been accurate. And I think that's why they push back so strongly, you know, very unfortunately, in my view. Yeah. And there. And Therefore, by also acknowledging that, that some people might need to come off, that most people would benefit from getting off slowly and that their withdrawal symptoms are an issue. I guess that opening up that can of worms also just opens up the whole can of worms of RSSRIs, the first line therapy approach that should be prescribed in many of these situations. Or should we take a little bit more of an approach to look at many other proofs that? things that are there, or at least have the patient have more informed consent.

I guess if you're opening the can of worms on withdrawal symptoms, that also, I can imagine, is very scary for these drug companies and the spokespeople that are part of it, that, okay, what's next after that? Are we going to question the role and place of SSRIs within the context where clearly they've worked so hard to establish them as the hierarchy of approaches? is. Withdrawal is a bit a thread that starts to unravel the jumper a little bit. And I'll just make the point again at the risk of being slightly boring.

Withdrawal is not just about how hard is to come off the drugs. It also undermines the evidence for long-term use, like I mentioned at the beginning of our conversation. Because the guidelines recommend long-term use based on studies where they stop the drugs very quickly and show that people feel worse, they get more anxious, they're more depressed, and they get ignore withdrawal effects. If you start to work out that those studies are not very good because withdrawal effects are mistaken for relapse and actually what we need to have and what I'm trying to do is to have studies where they compare very gradual reductions of dose staying on the drugs, which already start to show that it's a lot safer for people and therefore

it's more of them can come off. It does start to undermine the evidence for the long-term use of these drugs and exactly as you're saying it starts to bring into question, is this the best route for people. If you put it all together, you know, the drugs are based on, on randomized controlled trials, minimally effective. You know, an antidepressant beats placebo by two points on a 52 point scale. It's a very small effect. There's all sorts of reasons why that's probably exaggerated. No one could argue that these drugs are highly effective. That's even the biggest proponent, you know, can't say that. There's small effects. There's a whole host of effects, side effects I've mentioned, fatigue, insomnia, sexual side effects, memory problems,

older people, there's a risk of falls, fractures, bleeding. People on the drugs maybe even die a little bit earlier than people not on the drugs. There's a whole host of issues. I've mentioned that there's a whole set of things that are equally effective that don't involve the side effects of the drugs. There's a thing that we use in medicine, Bran, B-R-A-N, the benefits, the risks, the alternatives, and N for doing nothing. It sounds a little bit callous, but doing nothing in depression, wait and see is highly effective because after we break up with our partners, six weeks later, a lot of us are feeling a little bit better. Six months later, most of us are feeling better. So there are internal documents

from the drug companies saying, we have a bit of a problem here because natural recovery and depression is so good, there may not be space for our drugs when their drugs first got knocked back. And so even drug companies recognize that there are, you know, that depression anxiety, it's a part of life. It's not very pleasant. I've had it. I'm sure most of your audience has had it. But we don't need to use strong chemicals necessarily. And I think all these ideas about the risks of long term you start to, you know, start to raise uncomfortable questions, as you say. For somebody who's listening today and is wondering, what should I do or what is the possible roadmap for my family member, my son, daughter, etc.

And they're thinking like, you know, they've been on it for a while, right? That'll vary for different people. But then the side effects that they're dealing with is just risk reward. It's not feeling like it's worth it for them. What's the worst thing that they could do? And then what's the best thing they could do? What's the worst thing they could do that you want to put out there to people to be aware of? And then what are other alternatives and actions and steps they could take that would be in a much better direction?

Obviously, the worst possible thing to do is to just stop your drug in one day abruptly. That's, you know, public health message, you know, do not stop an antidepressant or any psychiatric drug, you know, in one day abruptly. It's a very dangerous way to do things. It's like jumping, you know, out of the seventh floor window of a building. You're very like to get withdrawal effects. It can be very, you know, cause lots of upheaval. People can have, you know, months or. years of disruption, people think, oh, withdrawals just a couple of weeks of feeling a bit,

a bit, headachey and dizzy. You know, it can be really long-lasting, very disruptive people's lives. So do not come off your drugs quickly. What's the best approach, you know, is to think it through carefully. You've got two decisions. One, should I come off and then how do I do it? The first one is you've got a way up, exactly like Drew pointed out, what are the benefits and what are the harms? You know, it's worth probably talking that through for a couple of minutes. You know, the drugs do have small beneficial effects in studies. Two points on a 52 point scale. Maybe some people have a bit more, some have a bit less.

There are also, there's also evidence that those effects are a bit exaggerated by the way the studies are done. And so probably for a lot of people, these drugs were never effective. They use an NNT, number needed to treat to get one person affected by the drug. And for antidepressants, it's 7 to 12. That means that 6 to 11 people that are given an antidepressant out of 12 don't get a positive effect. So it's very common. I mean, people all the time that say, I took this drug.

I don't think it really helped things, but I stayed on it because I thought it was the right thing to do. And so there are people that are walking around for 20 years. They're not even sure if the drug is doing anything. They're on it because they're good patients. The doctor says it's the right thing to take. They should think about, you know, is it worth it? For some people that it is effective for, it can wear off over time.

You know, we all know about tolerance. The first day you have a cup of coffee as a teenager, you're on the roof screaming. Ten years later, it has half or a quarter the effect. The same thing is true for antidepressants. So tolerance means these things can wear off. For a lot of people, you know, the divorce is 10 years ago. The post-partum depression, the child is now at university. You know, they've moved on to a new partner, a new job.

And so the stressor is no longer in their life. Is it worth being on the drug? That's the sort of benefit side. And the harm side is all those things I've mentioned. Maybe a bit of emotional numbing was useful 10 years ago. Maybe that did get them through a tough time. But now, you know, I've had people say, I don't know what I think about my spouse.

I used to love music. Now I feel cold about it. You know, I've heard the most, actually the most upsetting thing I've heard from someone as saying, I was on antidepressants during my child's upbringing and I don't think I bonded with my child properly. I don't think I was fully present. It's a very sad thing to hear.

So that's a big deal as emotional numbing. People say my sex life has gone off. It used to have a, you know, it might be age, but I also think that since I've taken this drug, I really don't get, you know, the same enjoyment out of sex. It's affected my relationship. I've got word finding difficulties. I can't remember things I had this terribly on the drug.

You know, it's shown to affect concentration and memory when people are taking these drugs even in healthy volunteers. People have weight gain, people have nausea, people have daytime tiredness. For older people, there are all sorts of risks, increased risk of bleeding, because serotonin affects the way that platelets stick together. It causes people to risk bigger bleeding problems, makes them dizzy as they can fall over and sustain fractures. There's all sorts of issues to do with long-term use as older.

adults. There are alternatives that I've mentioned. If people want, if people still have issues, there are other ways to manage things. A lot of people over time have done some of the things that you've mentioned. They've cleaned up their diet. They've looked into exercise. They've gone to therapy. So there are ways to manage things. And I guess it's worth sitting down and thinking, is this overall worth or not? And any other group I should mention is young women who might become pregnant. You know, there are clear risks of being on an antidepressant during pregnancy. There There's an increase small but significant of heart abnormalities. There's an increased risk of bleeding on delivery of low birth weight.

There's an increased risk of autistic behavior in the children, in the offspring of women on antidepressants. There's evidence showing the parts of their brain on MRIs don't develop in the same way as people who are whose mothers are not on antidepressants. So there are good reasons for women in their 20s and 30s to think about this earlier rather than later. One of the most upsetting things I have is a 39-old woman saying, I want to get pregnant tomorrow, can I get off my drugs this week? And of course, they're in a very difficult position because they've got withdrawal effects now to contend with versus the risk of being on the drugs. So the sooner people think about these things, the more they plan it, the safer

the exit they can plan. So people, that's the first step. People have to think about, is it worth it the harms versus the benefits? And then it's more simple the second question, how to come off. The answer is slower is better. You know, there are some people who can come off in four weeks. I occasionally get an email from someone who says, okay, in four weeks I had no trouble. I know that they exist. It's very hard to guess who is who.

And so to me, it's like taking a bit of a risk. You're jumping out the window of the seventh floor building. You might bounce. You might be one of those lucky people. Maybe one in four, maybe even one in two people. To me, it's better to find a doctor who knows how to oversee a slow reduction, make a small test reduction, see how you respond, maybe reduced by, say, 10% of your dose.

If it goes fine, you can go a little bit quicker. If it's difficult, go slowly. And overall, the principles that make the most sense is gradual, using a liquid or some other compounded version of the drug, adjust the rate to what you can tolerate. Everyone's a bit different and be more careful at the end. So that hyperbolic taper makes sense. Some people say, oh, are you saying that everyone should take three,

years to come off their drugs and I'm not. What I'm saying is better to be careful, a bit like driving. If you start driving too slowly, you can always speed up, no problem. But if you drive too fast and you crash, you can't just press the break. And so I'd say it's better to start off more conservatively and adjust things based on how it goes rather than going too fast. And what I found in seeing a lot of patients over the last few years is if you go at a rate that you can tolerate, Sometimes it takes 12 months, 18 months, two years, but almost everybody gets off their drug that way. Whereas the four-week way of doing it, less than half people can get off. So it really increases your chance.

And it also makes your life much less disrupted because you don't want to be white knuckling, turning up to work, having panic attacks. That's not a good way to live. And so my advice is to go carefully with a doctor that's knowledge about this way of doing things. That's fantastic. Thank you for that breakdown. That's really, really great. And for people who are looking for support on that, you mentioned, especially for the American audience that's there, there's outro, which is the company that you co-founded. How does it work just like big picture? I love having solutions for people.

And just to be clear for everybody who's listening, you know, I have no affiliation with you guys. This isn't a sponsored episode. I just want solutions for people and education. and so I'm excited for anybody that's bringing that to the table. So how does it work for somebody who's thinking about getting that assistance through a company like yours? So OutroHealth is a telehealth clinic. It's available today in 14 states in America, York, California,

and a whole bunch of other states on our website. It works. We have psychiatric nurse practitioners that are very specialized in this area. So they do a lot of training in deep prescribing in my techniques. They're supervised by psychiatrists. specialise in this area. You'd come in for a first assessment to find out about while you put on an antidepressant, what's been your experience, have you tried to come off, what's happened in the past, really get to know people. And if people are appropriate, if they could benefit from outro,

we'll get them a bespoke reduction regime, you know, very similar to what I've outlined here. It's slow. It's adjustment to the person. You know, we sort of have a kind of philosophy you should go as fast as you can, but as slowly as you need. No one is rushed, but we want to reduce people's side effects. That's often why they come to see us because of their side effects. They see a nurse practitioner every month. They can message in between. I think one of the key things that we have is monitoring.

A lot of doctors say, go down these doses, call me in six months, tell me how it's gone. We kind of allow people to check in. If things go wrong, we adjust things. And I think that really makes it much safer. We've got peer support groups because coming off your drugs is a bit of an emotional journey. It's a bit of a physical journey. I think it's good to have people around. They're going through similar things.

We're very good at knowing which drugs come as liquids, which ones need to be compounded. Do you take this twice a day? Mostly who we see are people that are long-term antidepressant users. So normally a kind of average patient is someone who's been on the drugs for five years or more, Lexopro, Prozac, Effects, or they've tried to take. come off before and got into trouble. You know, one day I hope we find people that haven't got into trouble yet. So we prevent them getting into trouble.

But often it's people that have had their fingers burnt before and know that they can't come off in the usual way. And the average time it takes to come off in outro is often more than 12 months. So much slower than kind of with doctors. And we have we have very high levels of satisfaction. It's very nice to see. I'm sort of very gratified to see my technique kind of being applied to hundreds of people and it working out.

So it's been enjoyable. We have little celebrations where people come off their drugs. And we also direct people to other ways of managing their mental health. We have a whole suite of non-drug treatments that we offer guidance on. And I think that's also very important to replace a drug with something else, something more sustainable with less side effects. And that's kind of how outro functions. That's great.

And is that also include like, you know, the person who's listening right now who is like, I don't want to go on these drugs to begin with, but. whether it's family or their partner or their doctor, sort of putting them in that direction, still attached a little bit to this idea of there's a chemical imbalance and this is just the thing that you need to fix it. Do you guys have resources for that or are any resources you want to give now

for people who haven't started but are feeling like, I don't know, should I start, but I'm not as educated about the alternatives that are out there and the different solutions. Where would you send them? Great, great idea, Drew. That's a good point. We have an outro library, which you can go for free, and it's got education about depression, antidepressants, withdrawal effects.

You could read it if you weren't on the drugs, if you are on the drugs. I have a lot of videos on YouTube under Mark Horowitz. I've got a Twitter account at Mark Horro. I've got a website. Those are probably places to look. There's a good book called Chemically Embalanced by Joanna Moncrief, one of the professors I work with that's very good on this topic. I think those would be the places to start for people who want to educate themselves about this topic.

Amazing. Well, we'll link to all those in the show notes below. Mark, as we're winding down here, any final words you want to leave our audience with? Some of your critics have said that you're a man on a ideological crusade, and all I hear from you today from having a chance to meet you for the first time

but following your work over the last few years is that you were a doctor who got him. to this field because you cared about people and you yourself were let down by the system, not because of any one person, but because of the way that the nature of the system was designed. It was an unintended consequence about how the system was set up. And yeah, if you're on a crusade, you're on the crusade of getting people healthy. So that's the only thing that I've seen that's there.

What do you want to leave our audience with? Maybe I am on a crusade. I guess the crusade is, I wish as a 20, year old when I was a very distressed, very lost, miserable young man, I wish that I had then been given the information I'm trying to get out now. I don't think I made, I don't think I gave informed consent for the drug. I didn't know that the drugs weren't that effective, that they weren't ever intended to be on for years, that when I tried to come off them, you know, I would almost die from the symptoms that I got, that that would disrupt my life for years. So I, you know,

I do get shouted out a lot by professors of psychiatry. They say that I'm a very naughty boy, but I keep in mind the young man that I was, and of course the young people around the world that are getting giving these medications, and I'm not trying to take anyone's medication away. I just hope that people understand the benefits, the risks, the alternatives, what doing nothing looks like. And for people who choose to be on medications, that they're reviewed regularly, they're not put on open-ended medications like I was,

that they're stopped appropriately after six months or 12 months, and when they're stopped, it's done safely so that they're weaned off in a gradual way rather than being thrown off. So I'm trying to minimize harm. I think that there has been too much medicalization of our moods. I was an unhappy young man

because I didn't like my course. I didn't fit in at school in many ways. These are generic problems that thousands of movies and books have been written about. It's just a part of life. I grew out of it as I got older and I matured. And so I'm very worried about a lot of people with normal life problems, being medicalized, put on medications that they can't stop very easily,

and developing a whole host of health problems. So I want to put more options on the table, give safer options, and make sure people have informed consent. If that's a crusade, then I think that's what I'm doing. Well said. Dr. Mark Horwitz, thank you for joining on the podcast and sharing your body of knowledge on an incredible topic. And I really do see that a corner is being turned. A new vision is happening through the spread of, you know, social media gets a lot of flack, but really through the power of social media, podcast and other things, there's a whole new approach that's coming to psychiatric health, and you and your team are a huge part of it. So thank you so much. Thanks, Drew, thanks for talking to you.

Hi, everyone, Drew here. Two quick things. Number one, thank you so much for listening to this podcast. If you haven't already, subscribe, just hit the subscribe button on your favorite podcast app. And by the way, if you love this episode, it would mean the world to me. And it's the number one thing that you can do to support this podcast is share it with a friend. Share it with a friend who would benefit from listening. Number two, before I go, I just had to tell you about something that I've been working on that I'm super excited about. It's my weekly newsletter. And it's called Try This.

Every Friday, yes, every Friday, 52 weeks a year, I send out an easy-to-digest protocol of simple steps that you or anyone you love can follow to optimize your own health. We cover everything from nutrition to mindset to metabolic health, sleep, community, longevity, and so much more. If you want to get on this email list, which is, by the way, free and get my weekly step-by-step protocols for whole-body health and optimization, click the link in the show notes that's called Try This or just go to Drew Perot.com. That's D-H-R-U-P-U-H-I-T-com and click on the tab that says, try this.