The Maudsley Deprescribing Guidelines: An Interview with David Taylor and Mark Horowitz

In this interview for MIA Radio, Brooke Siem speaks with David Taylor and Mark Horowitz about their publication of the Maudsley Deprescribing Guidelines, which is of particular note since the Maudsley Prescribing Guidelines is a leading text in medicine worldwide.

David Taylor is the Director of Pharmacy and Pathology at Maudsley Hospital and a Professor of Psychopharmacology at King’s College in London. He is also the editor-in-chief of the journal Therapeutic Advances in Psychopharmacology. Beyond academia, he contributes significantly to public health policy as a member of the United Kingdom’s Department of Transport expert panel that introduced drug-driving regulations. He is also a current member of the UK government’s Advisory Council on the Misuse of Drugs and is the only pharmacist to have been made an honorary fellow of the Royal College of Psychiatrists. David is the lead author of the Maudsley Prescribing Guidelines, a role he has held since their inception in 1993.

The Maudsley Prescribing Guidelines have achieved significant success, with over 300,000 copies sold across 14 editions and translations into 12 languages. David has also authored 450 clinical papers published in prominent journals such as The Lancet, BMJ, British Journal of Psychiatry, and Journal of Clinical Psychiatry. His work has been cited over 25,000 times.

Mark Horowitz is a clinical research fellow in psychiatry at the National Health Service (NHS) in London. He is a Visiting Lecturer in Psychopharmacology at King’s College London and an Honorary Clinical Research Fellow at University College London, in addition to being a trainee psychiatrist. Mark holds a PhD from the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London, specializing in the neurobiology of depression and antidepressant action. He is the lead author of the Maudsley Deprescribing Guidelines and an associate editor of Therapeutic Advances in Psychopharmacology.

Mark co-authored the recent Royal College of Psychiatry’s guidance on stopping antidepressants, and his work has informed the recent NICE guidelines on the safe tapering of psychiatric medications, including antidepressants, benzodiazepines, and z-drugs. He has collaborated with the NHS to develop national guidance for safe deprescribing for clinicians and has been commissioned by Health Education England to prepare a teaching module on how to safely stop antidepressants.

Mark has published several papers on safe approaches to tapering psychiatric medications, with contributions in The Lancet Psychiatry, JAMA Psychiatry, and Schizophrenia Bulletin. His interest lies in rational psychopharmacology and the deprescribing of psychiatric medications, which is deeply informed by his personal experiences of the challenges associated with coming off psychiatric medications.

The transcript below has been edited for length and clarity. Listen to the audio of the interview here.

Siem: Okay, here’s my first question. Who’s Maudsley? What is Maudsley?

David Taylor: Henry Maudsley was a psychiatrist in the Victorian era. The Maudsley Hospital was founded on the basis of a need for treatment of shellshock after the first World War. It’s arguably Europe’s leading institute for psychiatry research. It’s famous for the research that comes from it and the books published by people who work there. One of those books is the Maudsley Prescribing Guidelines, and one of them is the Maudsley Deprescribing Guidelines.

Siem: Thank you both for being here. David, you had a big hand in the Maudsley Prescribing Guidelines, correct?

Taylor: When I first started at the Maudsley in 1993, there was a guy called Rob Kerwin, a professor of neuropsychopharmacology. He had the idea of producing an evidence-based prescribing guide for mental health practitioners. We produced something in 1994 which we were very proud of. It’s 14 pages long and has almost nothing in it, but it was a start. Now, Most English-speaking countries use the updated editions as a guide to prescribing in psychiatry.

Mark Horowitz: David’s too shy to say, but it’s the most widely used psychiatric prescribing book in Europe, in the UK, in Australia. Every psychiatrist I know has a copy of the Maudsley. It’s a very widely used book.

Siem: The Prescribing Guidelines came out in the early ’90s, but it took 30 years to get the Deprescribing Guidelines. What brought you to write this book, and why is it important to you?

Horowitz: I’m from Australia originally. I moved to London to do a PhD at the Institute of Psychiatry. In 2011, I did a PhD in the neurobiology of depression and how antidepressants work. At the end of that PhD, I read a paper about withdrawal effects from antidepressants. At that point, I’d been on an antidepressant for 13 years.

I started antidepressants as a miserable third-year medical student, and I continued them for more than a decade. When I read that paper, I hadn’t heard about withdrawal effects which I found startling because I thought drugs that cause withdrawal also cause tolerance, which means they wear off over time. Also, drugs that cause withdrawal tend to have negative effects. For example, benzodiazepines are not widely used in the UK or Australia because of their toxic effects.

I wondered if the antidepressants were even effective after 10 years and if they were creating negative effects. I had fatigue, narcolepsy, and a lot of impaired concentration and memory, so I started to wonder if it was due to the antidepressants themselves.

So, I decided to try to come off my antidepressant. I read all the papers in my field and they all universally said the same thing: antidepressant withdrawal effects, which they call “discontinuation effects,” are mild and brief and you can stop in a few weeks with no major issue.

Then, because I’m a millennial, I went online to check what people had to say, and it was a different story. Some people got incredibly unwell coming off antidepressants, and it took months and years. I didn’t know who to believe because I’m an institutionalized person. I’ve got six academic degrees. I’m used to listening to professors. So I split the difference and decided to come off my 10 mg of Lexapro over four months. I halved my dose four times and used the equipment in my molecular biology lab to get a liquid and go down by a half every month, then a quarter, an eighth, and a sixteenth. I thought I was being pretty damn careful.

At a 1 mg dose, the floor fell out of my life. I started having trouble sleeping. I would wake up in the morning in full-blown terror, like I was being chased by a wild animal. This lasted throughout the day, for hours and hours. I ran until my feet bled because it gave me a bit of relief. I was dizzy and things around me felt dreamlike. It went on for week after week. I thought, “I can’t keep going on like this” and slowly went back on the medication. Over a few weeks, things settled down.

It was the scariest experience of my life, and nothing like the issues that put me on the drug in the first place. At that time, I was working at the National Psychosis Unit. I talked to a few academics and discovered this paper showing that very small doses of medication can have very large effects, and that’s why you might need to go down very carefully at the end, with the last couple of milligrams being the hardest to come off. A lot of different psychiatrists laughed at me and said, “These are homeopathic doses. How could you have trouble?” But when I went to talk to David Taylor, he instantly said, “That’s the law of mass action. When there’s not much drug in the system, every milligram of drug has a very big effect.”

I tried to come off Lexapro again in 2018. At that point, I understood that the leaders in my field had dismissed and minimized the issue. SurvivingAntidepressants.org had a lot more insightful advice. I followed what they recommended and found it much easier to come off my drug than before. Also, a lot of the issues I’d had with fatigue and concentration and memory started to get better.

I teamed up with David and we wrote an article published in The Lancet Psychiatry, where I outlined what I’d learned on these websites and combined it with some of the academic work that looked at the way the drugs affect the brain. That article led to increased attention to the issue in England. The Royal College of Psychiatrists got us to write some guidance for them on how to stop antidepressants. The NICE guidelines, which are the government guidelines in England, adopted our approach. I’m now working with the main pharmacy service in the country to put out this guidance to doctors and pharmacists.

David and I realized there wasn’t a definitive, authoritative book for clinicians on how to stop medications. We thought we’d write it. It took three years and hundreds of pages.

Siem: David, what is the story from your perspective?

Taylor: My journey is not similar, but it ends up at the same place. In my 20s, I had been treated with a range of antidepressants, without much success. In my 30s, I went on Effexor (venlafaxine). Once I was stabilized on that, I noticed I’d start to get withdrawal symptoms before my next dose was due. I took the pill, rather oddly, once every 21 hours. I had to do that to avoid the emergence of withdrawal symptoms, which would come on just after 21 hours, like clockwork.

I would start to feel a loss of balance, dizziness, a slight anxiety, and all of those things would get worse if I did not take the next dose of venlafaxine. As it happens, venlafaxine didn’t really help me, so I decided to stop taking it. I knew everything about stopping antidepressants, and I did it slowly, and I knew what the symptoms might be. What shocked me, though, was the severity of the symptoms. Even though I knew what was coming, and I knew the words to describe the things that I would experience, the experience of them was vastly different.

You can read “flu-like symptoms,” but you feel like you’ve got a pretty bad flu. That’s not great on its own, but then you read about dizziness, anxiety, irritability, mood changes, sleep disturbance, color intensification, and vivid dreams. I had all of those, and all of them I’d read about and all of them might have been mild or moderate, but together in constellation, it was horrible. And it was horrible for several weeks.

Then, my next instructive experience, which I ignored at the time, was that I got some funding for a helpline for patients in my department. We’d have patients ring in about their medication, we’d have expert pharmacists answer them. Occasionally I would man the line, and what we found was that the most common reason for calling us was people trying to stop antidepressants. We noticed that there is a subgroup of people who said that they had very severe symptoms and that those symptoms lasted for months, if not years. This is where my regret comes in because when I spoke to people, when I heard about people who were claiming to have had very severe symptoms, which lasted months or years, I thought that it was some kind of neurosis. I couldn’t quite bring myself to believe that it was a drug-induced effect or at least the stopping of a drug-induced effect.

I stored that observation away in my brain and as time went by, the patient line closed down and I heard more and more about people’s experiences with severe and longstanding withdrawal reactions. I came to be a believer. It’s not a common reaction to stopping antidepressants, but it’s common enough for there to be a huge number of people who have these very severe and extended reactions to stopping antidepressants.

It was a happy coincidence that Mark and I spoke at the National Psychosis Unit ward. Mark had the grit and determination to submit our paper to a very high-ranking, high-influence journal. It was the launch pad for us.

Siem: The detail in the book is unbelievable. How many drugs are outlined in the book?

Horowitz: There’s about 25 antidepressants, 25 benzodiazepines and Z-drugs, and two others. About 55 drugs altogether. The basic message is: It’s harder to stop drugs than it is to start them. The reason why it is so thick is because everyone’s a bit different. Some people have a fairly easy time coming off medication, and some people have a very hard time, which means there needs to be a lot of flexibility in how people come off. What takes up a lot of space in the textbook is different schedules for coming off for each drug—either fast, moderate, or slow—with advice on how to choose, how to adjust, and all sorts of troubleshooting to make it individualized. We tried to make it easy for any clinician or patient who wants to work with their doctor, and we do it for America, Europe, the UK, Australia and Canada.

Siem: Let’s talk about the law of mass action. What is it and why it’s important for psychiatric drug withdrawal?

Taylor: It’s tempting for most people to imagine that the relationship between the dose of medication and its effect is linear. For example, you might think that if you want to get 100% action from the drug you might take the maximum dose, and to get 50% of that action you might take half the maximum dose. But it’s nothing like that. The relationship isn’t a straight line that runs from the bottom left to the top right. The graph that describes the relationship is more like the one side of an arch. It’s quite steep when it’s near the ground and it curves over at the top until it becomes horizontal. That’s the shape of the relationship between the dose along the bottom and the activity of the drug on the Y-axis. As you increase the dose from nothing to very little, you get a rather large pharmacological effect, and when you go from very little to a little bit more, that increases massively.

When you get up towards the top of the arch, as you increase the dose, the pharmacological effect hardly increases. For many drugs when you’re on that flattened bit you can double the dose, but the activity of the drug might increase from 98% of the maximum to 99% of the maximum.

Siem: That steep drop-off happens so much earlier than the strength of the drugs on the market, if that makes sense. Is there a conclusion to be drawn that, when people’s doses go up and up, it’s not having any more effect?

Horowitz: You put your finger on it. That steep bit of the curve happens below the smallest available tablet for most medications. The smallest dose for Effexor is 37.5 mg, and for citalopram (Celexa), it’s 10 mg or 20 mg, and for Lexapro it’s 5 mg or 10 mg. Doctors and pharmacists in general think, well, it’s a very low dose. What they mean by that is that it’s the smallest tablet available. But in terms of effect on the brain, it’s not that low a dose because of that steep curve, and so when people are told to halve their tablet and then stop it, everyone thinks they can just step off. But because of this steep curve, it’s like walking out the seventh-floor window. You think it’s at the bottom, but you’re still kind of high up on the building. Then, when people fall out of a seventh-floor window, doctors say, “If you’ve had trouble coming off such a low dose, you must need the drug.” They don’t see that the patient has come down from this high level, and that’s why a proportion of people on long-term antidepressants need doses beyond commonly available tablets, whether that’s a liquid version of the drug or compounded capsules, or some other way of making up smaller doses.

Siem: You came to this conclusion through the PET scans, correct?

Horowitz: The forums recommended coming down by 10% of your dose every month, and I didn’t know why that made sense. Going down in smaller amounts makes sense, but why would it get smaller and smaller? Then I came across this nuclear imaging that gave people different doses of medication and scanned their brains to see how big an effect it had on their receptors and it followed the same arch David explained. It exactly matched what the patients had worked out by trial and error.

Siem: Are there any precautions or limitations that people new to this topic should be aware of when using the Maudsley Deprescribing Guidelines as part of their practice?

Taylor: A core principle is that the process should be patient-led rather than clinician-dictated. It’s the patient who’s experiencing the withdrawal. The tapering regimen should be tailored and adjusted to the patient’s experience, and that works in both directions. It should be slowed and more hyperbolic in people who have severe and longstanding reactions. It may be quicker and shorter in people who have very limited reactions. It’s worth saying there is a group of people who seem to be able to stop antidepressants without any problems at all.

There seems little point in prolonging the withdrawal phase of the medication, especially given that abruptly stopping antidepressants doesn’t make relapse more likely. The whole field is rather confused because of withdrawal reactions mimicking relapse, but what I’m trying to say is that there’s a good reason to go slowly even with people who don’t have a severe reaction, because they’ll probably benefit in the longer term.

Siem: It’s also a book I would recommend to the family members of somebody who’s in withdrawal because it can help them understand, in plain language, what we think is going on.

Horowitz: There are a lot of misconceptions about this material, and I wanted to correct them. What should doctors be aware of when they crack the book open? There’s an increased understanding that there are withdrawal effects from antidepressants, but people still don’t quite get their heads around protracted antidepressant withdrawal. David said that when he first heard about it, it sounded like the product of a neurotic mind. If I had encountered this stuff in inpatients, I would have had David’s exact reaction. I was taught antidepressants are as safe as Advil or Aspirin, so I would have thought it was a bit odd that people were in bed for months with dizziness and panic attacks. A lot of my colleagues still think that, and I have some sympathy for them because it sounds so out of left field. If I hadn’t had firsthand experience, I don’t think I would have had enough insight into it to believe it. I understand the skepticism from my colleagues. It doesn’t fill me with pleasure, but I understand where it comes from.

Part of the point of the book was to try to explain some of this. For example, the textbooks say that withdrawal should come on within three to four half-lives of a drug because the drug has left your system The half-life of most antidepressants is about a day, so it should come on in a few days, but often, that’s not what happens.

I started seeing people coming in a few weeks after stopping an antidepressant with withdrawal effects like electric zaps, dizziness, headache—really classic withdrawal symptoms. I first thought, “This can’t be withdrawal. It can’t come on weeks afterward.” I saw several cases, and I thought it wasn’t typical.

Now, there are a couple of things that make me believe that it is withdrawal. First, there’s an imaging study that shows that the brain elimination time for antidepressants can actually be weeks. Although the half-life in the blood is a day for most antidepressants, it seems to leak out slower from the brain. I don’t know if that means it’s sticky in the central compartment, but it does make sense as to why it might take weeks for withdrawal to come on.

In another study, the time to withdrawal onset averaged four weeks in a group of patients and the standard deviation was 13 weeks. In other words, some people in this group experienced withdrawal effects that came on months after stopping. There’s clearly more variation than the textbooks indicate, and that causes a lot of confusion.

Second, there is protracted withdrawal syndrome. Patients come in and say, “I stopped my antidepressant three months ago. When I stopped it, I developed terrible symptoms like panic attacks, terrible mood, and I’m still there three months later.” The doctor says, “Well, the drug is out of your system. It’s been out for weeks. It couldn’t be because of the drug. This cannot be withdrawal. You must have developed a new-onset panic disorder or maybe you’ve developed multiple sclerosis, we need to send you to a neurologist.” That’s what happens. People get sent around to specialists where they get told they’ve got a mental illness and they should take more medication. I might have believed that as well, but now I see many, many people with those long-lasting symptoms.

The way it makes sense to me is the brain adapts to the drug when you’re on it. If you take a drug that increases serotonin, your body will become less sensitive to serotonin. It adapts because of homeostasis. When it’s too hot outside, we sweat. When it’s too cold outside, we shiver. If your brain is exposed to too much serotonin, it becomes less sensitive to serotonin. You can see that in just a few weeks of being given an antidepressant on brain imaging. Now, when you stop the antidepressants, your serotonin levels go back to normal. But your brain doesn’t just snap back into how it was before the drug was there. Those adaptations, those changes, take a while to get back to normal. In fact, in one study, after stopping antidepressants in patients, there were changes in the serotonin system for up to four years after stopping.

In animal studies, findings are similar: after stopping antidepressants, there are changes to the hormonal system and the serotonin system that last for more than a year in human-equivalent time. The analogy that comes to my mind is when you go to a loud concert, your eardrums become less sensitive to sound. If you walk out into a quiet street, people around you sound muffled for a few minutes. That’s actually a sound withdrawal syndrome. Now, when you shut the door on the concert, the sound disappears in a second, but it takes a few minutes for your eardrum to readapt to normal levels of sounds.

The same is true for exposure to psychiatric drugs. When you stop them, your liver and kidneys metabolize them in a few days or weeks and they’re out of your system. But the adaptations that your brain has made to the presence of those drugs can last, we think, for months or years. That is probably why withdrawal syndromes can last for so long, because of the residual effects on the brain after stopping the drugs. That’s why they can last longer than the drug takes to leave the system.

We haven’t done much research into what causes protracted withdrawal. It hasn’t been seen as a legitimate condition. There hasn’t been brain imaging or the study of hormones, so we don’t know. But I think it’s pretty clear that people’s nervous systems are affected because they get neurological symptoms, they get psychological symptoms, they get bodily symptoms, so something is clearly going on. We know that these changes can stick around. We think that that probably occurs more often if you come off too quickly. It’s a good reason to come off slowly just to avoid the risk of that happening to you because I’ve seen it. I’ve got an inbox full of people with that condition, and it really upends their lives. It can be absolutely devastating for some people.

Siem: How do the Maudsley Deprescribing Guidelines handle polypharmacy? What do we do when a patient is on two or more drugs?

Taylor: We skirt it to a large extent. It’s covered more in the Maudsley Prescribing Guidelines, but even there, it isn’t covered in any depth. The number of combinations in polypharmacy regimen trends toward the infinite. It’s almost impossible to create or gather a report on any information on particular combinations simply because there are so many different variations of those combinations.

Siem: Are there any loose guidelines regarding polypharmacy that you have noticed clinically?

Horowitz: We’ve put in two broad principles. First is to either think about the drug that has the most harm compared to benefit, or to think about the drug that’s easiest to come off of. If someone has a very strong feeling that they want to stop one drug over another, then the person’s preference should be primary. If they’re not sure, you might look at a series of drugs and work out which might have some benefit for them or no benefit and which ones are causing the most harm. The other approach that I often take is it’s nice to be able to have a win when a patient wants to come off medications. It’s nice to choose something easy. You might choose a drug that’s easiest to come off, and that’s often the drug that’s been started most recently.

Siem: Mark, you have dealt with your fair share of pushback doing all the work you’re doing. I’m wondering how the Maudsley Deprescribing Guidelines has been received amongst prescribers, and what has your experience been with the actual publication of the book?

Horowitz: As with all my work, it’s been very mixed. Some clinicians and psychologists have said having a guideline has made their practice more streamlined. Mainstream academic psychiatrists have mostly ignored it, but a lot of GPs, pharmacists, and nurses have written to me and said that they use it in their clinics, but that there are practical barriers.

A lot of patients have bought the book. In some ways, I feel that it’s a little bit sad that the patient had to buy the book to give to their clinicians. I wish that doctors would have an interest in it, because obviously, I think being a good doctor is knowing how to start medication, knowing when to stop, and how to stop. I think it’s part of good quality practice. But patients have taken it upon themselves to try to get clinicians on board.

Taylor: I get people writing to me, emailing me, thanking me. I keep an eye on the Amazon reviews. Most of those are very positive. Although Mark and I wrote the book for clinicians, it’s interesting that almost all of the reviews on Amazon are from patients. I haven’t had much in the way of negative feedback. Part of the reason for that may be that a lot of people in the field of psychiatry have this kind of semi-delusion that I know what I’m talking about, so they might be wary of challenging me in my own field, so to speak.

Although I will be happy to be challenged on it, I don’t want people to run away with the idea that I’m anti-medication, anti-psychiatry, or anti-antidepressants. I’m not at all; I’ve taken lots of psychotropics, sometimes with considerable success. But I do think there needs to be a balance between the massive amount of promotion that there is funded by pharmaceutical companies to start these medications, and what limited information there is on how to stop the medication. As Mark rightly points out, that’s as important if not more important than how you start them.

Siem: I think it’s amazing that so many patients are taking it upon themselves to get this book because for so long, so much medical research has been behind paywalls. I see that as a huge, huge win.

Horowitz: Some parts of it are a bit academic, but it is written in a way that any informed member of the public could understand it. We foresaw that a patient ideally would be working with a clinician and would be able to inform themselves about what’s the best way to come off their medication. More and more in the modern age, patients are taking their health into their own hands and informing themselves. I think this could be, in part, why we kept the language open to being understood by the public. I think this could generate conversations between patients and their clinicians about what would be the best way to come off medication.

Siem: To close, I would love you two to dream a little bit. Where do you hope the research around withdrawal goes? Where do you hope we’re going with all of this and what can people do to continue to spread the good word?

Taylor: We produced a book, which for each drug has three different ways of stopping the medication. I would like research to help us define regimens for withdrawal that enable people to stop antidepressants with as few problems as is physically possible. That would make a huge difference to a huge number of people in the world. The use of antidepressants is astronomical. There are millions of people taking them around the world, and those millions of people will ultimately have to stop taking them. I would hope that research will tell us exactly how we can get people stopped with as few problems as possible.

Horowitz: First of all, we’re doing research in Australia to look at whether stopping in this hyperbolic way improves over stopping the old-fashioned way. A lot of studies suggest that it will, but it will be good to show it because that will influence guidelines around the world, which like to see randomized controlled trials. Then the next step is to individualize for people so there’s not all this trial and error. Because at the moment, there definitely is an aspect of trial and error. It’d be great to take away that sort of uncertainty away from people.

I’m very interested in knowing what’s happening in people’s brains on long-term medications. Are there ways to reverse it? Is it better to give people short-term medication to avoid some of those long-term consequences? Is there any intervention to help people who suffer from these protracted withdrawal syndromes? I think a lot of the research that suggests people should use long-term medication is flawed because withdrawal effects aren’t taken into account. I’d be aware that a lot of the guidelines recommend long-term antidepressants and other drugs from studies in which they stopped very quickly. They found the people who stopped them felt worse. No one ever looks at withdrawal effects. It could be that actually, the reason why people feel worse is because of withdrawal, in which case the drugs are not quite as effective at preventing relapse as people think. I think a lot of those studies need to be re-looked at and withdrawal taken into account so that might have quite a big influence on what the results of trials are.

Siem: Wonderful. Thank you so much. Do you have any closing remarks or any asks of the audience?

Horowitz: To any clinicians, I would implore you to try stopping medications more slowly, especially at the end, and using things like liquids to make it easy for patients. It’s very gratifying as a clinician to see people come off the drugs that they thought they couldn’t stop. I hope other clinicians out there get that experience.

Siem: Mark and David, thank you so much for being with us today. Again, the book is the Maudsley Deprescribing Guidelines and it can be found on Amazon. Thank you both. Keep up the good work.

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