The Truth About Antidepressant Withdrawal Symptoms

Mark: 
To use analogies to make it simple, I think about a heavy rock sinking into wet mud. It sinks more and more, each week or month. And so if you take it out in 10 years, it’s really hard to pull out. It’s pretty easy after a couple of hours. And so that’s a general law of pharmacology, of drugs that affect the brain drugs that cause withdrawal.

The longer you use them, the more severe, long lasting, and common withdrawal effects are.

Bret: 
Welcome to The Metabolic Mind Podcast. I’m your host, Dr. Bret Scher. Metabolic Mind is a nonprofit initiative of Baszucki Group where we’re providing information about the intersection of metabolic health and mental health and metabolic therapies such as nutritional ketosis as therapies for mental illness.

Thank you for joining us. Although our podcast is for informational purposes only, and we aren’t giving medical advice, we hope. We will learn from our content and it will help facilitate discussions with your healthcare providers to see if you could benefit from exploring the connection between metabolic and mental health.

If you’re taking or thinking of taking an antidepressant, it’s important to know the risks and the benefits, and one of the risks could be what happens when you eventually want to come off the medication? What is the risk of withdrawal? Because just because you start a medication doesn’t mean you have to take it forever, right?

What is that risk? A new paper was just published suggesting that risk is very small, that the risk of discontinuing antidepressants is extremely mild and not even really clinically significant. But is that true? I’m joined by Dr. Mark Horowitz, who’s an MD PhD. He’s a psychiatry researcher and he specializes in withdrawal from medications and runs a clinic called Outro Clinic that really specializes in this.

And he has some problems with this study, or concerns with this study, about the short term nature of it, and it’s a very different perspective about what the potential risks of coming off antidepressants are. So I hope you really enjoy this interview. It’s really enlightening to have this sort of different perspective from maybe what a lot of people are reading about the conclusions of this study.

Many of the interventions we discuss can have potentially dangerous effects have done without proper supervision. Consult your healthcare provider before changing your lifestyle or medications. In addition, it’s important to note that people may respond differently to ketosis and there isn’t one recognized universal response.

Dr. Mark Horowitz, welcome back to Metabolic Mind. It’s good to see you again. 

Mark: 
Good to see you again, too, Bret. 

Bret: 
Yeah, and I’m excited to get into this study with you because, gosh, looking at Twitter, there’s been so much controversy about this meta-analysis of studies looking at the severity and the impact of antidepressant discontinuation.

But before we get into that, because I know you’ve got a lot to say about it, but before we get into that, give us just a brief summary of your background, how you got into this field of medication tapering and discontinuation, and why it’s so important to you. 

Mark: 
I’m on both sides of the desk on this.

I started my training as a psychiatrist in Australia, and in the UK. I did a PhD in How Antidepressants work at the King’s College London. And I also was a patient who took antidepressants for many years. I was a miserable young man in my early twenties, and I was given Lexapro escitalopram. I tried to come off it now several years ago in a way that I thought was quite slow, much slower than what guidelines said, and 

I had the worst experience of my life. Basically, I developed what I now realize was, I think, mild to moderate akathisia. I was full of terror. I had panic attacks that lasted for hours and hours of a day. I had not experienced that before in my life. I didn’t think it was anything like the issues that had put me on the drug in the first place.

I understood it was withdrawal. That was a big surprise to me. I had not been taught about that in my training. I’d all the guidelines at the time said it was mild and brief. When I found out that it wasn’t just me, it was tens of thousands of other people who had been forced to go onto online peer support groups.

I realized that there was a significant issue, a mismatch between what guidelines said and people’s experience, and that got me very interested. As Nietzsche said, pain is the major teacher I got. I got a very painful lesson. And that’s what has motivated me to try to work out what’s going on here and how can we help people to avoid the issues that I went through.

Bret: 
Yeah. and it’s such an interesting position to be in when you’re learning this. You’re getting trained in this and everything you’re reading and being trained, mild and short-lived and not a big clinical concern, but then your personal experience and the experience of thousands of others is directly at odds with that, which really is an uncomfortable feeling.

It is uncomfortable for you, I’m sure. And you’re, like you said, you’re on both sides of the equation as a learning and practicing psychiatrist, but then experiencing this I guess one big question is, and it could be a long question, but what, why the disconnect?

What do you think is the big reason for the disconnect? And then we’ll see how that applies to this study. 

Mark: 
So that’s, it took me a while to work out what the disconnect was, you’re right. And as you say, it was a bewildering experience for me because. I’m a very institutionalized person.

I’ve got six academic degrees. I’m used to memorizing textbooks and learning from professors from Ivy League universities and the equivalent in the UK and Australia. I spent, like any doctor, spent a lot of time memorizing things from textbooks. So I was bewildered that I had this firsthand experience.

It was mirrored by lots of other people and it didn’t match what was in guidelines. And then I began to understand by reading different books and papers about what had happened. And really the setup is the following. The drug companies that got their drugs approved antidepressants did eight to 12 week studies in order to get past the regulators, the FDA and the MHRA and other around the world.

And these regulators demand that you show two positive studies that beat placebo over about eight to 12 weeks. And so these companies did many of these studies. And in some of the studies, they stopped antidepressants after that eight to 12 week exposure. And what those studies mostly showed was mild and brief symptoms.

It’s worth noting that not true for everybody. In some studies given people given sertraline, Zoloft and especially venlafaxine or effects saw already after eight weeks of exposure, some people had extremely severe symptoms coming off. So I don’t want to say that it’s nothing for everybody on short-term treatment, but it is true to say that for most people after eight to 12 weeks of exposure to antidepressants, there are mild and brief symptoms.

I think that’s a fairly accepted, well-documented statement. The companies published those papers, they distributed them widely to psychiatrists, key opinion leaders around the American, around the UK. And because there was a dozen such studies, when guideline committees came to write the guidelines, they wrote down that withdrawal effects or the discontinuation symptoms, which is the preferred industry euphemism for withdrawal, are mostly mild and brief.

Now, in the guidelines, they didn’t say mostly mild and brief for people who’ve been on the drugs for eight to 12 weeks. They just said mild and brief. And the reason why I don’t, I think it’s fairly innocent. They only saw studies that showed mild and brief symptoms, and so they were reflecting what the study showed now, the problem with that is like for any drug, the longer you take it, the more you get used to the drug and the harder the more withdrawal effects you get when you stop it. If you drink coffee for two days, there’s no issue stopping it. If you drink it for 10 years, there’s bigger issues.

And the same is true for opioids, benzodiazepines, any drug you care to mention, and what is probably happening there is, you are getting more and more used to accustomed to the drug. Your brain and body are adapting to it, and when you come to pull it out, it’s harder. I to use analogies to make it simple.

I think about a heavy rock sinking into wet mud. It sinks more and more each week or month. And so if you take it out in 10 years, it’s really hard to pull out. It’s pretty easy after a couple of hours. And so that’s a general law of pharmacology, of drugs that affect the brain drugs that cause withdrawal. The longer you use them, the more severe, long lasting. and common withdrawal effects are. 

Bret: 
And that makes a lot of sense. And then so applying that to this paper, in a way, I guess you could say it’s more of the same, but, so the paper’s called Incidents In Nature of Antidepressant Discontinuation Symptoms, and it’s a systematic review and meta-analysis published in JAMA Psychiatry.

And the main conclusion is more of the same brief and mild. So there were statistically significant increase in symptoms, but it was determined that those were not really clinically significant, and did not constitute a significant withdrawal effect. Now looking at the details of the study, actually, I mean it gets a little confusing, so I’d love to have you help clarify because they say they use 50 studies, in the analysis, but then they have a whole bunch of different conclusions that they draw and it sounds like the main one was based on 11 studies and so it’s different because some of the 50 studies that they included had longer term studies.

That’s true. Yeah. But as you’ve pointed out on social media and the 11 studies, they were basically all shorter term studies, so, tell us a little bit about the setup and the conclusion of the study and that difference between the 50 and 11, if you could. 

Mark: 
So I’ll just lay out what they did. So they set out to look at studies that had looked at withdrawal effects from antidepressants and compared them to either people who had stopped a placebo that’s control or continued an antidepressant.

So they’re trying to isolate what’s just due to the drug and what’s due, there’s obviously psychological factors that might play in a role, and so they’re trying to work that out. They did a search and they found 50 studies and they included 49 in different meta-analyses. There were two main studies that they did here.

One was looking at the overall withdrawal effects. And when you say it didn’t meet a significant threshold, that’s what you’re talking about. That was the main finding that after a week, the average increase in withdrawal effects in the group that stopped antidepressants compared to control groups was 1.08 symptoms.

That was what they said the threshold is normally four symptoms, 1.08 is less than four. And so this is not a significant withdrawal syndrome. And that was the main, that’s been the main takeaway of the paper. When you see headlines in papers saying there’s not significant withdrawal syndrome, that’s what they’re talking about.

That particular analysis, yes, only used 11 studies in the meta-analysis so the other 38 odd, although there’s some overlap. So there was 45 studies that they used to look at individual symptoms. So they looked at how common is dizziness, how common is nausea and nervousness, which we can talk about, but that was not, that was a, it was a part of what they did.

That was not the main analysis that they announced in their press release and in all the media around it. So the subset of studies that they used for the main analysis was 11 studies. Those 11 studies went for eight to 26 weeks. 10 of them went for eight to 12 weeks. So these actually are, I talked at the beginning.

Guidelines are based on these eight to 12 week studies. Some of the studies included were those original eight to 12 week studies that guidelines were originally based on. So it’s a little bit of a sense of deja vu here. This is a never repetitive story. The 26 week study, you probably think, oh, that sounds a bit longer, and it is. But that study was looking at an antidepressant called agomelatine, which is sold as Valdoxan. I don’t think it’s even approved in the US so you probably have never heard of it, but it’s a bit famous for not having a withdrawal syndrome. It acts not on serotonin and not on norepinephrine.

It’s a different sort of drug and it doesn’t have a withdrawal syndrome. So the single study that went for 26 weeks is with a drug that no one thinks causes withdrawal. So it’s a bit irrelevant. So in essence, the main analysis was based on 10 studies that went for, that had people on antidepressants for eight to 12 weeks before they stopped.

So it’s exactly history repeating. Were back to the original studies done by drug companies that the analysis is based that they’ve based their analysis on. 

Bret: 
Yeah. And that gets frustrating I think when you repackage old studies and try and present it as new data, and look what we now have found and have proven.

But if you look at the debates on social media, you say, look, this is the meta-analysis of randomized controlled trials. This is the pinnacle of research quality as opposed to saying, you’ve pointed out that you have survey data, right? That is really impactful for people’s individual experiences.

But if you’re just looking at it from an academic standpoint, they don’t compare. But when you break it down to the specifics, they are so different and represent so such different populations. I guess the question is what are we missing? is there longer term data that isn’t included in this meta-analysis that should have been?

Or is that something that we need to make sure is studied and done in the future so that it could be included? 

Mark: 
Yeah, so there’s a few points to make there. Number one, I agree it is frustrating to see old data repackaged. because this is exactly this. All the press release and the media said this is a meta-analysis.

It’s done very well. It’s in a big journal, and in a lot of respects, it was done well. They looked at the quality of studies. They did a risk of bias assessment. They did a meta-analysis using latest techniques. So there are a lot of good things there, but they are looking at eight to 12 week studies.

It doesn’t matter how brilliant the techniques you use, you’re still looking, I would say, the old sort of joke, the drunk is looking for his keys under the lamplight because that’s where the light is. If you’re looking there, you’re not gonna find the issues, which are of course, what happens to long-term, people on long-term use of antidepressants.

It’s not true. Sorry, I just say on the survey data things, I talk about a survey that we did. Not to say that it’s a fantastic representation of the risk of withdrawal effects because it’s not, it could be a self-selected sample. That’s the problem with surveys. I point to that to show, it clearly shows what’s called a biological gradient.

You know that the longer you’re on a drug, the worse withdrawal effects. And a survey is a perfectly reasonable place to find such a thing. So for example, there are no randomized controlled trials showing that smoking causes lung cancer. It’s not ethical to randomized orders smoking. It is found dose response relationships are found from surveys.

People that smoke more cigarettes have more lung cancer. And yes, there are lots of other factors, but if you control for them, you can see that. And we saw something similar. So that’s why surveys were introduced. But there are long-term studies that are randomized controlled trials that are double-blinded.

That should have been included in the main analysis in this study as far as I can see. So there are three studies that come to mind. Rosenbaum 98, Judge 2002 and Mickelson 2000. They involved people who’ve been on antidepressants for four to 12 months. They were done very well by drug companies.

Like all these other studies, they were taken off their drugs. There was control conditions with people who continued their drugs. It was all double blinded. They carefully measured withdrawal effects using the DESS, this scale that is focused on in the calfas, meta-analysis and it showed huge levels of withdrawal. The average number of DESS symptoms coming off Peroxetine was eight. Coming off sertraline. Zoloft was five.

The proportion of people that had a withdrawal syndrome was 60% for Zoloft and 66% for Paxil. And that’s, I don’t know why that didn’t include that Rosenbaum study in their analysis, but it clearly shows incredibly high levels of withdrawal in longer term users.

So there are, those are not surveys, those are randomized controlled trials. And so they did what is interesting is the Rosenbaum study was captured in those 49 studies in their paper, and it is included to look at the individual risk of symptoms. So they did have the data. I’m not exactly sure what the rationale was for not including those much higher rates of withdrawal in their primary analysis.

Bret: 
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Now, back to the video. It’s really important to notice that those data do exist, and that they are contrary to what the, I guess, the conclusion of this paper is. that’s really important. But I guess another question is, why is it so important? And part of the reason is determining withdrawal from a recurrence of the depression that required the treatment, which is so important and of course, I’ve been trying to read all the conflicting views, but one is, if you call everything withdrawal, then that’s your only tool in the toolkit, and you have to recognize that there’s a recurrence of symptoms. so how did they try to differentiate in these studies?

What is a discontinuation effect of the me from the medication and what is a recurrence of their initial symptomatology of depression? 

Mark: 
So it’s a very interesting point because they focus on this issue a lot in their reporting of the study. So they argued that they didn’t find much depression as a withdrawal effect.

And therefore if people get depressed after stopping an antidepressant, it must be relapse or return of their underlying condition and that was one of their kind of major talking points in their press release. And what they’ve done is if you look down in the, I mentioned the secondary analysis, they looked at individual symptoms.

One of them is depressed mood. They looked at five studies, and they found very low levels of depressed mood, both in the control group and in the people coming off antidepressants, something like one and a half percent and there’s no difference. And they say, so we didn’t detect depressed mood. The trouble with what they’ve done is some of the studies they’ve, so it’s very, it’s a small number of studies they’ve used.

Most of some of those studies have used what are called spontaneous adverse effect reporting. That means if you’re in the study, you’ve got to contact the research and say, I’m feeling depressed, please put that down on my notes. They don’t assess it systematically. So systematic assessment would be every patient, every participant in the study will give you this questionnaire, will ask about depression again as it happens, there is a study that’s done that extremely well after longer term use.

It’s the Rosenbaum study. It’s a very good study worth reading. And they did something very careful. They took people who were on Zoloft, Paxil, and Prozac, they stopped their drugs for five to eight days and they measured withdrawal effects and depression scores at the same time, which is very rarely done.

And you can see Prozac doesn’t go up at all in terms of withdrawal effects because it’s got a long half life, takes a while to leave the body, and five to eight days is too short for it to come up. So it acts as a very useful control. Zoloft shot up five or six points. Paxil shot up eight or nine points, and the depression scores exactly matched that.

The depression scores didn’t go up at all. They were very much for Prozac. They went up quite a lot for sertraline, Zoloft, and even more for paroxetine, so that they were based on their criteria, they found that 30% of people on Zoloft met the criteria for relapse on depression. 36% met the criteria for Paxil.

On this depression score, and then when they gave the drugs back, the withdrawal shot to zero, and so did the depression scores. In other words, what they’re telling. A story of is that the increase in depressed mood is being driven by withdrawal. The degree, because you think about it, let’s say that, let’s assume that antidepressants are a bit effective for depression.

When you stop them, you might see a bit of an increase in depression because the depression’s coming back. But antidepressants improve depression scores by about two points. But on these studies, when you stopped antidepressants. The, depression score shut up by way more than two points, by, I think eight and a half points for Paxil and five or six points for Zoloft, exactly similar to the increase in withdrawal effects.

And they went away as soon as the drug was put back, which is not very typical of depression. In other words, this study shows this sort of parallel increase in withdrawal effects and depressed mood. It’s making the argument that depressed mood is a very common withdrawal effect from antidepressants and other studies.

Also, back that up, that’s what I see all the time clinical practice. 

Bret: 
And that’s confusing for the individual because I’m thinking if an individual is trying to come off an antidepressant and they’re trying to determine for themselves am I having a withdrawal effect or am I having a recurrence of my depression?

If depression is also a withdrawal effect, that makes it very hard to determine, what the symptoms are. Because one would be, hopefully, over time it will get better, whereas the other is you may need to go back on your antidepressant or have other therapeutic approaches to address your depression.

So how is someone to tell the difference? 

Mark: 
So it’s a really good point and that’s part of the confusion in the field. I think there’s a few things to step back and how do you distinguish these things. I think number one, just zooming out. Most people are put on an antidepressant in the context of something going wrong in their lives.

Divorce, job loss, being a young person, not being able to work out what to do with your life moving cities, death of a loved one. All sorts of things go wrong. And so a lot of people, the idea of a relapse isn’t very plausible. As a first pass, if you’ve got divorced and become very depressed and you come off your drugs five years later, it’s very hard to have a relapse of divorce possible.

Some people do it, but in general, so this framing of depression as this like lifelong condition that relapses when you take away a drug is trying to compare it to asthma or something like that is relevant for. But mostly we feel awful when our lives are awful. We feel okay when our lives are better.

So the idea of relapsing into your early twenties being confused or whatever it is already a little bit wouldn’t be your first thought, but of course that’s a lot in medical education. So that’s the sort of broad point. Then on more specific points, the timing of symptoms matters.

So if things come back in a few days, it’s very likely to be withdrawal. There is a thing that confuses a lot of people though, which is delayed onset withdrawal effects. So when I first saw this in patients, that they were coming off antidepressants, six weeks later, they developed brain zaps and headache and dizziness.

I thought that is very strange. The textbooks say three to five, half lives should be a few days with these short half-life drugs. But I saw symptoms weeks later. I don’t know exactly what causes that, but I have seen it so many times. It’s now recorded in various studies. There’s one study that finds that the average time to onset for people stopping SSRIs is actually four weeks with a variation of a few months.

I imagine it’s something to do with downstream effects, having to build up to some threshold before they manifest. I don’t pretend to understand the biology of it. That’s one issue. The second issue is the nature of the symptoms. So if you stop your antidepressant and you become dizzy and have headaches and you feel depressed, then it’s very likely that it’s a withdrawal syndrome.

It’s the old Occam’s razor. If you have a running nose and a cough and a temperature, it’s most likely that those are three aspects of the same condition rather than three different conditions. And the physical symptoms really make it simpler. Headache, dizziness, brain zaps. No one thinks that’s because of anxiety and depression.

But I will say the most common withdrawal symptoms are psychological. I think maybe people find that a bit hard, but you think about coming off alcohol or benzos, you feel terrible. Yes, you can get physical symptoms, you feel terrible. And we’ve seen a study after study that anxiety, low mood suicidality are common symptoms of withdrawal because you can see them even in people who were put on antidepressants for reasons other than mental health conditions that put on it for pain, for the menopause or even in healthy volunteers. And so what I always ask patients is when you went on the antidepressant, what did you have?

And they say, if they say I was lethargic, I was sleeping all the time, I was really depressed. What did you have when you came off the drugs? If they say, I was anxious, I was panicked, I couldn’t sleep. Those are very different symptoms. It could be that coincidentally, they’ve developed a new onset panic disorder on just the day they stop their antidepressant, but that’s a bit implausible.

What’s more plausible is they’ve developed quite common withdrawal effects, so I do a lot of before and after, and those are the main, those are the main ways of telling. 

Bret: 
Yeah, that’s a good point, and I’m glad you brought up the specific symptoms because in this study, they said the most common symptoms were dizziness, nausea, vertigo, nervousness.

And then they talked about the electric shock type feeling. So like you’re saying, those are usually not the depression type symptoms that someone was started on the medication for. And those are more indicative of the withdrawal and you talked about it, maybe just, the majority of the people who were started on an antidepressant for a reason, but I think we also have to acknowledge there is this subset of people who just have sort of a depressed mood without a specific trigger. Do you think those are the ones who are more likely to develop relapse as opposed to withdrawal or maybe unfortunately to develop both relapse and withdrawal, even though it goes against Occam’s razor? If they try to taper off for that specific population. 

Mark: 
Maybe, yeah, maybe those people are more prone to relapse, if you’re still in the same situation, if you’re still in the difficult relationship.

Job. Financial insecurity. Yes. That’s more likely to relapse. I guess the other issue is are antidepressants very good at preventing depression or relapse in the long term? And the evidence doesn’t support that. They have minimal effects in the short term. The overall effect of antidepressants is two points on a 52 point depression scale compared to placebo.

There’s all sorts of ways that, the way they do those studies, inflates the effect of antidepressant. So everyone agrees that the average effect of an antidepressant is pretty small. Drugs tend to wear off over time. Most drugs do. Benzodiazepines can make you feel pretty good in the short term, but wear off, so do opioids.

Drugs that cause withdrawal also cause tolerance. Those are flip sides of the same coin. The more that heavy stone sinks into the mud, that’s tolerance. The harder it is to pull out at the end, that’s withdrawal. So the small effects of beginning are very likely to wear off. And so when you see studies that save your stock on antidepressant, there’s a lot of relapse.

It looks peculiar that a drug that has marginal effects at the beginning suddenly has quite a large effect. When you stop it, you know that’s not what drugs do. Drugs wear off over time. They don’t get more effective over time. That’s the opposite. And a lot of people think the reason why those studies in which drugs are stopped people show relapse is probably because it’s withdrawal effects being missed, classified as relapse.

As that study I mentioned earlier on made really clear, because I just so asked that Rosenbaum study, 30% of people have sertraline met the criteria for relapse, 36% for paroxetine. It happened in that study. They measured withdrawal effects, but imagine they didn’t measure withdrawal effects. You just see a lot of depressed people, you’d be thinking, oh my goodness, people need their drugs.

And, of course, that’s what most studies do. They stop the drugs. They don’t measure withdrawal effects, and they just report that people get depressed. I think that there is scant evidence that antidepressants prevent relapse in the long term from existing studies. 

Bret: 
Yeah, and I guess the, so really the overarching theme here that we also should address is our antidepressants the best treatment or the only treatment.

Obviously they’re not the only treatment and there’s a lot of debate about whether they’re the best treatment. But then what else can we do if someone wants to try augmented therapy or to taper off? Of course we talk a lot about lifestyle interventions, about metabolic therapies and how those can potentially help and hopefully research. We’ll start investigating that so we can learn more about it, but what are your thoughts about augmenting someone’s antidepressant treatment and helping them come off? What lifestyle interventions do you feel can be most impactful? 

Mark: 
So again, I’ll just step back for a second. I think this is one that we’ve reified depression in our culture, which means we talk about it like it’s a thing, like heart disease or asthma.

But we know sort, I go back to simple things that my grandmother would’ve said, when life is awful, we feel bad. That makes us understand what’s going on. So if we are feeling bad because our relationships are unsatisfying or full of conflict, if our work is unsatisfying, if we have financial problems, the solution to that is to try to solve those problems.

It doesn’t mean it’s easy. Of course, I’m sitting here glibly on a podcast. You can’t wave a wand, but it’s good to identify what the issue is because otherwise you may not be aiming at the right target. I think that the answer is, it’s different for everybody. When people ask, how do you fix depression?

It’s a bit like saying, how do you fix people that is satisfied with their life or unsatisfied with their lives or overwhelmed by their lives or don’t have their emotional needs met? Got to work out what’s going on to try to work out what makes sense for an individual person. If you then want to go into what is generally helpful, that’s a slightly more generic conversation.

There are lots of things I always refer to the NICE guidelines in the UK. That’s a UK government department that assesses evidence to look at what’s helpful for all sorts of medical conditions and it guides treatment in the UK amongst doctors. It’s extremely different to what is the guidelines in the American Psychiatric Association, for example, and the difference I suspect between those two things is one of them is done by the UK government. It has very strict rules about conflicts of interest, and you can’t be part of the committee. It’s done. They are charged. NICE is charged with using the public purse for the benefit of the public. And it gives guidance to the NHS. In America, the guidelines for depression are written by the American Psychiatric Association, which is a group that’s trying to forward the interest of psychiatrists, not for psychiatry, for psychiatrists.

There’s no conflict of interest rules. All of the members of these committees generally have conflicts of interest and the drug companies that pay the guideline committee members are always mentioned in the guidelines. It might be a coincidence, but there does seem to be a relationship, and so if you read these two texts, it’s like completely different worlds.

The American Psychiatric Association Guidelines list a series of medications to use. The NICE guidelines, it does include medications, but it actually recommends 19 different treatments for depression that are equally effective and cost effective, including for severe depression. And some of the non-drug treatments include, various forms of therapy, CPT individuals, psychodynamic, mindfulness, exercise.

In fact, the number one most cost-effective treatment for severe depression according to NICE is problem solving therapy, which means you write down your top three problems, the first step you’ll take for each one, and report back with barriers encountered or progress made, which really gets to the idea that problems in our lives is what causes, so much grief.

Now NICE is only, can only write, in relation to what it’s got studies for. And so it doesn’t cover a lot of lifestyle issues. And so it’s unfortunate and I certainly think it does have exercise in it. I certainly think that diet and community, must play a role, access to green spaces.

I hear people have different experiences of the different diets and I think that ketogenic diet, intermittent fasting, I hear positive things from different people. I don’t know if there are studies out there. I think those things have minimal side effects compared to medications and so are worth trying?

Personally, as an n equals one experiment, when I tried keto, I felt much more calm. I don’t, that’s not proof. I don’t know if it worked for everybody. I suspect there might be differences, but I guess, thinking about these things, I always think what’s the benefit and what’s the harm?

And I just say I think harm is more important than benefit. If I had a child that was given a non-beneficial treatment, I wouldn’t be so happy if I wouldn’t mind they were given a harmful treatment, I’d be much more unhappy. So I think safety is more important than efficacy, and that’s why I think things that don’t have serious safety issues.

Unlike antidepressants, we haven’t talked about all the safety issues, but I probably known a bit to your audience. And so I think those lifestyle options are worth trying alongside the other things that I mentioned. 

Bret: 
Yeah. gosh, it’s fascinating to hear about the difference between the NICE guidelines and the APA and the US guidelines and the conflict of interest here in the US is just rampant and the conflict of interest of the authors on this paper too. It’s unusual to find a paper written like this by someone who isn’t getting tons of grants or money or compensation from pharmaceutical companies.

And that’s just accepted, right? That’s just the way it is and we really do need to stand up to that and say, no, let’s get rid of that and make it more like the European guidelines. So that’s fascinating. We could have a whole discussion on that in and of itself, but that was really interesting to hear.

But I really want to thank you for coming on and joining me on the show here to talk about this paper and more importantly, how it fits into the whole sort of the whole environment of antidepressant discontinuation, tapering and trying to different differentiate the symptoms of relapse versus withdrawal.

I think you really add a unique perspective and the key being that this is nothing new. This is not new data and it’s easy to say it’s a meta-analysis of RCTs, therefore it’s the highest quality data. But I think you’ve really pointed out, what you put in the soup really makes the soup, and there definitely is some weaknesses.

I thank you very much. If people want to learn more about you and your work and follow with you, where can we direct them to go? 

Mark: 
I’m on Twitter. I’ve been quite active the last few days. at Mark Horo, M-R-K-H-R-O, I’ve got a dinky website. www.markhorowitz.org. Can I just add, so I don’t want to drag this out, can I just add one safety message to the audience just so I just maybe to summarize the study and then put it in context? I think you’ve said it exactly right, Bret, know this study has shown again that short-term use antidepressants most doesn’t cause severe withdrawal. And I think that’s true.

There are 25 million people in America on these drugs more than two years. There are millions people around the world on these drugs more than two years. All the studies suggest that long-term users are at much higher risk for severe, long lasting and sometimes disabling withdrawal syndromes. That’s what I’m concerned about.

To some degree this study might be interpreted to say everyone might should use these drugs for age to 12 weeks because it’s not major issues when they stop. Now, that wouldn’t be a bad takeaway from this study, but if you are a longer term user, i’d be much more careful in coming off.

The guidelines in America suggest to come off over a few weeks. That can be quite dangerous for a lot of people. It’s better to come off more slowly. That means months, sometimes more than a year. There’s a method of tapering called hyperlink tapering that I’ve done a lot of work on that involves smaller reductions that is generally safer.

I should say I run a clinic called Outro. In America, it’s operating in various states, including New York and California, that helps people to come off these drugs more safely. But even a doctor can follow these things with the latest guidelines. I’ve written a book called The Maudsley Deprescribing Guidelines that outlines how to come off a lot of different psychiatric drugs including antidepressants.

And so I guess I hope that doctors and patients are not, unjustifiably, become complacent about withdrawal because of this study. I think short term people, yes, be complacent. That seems more reasonable. Not everyone, but most people, but longer term users, it’s better to err on the side of caution when things go wrong.

It’s very un, it’s very unpretty. Better to be cautious than to become reckless. 

Bret: 
Very good that’s a very important message. So thank you very much. I appreciate that. 

Mark: 
Thanks, Bret. 

Bret: 
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