To use analogies to make it simple.

I sort of think about, you know, a heavy rock sinking into wet mud.

You know, it sinks more and more, you know, 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, I mean, that's a general law, you know, of pharmacology, of drugs that affect the brain, drugs that cause withdrawal.

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

Welcome to the Metabolic Mind Podcast.

I'm your host, Dr. Brett Scher.

Metabolic Mind is a non profit initiative of Bouzouki 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.

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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?

Well, what is that risk?

Well, a new paper was just published suggesting that that risk is very small, that the risk of discontinuing antidepressants is extremely mild and not even really clinically significant.

But is that true?

Well, 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 Outroclinic 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 has a very different.

A 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 if 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.

Good to see you again too, Brett.

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.

Right.

Well, I guess I'm on sort of both sides of the desk on this.

I started my training as a psychiatrist in Australia and the UK.

I did a PhD in how antidepressants work at 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 20s and I was given Lexapro Arrest Telepram.

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 or 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.

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 majority of the teacher.

I got a very, 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.

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 is 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.

Is an uncomfortable feeling.

It's uncomfortable for you, I'm sure, like you said, you're sort of on both sides of the equation as a learning and practicing psychiatrist, but then experiencing this.

So I guess one big question is, and it could be a long question, but 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.

So it took me a while to work out what the disconnect was.

You're right.

And so 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.

So I spent like, you know, any doctor spends 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 for 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 8 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, people given sertraline, Zoloft and especially Venlafaxine or Effexor 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 8 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 America and around the uk.

And because there was a dozen such studies, when guideline committees came to rights, 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 think it's fairly innocent.

They only saw studies that showed mild and brief symptoms.

And so they were reflecting what the 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 more withdrawal effects you get when you stop it.

I mean, 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're 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 to use analogies to make it simple.

I sort of 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.

And that makes a lot of sense.

And then so applying that to this paper, I mean, in a way I guess you could say it's more of the same.

But so the paper is called Incidence and 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 help you 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, but as you pointed out on social Media, in 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 and 11, if you could.

Right, 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 a sort of control, or continued an antidepressant.

So they're trying to isolate what's just due to the drug and what's due.

You know, there's obviously psychological factors that might play 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 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 the.

That was what.

And they said, well, the threshold is normally 4 symptoms, 1.08 is less than 4.

And so this is not a significant withdrawal syndrome.

And that was the main.

You know, 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 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 8 to 26 weeks.

10 of them went for 8 to 12 weeks.

So these actually, these are, I sort of talked at the beginning, guidelines are based on these 8 to 12 week studies.

Some of the studies included were those original 8 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 bit of a 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 Valdoxin.

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 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 had people on antidepressants for eight to 12 weeks before they stopped.

So it's exactly history of repeating.

We're back to the original studies done by drug companies that the analysis is based, that they base their analysis on.

Yeah, and that gets kind of 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 you know, if you look at the debates on social media, you know, you say, look, this is the meta analysis of randomized controlled trials.

This is sort of the pinnacle of research quality as opposed to saying, you know, you've pointed out that you have survey data, right.

And 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, the question is, what are we missing?

Like 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?

Yeah, so there's a few points to make there.

Number one, I agree it is frustrating to see old data repackaged because, you know, this is exactly 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 8 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 going to find the issues which are of course what happens to long term people on long term use of antidepressants.

It's not true.

So 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, 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 randomize autistic 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 des, this scale that is focused on in the CALFAS meta analysis and it showed huge levels of withdrawal.

The average number of death symptoms coming off paroxetine was 8, coming off sertraline, Zoloft was 5.

The proportion of people that had a withdrawal syndrome was 60% for Zoloft and 66% for Paxil.

And that's, you know, I don't know why they didn't include that Rosenbaum study in their analysis, but it clearly shows incredibly high levels of withdrawal in longer term users.

So those are not surveys, those are randomised 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.

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Well, 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.

So, I mean, that's really important.

But I guess another question is why is it so important?

And part of the reason is, you know, determining withdrawal from a recurrence of the depression that required the treatment, which is so important.

And of course, you know, I've been trying to read all the conflicting views, but one is, well, 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 from the medication and what is a recurrence recurrence of their initial symptomatology of depression?

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 where they looked at individual symptoms, one of them is depressed mood.

They've 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, so 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 kind of contact the researcher 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, it 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 match that.

Depression scores didn't go up at all or 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 shot 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 in clinical practice.

And that's kind of 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, determine what the symptoms are because one would be, well, 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?

Right, 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 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 20s being confused or whatever, it is already a little bit, it 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, they were coming off their antidepressants and six weeks later they developed brain zaps and headache and dizziness.

I thought that is very strange.

You know, 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, 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 Ockins razor.

If you have a runny 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, 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, but you feel terrible.

And we've seen in study after study that anxiety, low mood, suicidality are common symptoms of withdrawal, because you can see them even in people who would 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 if they say I was lethargic, I was sleeping all the time, I was really depressed, and I said, what did you have when you came off the drugs?

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 stopped 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 yeah, those are the main ways of telling.

Yeah, that's a good point.

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 maybe just, you know, the majority of the people who are started on an antidepressant for a reason.

But I think we also have to acknowledge there is this subset of people who are 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, maybe, yeah, maybe those.

People are more prone to relapse.

You know, 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 2 points on a 52 point depression scale compared to placebo.

There's all sorts of ways of the way they do those.

Those studies inflates the effect of antidepressants.

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 say if you stop an 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.

That's not what drugs do.

Drugs wear off over time.

They don't get more effective over time.

That's the opposite.

And so 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 asked that Rosenbaum study, 30% of people of 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, do 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.

So I think that there is scant evidence that antidepressants prevent relapse in the long term from existing studies.

Yeah.

And I guess really the overarching theme here that we also should address is, are antidepressants sort of 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 will 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?

So, again, just step back for a second.

You know, I think this is one that we've.

We've reified depression in our culture, which means we talk about it like it's a thing, you know, like heart disease or asthma.

But we know sort of.

I sort of go back to simple things that my grandmother would have said.

You know, when life is awful, we feel bad.

So, you know, that makes us understand what's going on, you know, so if we're feeling bad because our relationships are unsatisfying or full of conflict, if our work is unsatisfying, if we have financial problems, well, 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.

So 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 are dissatisfied with their life or unsatisfied with their lives or overwhelmed by their lives, or don't have their emotional needs met?

You've 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.

Well, 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.

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 interests of psychiatrists.

It's not for psychiatry, it's 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, individual 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 that'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 with 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.

You know, personally, as an N equals one experiment.

When I, when I tried keto I felt much more calm.

You know, I don't, that's not it, that's not proof.

I don't know if it'll work for everybody.

I suspect there might be differences, but I guess, you know, thinking about these things I always think what's the benefit and what's the harm?

And I would say I think harm is more important than benefit.

You know, if I had a child that was given a non beneficial treatment, I wouldn't be so happy, but I wouldn't mind if they were Given a harmful treatment, I'd be much more unhappy.

So I think, you know, safety is more important than efficacy.

And that's why I think things that don't have serious safety issues, you know, unlike antidepressants, which we haven't talked about all the safety issues, but I probably, probably known a bit to your audience and so I think those lifestyle options are worth, worth trying alongside the other things that I mentioned.

Yeah.

Gosh, it's fascinating to hear about the difference between the NICE guidelines and the APA and the US Guidelines.

And I mean, the conflict of interest here in the US is just rampant.

And the conflict of interest of the authors on this paper too.

I mean, it's unusual to find a paper written like this by someone who isn't getting tons of grants or Medicare or money or compensation from pharmaceutical companies.

And that's just accepted, right?

That's just sort of 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 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 weakness.

So thank you very much.

If people want to kind of learn more about you and your work and follow with you, where can we direct them to go?

So I'm on Twitter, I've been quite active the last few days at Markhorro M I 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 just maybe to summarize the study and then put in context.

I think you've said it exactly right, Brett.

Now, this study has shown again that short term use of antidepressants mostly doesn't cause severe withdrawal and I think that's true.

There are 25 million people in America on these drugs for more than two years.

There are millions of people around the world on these drugs for 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 should use these drugs for 8 to 12 weeks because they're 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 hyperlock 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 Altro in America that'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 Morsely 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 unpretty.

Better to be cautious than to become reckless.

Very good.

That's a very important message.

So thank you very much.

I appreciate that.

Thanks Brian.

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