From ... in Health — Sep 20, 2022

Taking antidepressants is as risky as taking recreational drugs

Torsten Engelbrecht: Dear Joanna! You say that your recent study, in which you suggest the prevailing hypothesis that depression is caused by decreased serotonin activity or concentration is baseless, “has caused shock waves among the general public“. Why?

Joanna Moncrieff: People believed that there was scientific evidence that demonstrated a link between serotonin and depression. And people have believed that because in the 1990s, the pharmaceutical industry launched a very widespread, heavily funded promotion campaign to persuade people that depression was due to a chemical imbalance and specifically a lack of serotonin, which could be rectified by taking an antidepressant.

That was a huge marketing campaign that was aimed both at doctors, but also at the general public via the internet. And in countries that have direct to consumer advertising, it was directly advertised to consumers on television and radio and other media. And that was very successful.

That campaign was launched in order to counteract people’s underlying common sense feeling that taking a drug for an emotional problem was probably not a good idea.

And that campaign has successfully reversed that idea and replaced it by this belief that depression has been shown to be a chemical problem, which it turns out is not the case. It turns out there is not evidence to support that.

TE: But your criticism actually is not really new. Psychiatrist such as David Healy or Peter Breggin expressed exactly this criticism already years ago. So why does this criticism not reach the surface of reality?

JM: Leading psychiatrists have known for a long time that there was no evidence to support the serotonin theory of depression. But no one has informed the general public of that.

No leading psychiatrists have taken it on board to let the public know.

People like David Healy have, and people like myself and some other people have written about this. The leaders of the psychiatric profession, we have to conclude, have been happy to allow the general public to continue with this misperception that a link between serotonin and depression had been established.

TE: But there’s also contradiction. Ronald W. Pies, for example, professor emeritus of psychiatry counters regarding your review that “historically, psychiatrists have never explained clinical depression solely in terms of reduced serotonin or any specific neurotransmitter“ and as with selective serotonin reuptake inhibitors, so called SSRIs such as Prozac, “many drugs in clinical medicine work through unknown or multiple mechanisms. And this does not affect their safety, efficacy or approval for medical use.”

Doesn’t this contradict your views?

JM: There are a couple of points there that you’ve made. First of all, it is true that psychiatrists have always seen depression as a bio-psycho-social phenomena where the biological is only a part of it.

But there is a problem. If you suggest that there is a specific abnormality in the brain that can be targeted by a drug, then obviously it makes sense to take that drug. Especially if you suggest that other things such as what’s going on in people’s lives are downgraded to a second place and focus on a problem in your brain, then obviously you need to correct it if you can correct it.

But this approach is misleading because to suggest or to tell people that an abnormality had been established, that an abnormality of serotonin had been found has no scientific basis because in fact it hadn’t been found.

You are also right that many psychiatrists have recently been saying that it doesn’t matter how antidepressants work and that these psychiatrists haven’t necessarily been saying that the drugs work by rectifying an underlying chemical imbalance.

There are two points I’d like to say to that. First of all, it really does matter how antidepressants work. And secondly, even if psychiatrists haven’t been promoting the idea of the chemical imbalance, because it has been so widely absorbed and because so many people believe it is established, it’s not good enough to just not promote it.

You actually need to tell people that it is not supported, that there is no evidence for it.

TE: The most important evidence would be a placebo controlled study showing that taking an antidepressant would be much better than doing nothing.

And in this context you say that studies show that antidepressants are only “marginally better than a placebo [or inaction] at reducing depression scores over a few weeks. However, the difference is so small that it is not clear it is even noticeable and there’s evidence that it may be explained by artifacts of the design of the studies rather than the effects of the drugs.“

But I’d like to quote Pies again who counters that “there’s ample evidence from placebo controlled studies that serotonergic antidepressants are safe and effective and the treatment of acute major depressive episodes.“

JM: This is really important. So many people have been saying in response to our paper, that antidepressants work, that they’ve been shown to have important and substantial benefits.

And I would respond to that, that I don’t think that that is true. There have been many large analyses of antidepressant placebo controlled studies that show that the difference between the placebo and the antidepressant is very small. There’s no debate about that.

There’s been a very large study published recently in the journal BMJ. And what it shows is the difference between the antidepressant and the placebo on the depression rating scale score is less than two points on a 52 point scale.

No one thinks that difference is clinically significant. And the other thing is that these trials are all short-term. And as you mentioned, there are lots of other methodological reasons that actually might inflate these differences.

So that small difference may not even be a real difference.

The issue is that if you compare antidepressants with placebos in trials there is a little bit of difference. And the question is what is that difference due to, and I think there are two possible explanations here.

One is that in these trials, people often know whether they’re taking the active drug or the placebo, because they can tell they’re getting a few side effects. They feel a little bit different. And so the people on the active drug in these studies may well be getting what we could call an “amplified placebo effect.“

And that could be the explanation for the difference between the placebo and the drug.

The other possible explanation is that antidepressants have this emotional numbing effect. And so that could be temporarily reducing the intensity of someone’s underlying sadness and feelings of depression, as well as reducing the intensity of any positive feelings that they have, like happiness or joy.

TE: If science is clear that there’s no solid study showing that taking an antidepressant is better than doing nothing or taking a placebo, the why there are people such as Pies still defending the official line?

JM: Psychiatrists appear to be very reluctant to overly criticize antidepressant use. And I think that’s because the psychiatric profession and much of society following their lead has become convinced that depression is a medical problem that can be addressed with a medical solution. And therefore they feel threatened by anything that fundamentally questions that narrative.

TE:: How much influence does the pharmaceutical industry have on psychiatry?

JM: The pharmaceutical industry has been very influential on the public and influential on the psychiatric profession. But we also need to remember that actually the psychiatric profession came up with this idea of the chemical imbalance before this pharmaceutical industry had really got that involved because the theory that depression is related to low serotonin goes back to the 1960s and was proposed by a British psychiatrist.

The pharmaceutical industry really gets into promoting this idea of the chemical imbalance in the 1990s. So they certainly reinforce the idea among the profession of psychiatry, but what they really, really achieve is persuading the public that this is a credible theory that has been established.

TE:: Is there any major study not being financed by the pharmaceutical industry, is there any independent science?

JM: The pharmaceutical industry have massively influenced research on antidepressants because they conduct the vast, vast majority of the studies on antidepressants.

And we know that pharmaceutical industry studies often “inflate“ the effects of the drug that the pharmaceutical company is promoting. If the studies don’t show a positive finding for the company’s drug, they are not being published, they are “buried“.

And even in studies that get to publication often they’ve been tweaked, they’ve been “massaged“, positive outcomes are highlighted more than they reasonably should be.

So, yes, the pharmaceutical industry has definitely had a substantial influence on the research into antidepressants.

TE: I’d like to quote the psychiatrist Pies again who also states that if serotonercic agents are not helpful, antidepressants from other classes may be considered“.

In contrast the US journalsist Robert Whitaker, for example, who is critical of today’s drug fixated psychiatry for many, many years, told me in an interview in 2013 “If you look at how the drug cocktails are prescribed, it’s all really a bit of witchcraft“ in the sense of mumbo jumbo.

So can switching for other medications be a solution – and if so, is there hard evidence that this approach is useful? Or is all this really “witchcraft“ as Whitaker says?

JM: We showed there was no evidence to support the idea that antidepressants might be rectifying an underlying serotonin abnormality.

There is no evidence and there is no better evidence of any other abnormalities of other neurochemicals that might justify the use of antidepressants that work in other ways.

All antidepressants are psychoactive substances in the sense that they change normal mental states. So a lot of antidepressants are reported to, for example, produce a state of emotional numbing, numbing of both positive and negative emotions.

And these are effects that of course are going to impact depression rating scales and other measures that are conducted in randomized trials.

And all antidepressants will affect people, will change people’s normal thinking and feeling in one way or another, or although some of them have very subtle effects.

All sorts of antidepressants do have effects on people, they are not simply „inert“, inactive substances. But we have no evidence that what they are doing is targeting the abnormality that lies underneath depression, or that causes the symptoms of depression, whether it’s a SSRI or another sort of drug.

Many people report that they feel better after taking antidepressants, and many, many people do feel better after taking antidepressants. We know that many people also feel better after taking a placebo.

We know there is no doubt that the majority of the effect of an antidepressant is a placebo effect. The effect of people’s expectations and of being offered hope and support is huge. That has a substantial effect on people’s outcomes.

TE: You also say that “it is not self-evident that manipulating the brain with drugs is the most useful level at which to deal with emotions. This may be something akin to soldering the hard drive to fix a problem with the software.“

It sounds as if you are criticizing the mechanical way of thinking of today’s times that dominates the modern world and to which the French 17th century philosopher René Descartes contributed significantly.

He considered the body of living beings as a kind of a machine. But aren’t the event in the body far too complex to be compared to a computer hard disc that you repair by soldering something? And where does that leave room for dealing with emotions or feelings?

JM: We need our brain and our body as well to think, to feel, to communicate, to do everything that we do. But that doesn’t mean that we can explain the nature of our thoughts and feelings by looking inside the brain.

It’s the wrong level at which to understand human behavior, human thoughts, and human feelings in my view and in the view of many other people who criticize this reductionist view that you can reduce depression or happiness or love or someone’s political views, someone’s taste of books or music to events in the brain.

Many philosophers have written about how this view is nonsensical. These human attributes like love and appreciation of music need to be understood in the context of the human world.

They make no sense if you try and talk about them in terms of nerves and neurological events and activity.

TE:: Even experts such as Pies concede that “there is legitimate debate over the efficacy of long-term anti-depressant use“, while you not only say that it is “impossible to say that taking antidepressant or SSRIs is worthwhile“, but also that “it is not clear that these drugs do more good than harm“. What harm can they do?

JM: This is a really important point. If we have no evidence that antidepressants are working by reversing an underlying abnormality – and we know, and no one denies that, that these are drugs that work on the brain – we have to conclude that these drugs are actually changing the normal state of the brain.

They are modifying it, they are altering our normal brain state, our normal brain chemistry. And if you take a substance that alters your normal brain chemistry every day for weeks and months and years, you may do yourself some harm.

We know that because we know that people who drink a lot every day cause themselves harm and people who take other recreational drugs that also change brain chemistry can do themselves harm.

And we know that taking antidepressants in the long-term can cause a number of harms that relate to the way they modify the brain.

For example, we know now that people become physically dependent on antidepressants and therefore when they try and stop them, they can experience really sometimes quite severe and debilitating and prolonged withdrawal symptoms.

We also know that antidepressants cause sexual dysfunction. They do that even in the short term. And it’s a very common side effect, very well recognized. But it’s becoming increasingly clear that in some people the sexual side effects persist when people stop taking the antidepressant.

And that implies that the antidepressant has changed the brain in some way, in some harmful way.

I’m not saying that this is necessarily a permanent state. We haven’t recognized this effect for long enough, really to know whether it is persistent or permanent or whether it might go away with time. But it’s definitely something that seems to happen to some people who have been using these drugs for long periods of time.

TE: Antidepressants have also been linked by experts such as Peter Breggin as a cause of violent acts and even homicides. What do you think about that?

JM: The evidence suggests that antidepressants can cause younger people to engage in suicidal behavior, more often than people on a placebo. This is evidence from randomized controllled trials.

There is also a higher risk of aggression in young people taking antidepressants compared to young people in these studies who are taking a placebo. The risk in these studies is very small and it’s only in younger people.

The risk is small partly because these studies are trying to select people who don’t have any preexisting risk factors or have a minimum number of preexisting risk factors.

So in real life, the risk actually might be a bit higher. I think that this risk is related to the fact that antidepressants seem to have an agitating effect in younger people in particular. And we don’t know why this happens more in young people than older people, but it does seem to.

So in younger people antidepressants can make someone more agitated, tense, irritable, and emotionally labile. And that effect seems to be related to impulsive behavior which might include self-harming, suicidal and aggressive behavior on occasions.

TE:You also say that “only a minority of medical drugs target the ultimate underlying cause of a disease.” So what would a treatment for mental illnesses like depression look like that addresses these „underlying causes of a disease“?

JM: Medical drugs may not treat the underlying cause of the disease. Most of them don’t, but they do target the underlying pathways, underlying biological pathways that produce symptoms. So even painkillers, which are clearly only a symptomatic treatment, target the underlying neurological mechanisms that produce pain.

Psychiatric drugs work differently. They’re not targeting any underlying processes. They are producing alterations to normal mental states, which are then superimposed onto whatever emotional problem the person is experiencing.

At the moment we don’t know and we have not identified any underlying neurological processes for any sort of mental disorder that could be targeted by a biological treatment. And I’m not sure that we will be able to do because I think that that the view of mental disorders is inappropriately reductionist.

I think that is the view that is trying to find the problem in the brain, rather than looking at the problem at the level of the human being and the human being in her world.

TE: What does this mean for the use of drugs? As I mean, does Peter Breggin, for example, triy to avoid using antidepressants in general. What about you?

JM: If people are feeling depressed and they take a drug, I think you need to see it in the same way as taking alcohol. It changes your mental state temporarily while you were taking it, and then you stop taking it. And the mental state comes back.

And if you’ve been taking the drug for a long time, possibly you get some other complications as well.

So in general, I think that drugs should be avoided and particularly avoided over the long term.
I think there are some crisis situations where a drug such as Benzodiazepine which relaxes people, helps people get to sleep, can be helpful for a few days.

The most important thing for me is to really give people information so that they can make up their own minds about the use of drugs.

And there may be some people who feel that they want to try and change their normal mental state and they want to feel different and they want to numb their emotions.

And then we need to have a debate about whether we think that’s an appropriate medical treatment for emotional problems, whether that’s something that we should be facilitating or not.

But the first thing to do is to be really honest about what is happening when people are taking drugs to deal with their emotional problems and to involve patients in that debate.

TE:What is the alternative then? It’s doing psychotherapy for example, or what about things like sports and nutrition and toxins such as heavy metals?

The book Nutrition and Psyche, for example, whose first edition is from the 1980s, deals with the influence of nutrition, but also of industrial toxins on psychological wellbeing.

And in 2021 the study“Diet, exercise, lifestyle, and mental distress among young and mature men and women” concluded that “our results support the need to customize dietary and lifestyle recommendations to improve mental wellbeing“. Is that an approach you think that should be supported?

JM: So the first thing I would say is that I think we need an approach that starts to see mental health problems differently. So instead of seeing them as diagnoses or disorders that are the same in everyone who has them, we see people as individuals who have their individual set of problems. And every person with depression is responding to a different set of circumstances.

And it’s understanding why someone is depressed and what the circumstances are that have made them depressed. That is the most important thing in helping someone. So each person with depression needs a different solution, depending on what has made them depressed.

If you are depressed because you are having relationship problems, you may need some relationship counseling, you may need a dating app. You may just need a friend to have a cup of tea with and to cry with now.

Again, you know, it’s going to be different for everyone.

That’s the first thing: Everyone has mental health problems for different reasons. And it’s the reasons why people are having these problems that we need to focus on rather than giving people blanket treatments.

Having said that there are some sensible things that people can do to improve them emotional and mental resilience. And one of those is definitely exercise. Exercise has very good effects on mood and on reducing anxiety.

So I think exercise is really important for people. The same holds for eating well, eating a good balanced diet, and just looking after yourself. Making sure that you have enough sleep is another really, really crucial factor for general mental wellbeing.

I think all those things are important. I’m not sure that I want to go down the root of any particular diets or dietary supplements or anything like that. But I think certainly that looking after yourself, doing lots of exercise is definitely going to be helpful.

TE:What should people affected do then? Are there even many therapists who would not drive a drug fixated approach and would be at least willing to abandon on a patient’s request or do let’s say 99.9% of the psychiatrists follow the drug fixated pathway?

JM: Most people are prescribed antidepressants by their general practitioner rather than by a psychiatrist. And I know that general practitioners are trying to offer people alternatives.

So I think that we need a combination of a public information campaign to inform people that this idea of the chemical imbalance was wrong, was not supported and that we don’t know that antidepressants are working in this way and they could be doing something quite different, which has some worrying implications.

And we need to educate doctors, we need to encourage and support doctors to offer patients alternatives to medication such as subscriptions for the local gym.

In the UK, we do have a certain amount of „social prescribing“ whereby doctors can give people gym prescriptions or recommend other social activities for people instead of giving them and prescribing them medication. And we need to support and promote that.

TE:What made you becoming critical – and is it difficult to be critical in your profession or do you get a lot of support as well?

JM: I developed a critical attitude towards psychiatry and traditional medical solutions to psychological problems when I was a trainee, because although other people seem to feel that psychiatric medications like antidepressants worked I really couldn’t see that.

Yes, some people got better, some people got worse. But when people got better, there seemed to be another explanation. It didn’t necessarily seem to be tied to the drug in my view.

So I wasn’t convinced. I developed an interest in psychiatric drugs and started looking at the literature in detail. And then it became obvious that there were lots of methodological and conceptual problems in the research on psychiatric drugs and psychiatric disorders.

I was also aware that some of my fellow psychiatrists shared my concerns about the dominant biomedical approach to mental health problems.

And for that reason, I set up a little group called the Critical Psychiatry Network, which is still going and which consists of psychiatrists like me who have a skepticism towards the biomedical model and a skepticism of the dominance of the pharmaceutical industry and the dominance of medication centered approaches for mental health problem.

TE: What about the whole profession you’re working in, how does it react to your views? Are you only a small group, are you the exception?

JM: We are a minority group and probably most of the leading figures of the profession are people who have an interest in biological psychiatry and have been doing biological research and worked with the pharmaceutical industry. But there are some social psychiatrists who are more focused on the social causes of mental illness and also on social treatments and service configurations. And certainly there are lots of social psychiatrists in the United Kingdom…

TE: …But you’re not under attack or under pressure from, from colleagues or whatever?

JM: There are social psychiatrists and there are people like me, but there is still a great deal of defensiveness, I would say, in the psychiatric profession, particularly when you start to question the basis of drugs like antidepressants that are so widely used.

So yes, I’ve been criticized for speaking out about this paper and for trying to highlight, particularly for trying to highlight the implications that it has, that this research on serotonin has for our understanding of the use of antidepressants.

I do feel that the profession would rather that this subject is not debated in public and would rather that people are not aware of the fact that antidepressants are mind changing and brain changing drugs that may have harmful effects if they’re taken for long periods of time.

TE: Let’s have a quick look into the future: Are you confident that this is gonna be changed or what do you think?

JM: Oh, Gosh! I think there are many people now, especially when I speak to people in the USA, who are utterly convinced that mental health problems are problems in the brain and that we just need to treat the brain and we need to find the right drug or the right sort of biological intervention. That attitude has taken very deep root in the public consciousness in the last few decades. So I don’t see that changing overnight. On the other hand, there are also significant numbers of people who are starting to question that idea. And I think and I hope that those numbers will increase after the publication of our paper and due to debates, like the one that we are having now and that you’ve had with other psychiatrists, other critical psychiatrists and critical voices in the mental health field.

TE: Thank you Joanna for this conversation. I wish you all the best. And thank to all the viewers for watching us. Hope to see you next time again.

JM: Thank you, Torsten

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