The Myth of Low-Serotonin & Antidepressants - Dr. Mark Horowitz

[Music] Welcome to another episode of After School. My name is Mark Horowitz. I'm a training psychiatrist and researcher, and today I'm going to be talking about common misconceptions that people have about depression and antidepressants. Without further ado, here we go.

go there are a number of myths about depression and anti-depressants that are hard to dislodge most notable is the myth that depression is caused by a chemical imbalance in the brain if you ask people in Western countries about 80

There are a number of myths about depression and antidepressants that are hard to dislodge. Most notable is the myth that depression is caused by a chemical imbalance in the brain. If you ask people in Western countries, about 80 to 90% of them will say they believe this to be true.

proposed by academics but was propagated widely by drug companies as part of their marketing push for anti-depressants that pre serotonin in the short term The Selective serotonin reuptake Inhibitors or ssris that are so familiar to us today these drugs became

The chemical imbalance theory is the colloquial description of the hypothesis that depression is caused by low serotonin, a chemical transmitter in the brain. This idea was first proposed by academics but was propagated widely by drug companies as part of their marketing push for antidepressants that increase serotonin in the short term. The selective serotonin reuptake inhibitors, or SSRIs, that are so familiar to us today, these drugs became blockbusters and one of the most widely used classes of drugs in the world.

anti-depressants they can often experience low mood anxiety and a host of other symptoms they can often conclude or are told by doctors that they are experiencing a return of their underlying condition and therefore need to stay on these drugs sometimes for

Most people still don't know that there is no evidence that depression is caused by low serotonin, and researchers no longer think this is true. When people stop antidepressants, they can often experience low mood, anxiety, and a host of other symptoms. They can often conclude or are told by doctors that they are experiencing a return of their underlying condition and therefore need to stay on these drugs, sometimes for life.

that they need to come off them more carefully and slowly there has been new re research in this field on hyperbolic tapering a specific way of slowly reducing their dose and an advance over oldfashioned ways of tapering that can

However, we now know that withdrawal symptoms from these drugs can look very similar to anxiety and depression and can be easily mistaken for them. So these symptoms are not a sign that people need to stay on the drug but may indicate that they need to come off them more carefully and slowly.

them for taking them that's the last thing I want to do because aside from being a psychiatric researcher and training psychiatrist I myself have used antidepressants for 20 years although I am now stopping them so I am in the same

There has been new research in this field on hyperbolic tapering, a specific way of slowly reducing their dose and an advance over old-fashioned ways of tapering that can help people to come off more safely. Before I talk much more about these ideas, I just want to say that many people feel that they have been helped by antidepressants, and I in no way want to take that away from them or shame them for taking them.

prescribing anti-depressants in the past anti-depressants were reserved for severe conditions going back about 25 years ago when they were given to about three in 100 people since then rates of prescribing have been increasing every year in Western countries and this trend

That's the last thing I want to do because aside from being a psychiatric researcher and training psychiatrist, I myself have used antidepressants for 20 years, although I am now stopping them, so I am in the same boat as lots of other people. My major aim is that people are more informed about what these drugs can and can't do.

have been on the medication for more than 5 years rates are similar Across the Western World with about 1 in six to 1 in8 adults using anti-depressants in any given year in Europe the UK and Australia we also know from studies that

One of the most common ways of treating mental health conditions like anxiety and depression has become prescribing antidepressants. In the past, antidepressants were reserved for severe conditions, going back about 25 years ago when they were given to about three in 100 people. Since then, rates of prescribing have been increasing every year in Western countries, and this trend only increased more sharply in America, especially during the pandemic.

drugs the role that medication plays in depression and anxiety is contested in academic circles there are two main ways of thinking about what psychiatric drugs do and this is from the work of J Moncrief a professor of Psychiatry

Across the world, there are at least 100 million people on antidepressants. According to the CDC, over 43 million Americans are on an antidepressant, which is about one in four adults. Over 15 million Americans have been on the medication for more than five years. Rates are similar across the Western world, with about one in six to one in eight adults using antidepressants in any given year in Europe, the UK, and Australia.

underlying cause of the infection relieving the symptoms of cough and cold and for a long time drugs like anti-depressants have been marketed in just the same way that in some way anti-depressants are reversing the process of depression like antibiotics

We also know from studies that a lot of these drugs are prescribed to people who don't have approved indications for taking the medication. That is, between a third and a half of people on antidepressants currently have or never had an evidence-based reason to be on the drugs.

academic psychiatrists but it was only in the 1990s and 2000s that the idea became widely spread to the public through advertising by drug companies a famous commercial showed a sad blob with low serotonin in its head that was made

The role that medication plays in depression and anxiety is contested in academic circles. There are two main ways of thinking about what psychiatric drugs do, and this is from the work of J. Moncrieff, a professor of psychiatry working in the public health system in Britain.

on social media talking about low serotonin days the media has wholeheartedly embraced this explanation for depression of course if you believe that depression is caused by low serotonin then it seems perfectly sensible to take a drug that increases

One has been called the disease-centered model, which is borrowed from mainstream medicine. A good example would be antibiotics for a bacterial lung infection. The antibiotics target and kill the bacteria and so solve the underlying cause of the infection, relieving the symptoms of cough and cold.

well because it makes their products seem natural sensible and safe however it turns out that this entire explanation was mostly a marketing line the hypothesis put put forward by psychiatrist 50 years ago has not been borne out by subsequent

For a long time, drugs like antidepressants have been marketed in just the same way, that in some way antidepressants are reversing the process of depression like antibiotics kill bacteria. This way of thinking about antidepressants was tied into the story that most people believe about depression, that it is caused by a chemical imbalance or low serotonin.

you look in cerebros spinal fluids blood scam people's brains or look at their brains after they have died or look at their serotonin genes or even deprive them of Serotonin by changing their diet there is no evidence linking low

This idea was first conceived of as an academic hypothesis in the 1960s by academic psychiatrists, but it was only in the 1990s and 2000s that the idea became widely spread to the public through advertising by drug companies. A famous commercial showed a sad blob with low serotonin in its head that was made happy again when Zoloft was given to it and raised its serotonin levels.

low serotonin then anti-depressants can't be reversing this underlying chemical cause of of depression they can't be said to be acting in the same way as antibiotics there's now a whole range of other theories about what anti-depressants might do acting on

Drug companies have been incredibly effective at communicating this idea to the point it has entered popular discourse and taken on a life of its own, with people on social media talking about low serotonin days. The media has wholeheartedly embraced this explanation for depression.

of thinking about what psychiatric drugs do particularly anti-depressants and that is what Professor monrie calls the drug centered model an example would be we know that alcohol is very effective for social anxiety if you drink alcohol it will make you feel calm it reduces

Of course, if you believe that depression is caused by low serotonin, then it seems perfectly sensible to take a drug that increases serotonin, as the SSRIs do in the short term. Just as if someone with diabetes was told they lacked enough insulin in their body, of course, they would be happy to take insulin.

disorder is caused by an alcohol deficiency we know that alcohol is a drug that acts on the brain and causes certain changes to our emotions and thoughts that are superimposed on top of Whatever anxiety you have underneath and

So this explanation has served the objectives of these companies well because it makes their products seem natural, sensible, and safe. However, it turns out that this entire explanation was mostly a marketing line. The hypothesis put forward by psychiatrists 50 years ago has not been borne out by subsequent research.

if we look at them through this lens there are a wide variety of different compounds that are called anti-depressants and they have differing effects some of them are a bit energizing some are a bit sedating many of them cause emotional numbing that's

Most psychiatrists now say that they had long ago given up this idea and that no informed psychiatrist would say such a thing. We recently published a large study looking at all the evidence linking serotonin and depression. Whether you look in cerebrospinal fluids, blood scans, people's brains, or look at their brains after they have died, or look at their serotonin genes, or even deprive them of serotonin by changing their diet, there is no evidence linking low serotonin level or activity with depression.

healthy volunteers without any depression they cause blunting of emotions this emotional numbing has also been linked to the genital numbing often experienced by people on anti-depressants in fact if you crush up many anti-depressants and swish them around your mouth with some water they

Our paper dispelling this myth was widely covered in the media because this was news to most of the public who had been led to believe this. So if there's no convincing evidence that depression is caused by low serotonin, then antidepressants can't be reversing this underlying chemical cause of depression. They can't be said to be acting in the same way as antibiotics.

those symptoms but anti-depressants are not so targeted as just to affect negative emotions they affect all emotions including ones we enjoy so there might be unforeseen consequences of such an approach in the long term numbing might affect relationships

There's now a whole range of other theories about what antidepressants might do, acting on inflammation, causing the growth of new neurons, etc. None of them proven in humans; most derive from work in animals. So if there's no proof that they fix an underlying chemical problem, then what could they be doing?

been hundreds of studies conducted comparing anti-depressants to Sugar pills over about 8 weeks and in these studies everybody gets better over 8 weeks whether they're given an anti-depressant or a sugar pill we know that depression tends to get better over

There's another way of thinking about what psychiatric drugs do, particularly antidepressants, and that is what Professor Moncrieff calls the drug-centered model. An example would be we know that alcohol is very effective for social anxiety. If you drink alcohol, it will make you feel calm. It reduces anxiety. It will make you feel more at ease in social situations, whether you have a social anxiety disorder or not.

depression also people tend to work through their problems they get over the Lost job or relationship move on in some way and that is called natural recovery people also respond to the hope of being given a treatment and that is what the

We don't think that alcohol is reversing the underlying cause of social anxiety disorder or that social anxiety disorder is caused by an alcohol deficiency. We know that alcohol is a drug that acts on the brain and causes certain changes to our emotions and thoughts that are superimposed on top of whatever anxiety you have underneath.

points on a 52 point scale between the two one large study found that it takes a six to seven point difference on this scale to cause noticeable Improvement so that many people think that the difference between anti-depressants and

And when the drug wears off, the anxiety will come back. Some people have suggested that this may be a more appropriate way to think about what psychiatric drugs are doing. So what do antidepressants actually do to...

are evaluating their own products people will know they're on an anti-depressant in these studies because of the side effects dry mouth nausea Etc and we know that this can lead to expectations of improvement what is called the Amplified

placebo effect which can make people in the drug group do better and these studies are done very short term depression can last for long periods months or years and the vast majority of these studies go for 6 to 12 weeks the

duration of these studies is a far cry from how long the drugs are taken in the real world with nearly half of American adults who are on anti-depressants taking them for more than 5 years moreover drugs tend to wear off over

time and so differences from Placebo tend to become smaller this is true for benidipine drugs like Valium and opioid drugs like oxy Consin which look effective at 6 weeks but their effects wear off over time what works to start

with is erased by the process of Tolerance we know this also occurs for anti-press presence because they give you withdrawal effects when you stop them the flip side of Tolerance Americans refer to this colorfully as anti-depressant poop out in the few

studies that have gone for long periods of time like a study from the American government called the STD study after 12 months of treatment with anti-depressants only 5% of people were free of depression and had not dropped out of the study so we really don't have

very good evidence that these drugs are useful in the long term we know lots of people think about coming off their anti-depressants some of the most common reasons people give is the numbing effects that people experience or other side effects also

called adverse effects like sexual problems weight gain daytime tiredness trouble with memory and concentration other people are more concerned about the long-term physical health risks which can include increased risk of osteoporosis heart disease Strokes Falls and even an early death

others feel that whatever was causing stress in their life has passed or they have developed other ways of coping and they would like to try coming off their drugs the first thing to say to anyone considering stopping anti-depressants is

they should absolutely not stop these drugs cold turkey this can be a dangerous thing to do to some people we know now that there are withdrawal symptoms from anti-depressants and that for some people these can be severe can

last for long periods and can sometimes be life-threatening like lots of drugs taken long term being on anti-depressants causes physical dependence that's different from addiction these terms are often confused addiction involves people who are craving a drug they become fixated some

people break the law to get more of the drug that of course doesn't happen with anti-depressants but you don't need that to become physically dependent on a drug for example probably most people myself included are physically dependent on

caffeine we're not craving it not thinking about it all day we're not stealing from our neighbors to get it but if we stop caffeine we'll get withdrawal symptoms and similarly anti-depressants cause physical dependence and when you stop them you're

at risk of getting withdrawal symptoms this occurs simply because the body has become accustomed to a certain level of the drug and misses it when it's reduced as anti-depressants affect almost every system in the body the brain the gut the

hormonal system the muscular system the effects of stopping them are very wide ranging so there's physical symptoms like dizziness perhaps the most common symptom brain fog difficulty concentrating and remembering things headache unsteadiness on your feet people also have a strange sensation

that things around them are not real they become dreamlike called depersonalization and derealization some people have these very particular electric shocks in their head which they describe as either their brain being shut off for a second or a

little zap in their heads sometimes on moving their eyes people can get muscle Tremors or spasms they can have nightmares doctors are often poorly informed about these withdrawal symptoms which means the diagnosis is often missed the the second category of

withdrawal symptoms are probably the ones that cause the most confusion and trouble and that is emotional withdrawal symptoms this is not to say that these are symptoms in someone's head these are physiological symptoms of withdrawal that are expressed through emotions

because of course anti-depressants affect the brain they affect the way we think and feel and so some very common withdrawal symptoms are depressed mood anxiety panic attacks crying fear trouble sleeping some people can become very agitated when coming off

anti-depressants we know that these symptoms are symptoms of withdrawal and not just a return of an underlying condition because even people who have no underlying condition experience them when they stop for example people who have put on antidepressant for pain or

the menopause can experience for the first time in their lives some of these emotion withdrawal symptoms on stopping of course we all know all sorts of drugs that cause emotional withdrawal symptoms on stopping like caffeine nicotine amongst others if you don't know what to look

for then these emotional symptoms of withdrawal can look a lot like the underlying condition that people were first given the anti-depressants for like anxiety or depression this can confuse a lot of people so doctors can jump to the conclusion that this must be

a relapse that is a return of an underlying condition rather than withdrawal symptoms if someone walks into a doctor's office and says they've stopped their anti-depressant they can't sleep and they feel awful it is very likely that the diagnosis of relapse

will be made on the spot by the doctor this leads to people being put back on anti-depressants and sometimes told that they need the drugs perhaps even lifelong this is very unfortunate because a more sensible approach to withdrawal symptoms would be to conclude

that the person just needs to come off the drug in a more careful way not that they need to stay on it we have learned over the last few years from large studies that withdrawal symptoms from anti-depressants are much more common

can be more severe and longer lasting than official guidance has said for many years if you look at these studies about half of patients will experience withdrawal effect when they stop their drugs in surveys of patients about half

of those with withdrawal symptoms will say the symptoms are severe so perhaps one in four people will have severe symptoms when they stop anti-depressants because there are so many people on these drugs that is a lot of people these symptoms which drug

companies used to say would only last a week or two we now know can last for months and in some people for more than a year and sometimes even longer at the moment knowledge on how to safely stop

anti-depressants is a major blind spot in psychiatric and medical education there is much greater attention paid to starting these drugs than stopping them so on the one hand there have been a thousand studies on starting anti-depressants there's only been about

a dozen on stopping them mostly because this hasn't been in the interest of the major funer of these studies the drug companies that make the drugs and it is these studies that inform what is then taught in medical schools and ends up in

guidelines so what do we know about stopping anti-depressants the worst possible way to stop anti-depressants is to stop them in one day i. you throw them in the bin your brain has gotten used to a certain level of effect from

the drugs and going to zero straight away is the neurobiological equivalent of jumping from the top of the 10th story of a building and the consequence es can sometimes be very unpleasant what makes more sense is coming down floor by floor so that your

body and brain have time to readjust to lower levels of the drug this will cause less of a jolt to your system even better is to come down step by step so that the worst that could happen is you

bang your knees a little and that is what gradually tapering off a drug is all about but at the moment the most common approach to stopping anti-depressants by most prescribers is to half the dose for a couple of weeks

and then to half the dose again for another couple of weeks Often by giving a tablet on every second day and then stop for some people that seems to be okay but for a large proportion of people they can get terrible withdrawal

symptoms from this approach their doctors mostly diagnose relapse and patients often get put back on the drugs some of them end up going elsewhere like social media or P of support sites for advice on how to stop their drugs as

they lose faith in their doctors there's a reason for this misalignment in clinical practice and patient experience in the late 1990s drug companies worked with some academics to minimize the risk posed to their product by knowledge of withdrawal they coined the term

discontinuation symptoms a euphemism for withdrawal symptoms that makes them sound benign they arranged the writing and printing of several academic articles that describe them as brief and mild and they sent these articles out to doctors in America and Europe and that

became the Mantra stopping anti-depressants you get a few discontinuation symptoms and they're brief and Mild that was what the guideline said for many years in England and it is what it still says in North America today and if that is what's in

your mind as a doctor then there's no big deal in stopping these drugs so if you stop them and you do have trouble and you turn up to your doctor with severe symptoms that are longlasting the doctor thinks it can't be withdrawal

effects because after all these are mild and brief it must be the underlying condition coming back and that becomes the medical education that Junior doctors are exposed to this misunderstanding has helped fuel the widespread prescribing and long-term continuation of these

drugs but there has been some green shoots recently some healthc Care Professionals have caught onto What patients have had to figure out on their own a better way of coming off these drugs in the last few years there has been a technique called

hyperbolic tapering that has become better known this is a science-based approach to tapering anti-depressants built on an understanding of the relationship between the dose of the drug and its effect on the brain that is blocking their main target the ser T and

transporter and also the other receptor targets put simply very tiny doses of anti-depressants have outsized effects on the brain when there is not much drug in the brain every extra milligram has a large effect but when you get to the

larger doses that are often used in clinical practice every extra milligram has less and less additive effect because most of the receptors are already occupied by the drug this leads to a patent called a hyperbola to describe the relationship between the

dose of drug and the effect on the brain the relationship is very steep at low Doses and flattens out at higher doses an example of the LW of diminishing returns this relationship can help us to understand why people get into so much

trouble coming off anti-depressants in the way most doctors recommends the usual approach is called linear tapering and it involves reducing by the same amount of medication each time for example 5 mg so you might go from 20 mg

to 15 mg to 10 mg to 5 mg to nothing the first reduction does not cause much change at all in terms of effects on receptors each subsequent change will have a larger and larger effect on the brain because of the hyperbolic shape of

the curve so when you go down from 5 milligrams to 0 milligrams it sounds like the same size reduction in terms of dose as going from 20 Mig to 15 Mig 5 Mig but actually it can have almost 20

times as large an effect on the brain as going from 20 milligram to 15 mg because the changes are so steep at lower doses this exactly matches What patients report that reducing their dose at the beginning is not too difficult but when

they get down to lower doses it becomes harder and harder to make reductions and doctors are mostly unaware of this relationship and so often conclude that because people have trouble at the end they must need the medication imagine walking down a flight

of stairs in the dark but the final steps are several meters high rather than just a few centimeters this is the Trap the traditional approaches to tapering these drugs have missed and people conclude that those stairs are just too dangerous to walk down

hyperbolic tapering takes into account the shape of this curve you make smaller and smaller reductions as you get down to lower doses so that each step causes the same sized effect on the brain like carefully climbing down a steep Cliff

rather than jumping off of it there needs to be a fundamental shift in the way in which we understand what causes mental health challenges the main thing that people should understand is that research points to the fact that

that depression and anxiety largely arises from the things we experience in life those stresses like job loss relationship breakdown illness not from faulty biology in fact studies show that by the age of 40 86% of people will experience clinical levels of depression

or anxiety so this is a common part of the human experience it's from this perspective understanding the specific problems and challenges that an individual faces rather than lumping everyone in the same bucket of chemical problems that we can best understand

what might help each person best manage their problems studies show that if people understand their mental health problems in terms of what is going on in their lives they feel more hopeful for the future more empowered to help themselves

and less likely to use medications on the other hand people who are told that they have a chemical in their brain that only medications can fix what has sometimes been referred to as the broken brain explanation feel more hopeless less able to help

themselves and of course more willing to take medication a fact that can hardly be lost on the marketing departments that ran these campaigns at a societal level the main drivers of mental health problems are poverty job insecurity relationship

conflict and loneliness physical illnesses and other things that threaten people's basic emotional and physical needs so perhaps rather than there being a renewed call for more research into genetics and brain Imaging every time there is a tragic suicide or a celebrity

comes forward with their tale of mental health problems what we need to do is to address the social drivers of Despair and hopelessness in some ways trying to change the brain to fix these problems is like opening up the back of a

computer to solder the circuit board when a piece of software crashes on an individual level people can take steps to manage and improve their own mental well-being through practices like mindfulness exercise nurturing relationships getting better sleep and learning about nutrition small changes

to our habits can produce large results and finally I'm not saying that medication plays no role in managing mental health problems but that we should be better informed about what medication can and can't do thanks for listening to another

episode of after school I hope what you heard was informative if you want to learn more about my work or about Jonah Mon's work or learn more about how we're helping people in Canada and the US to safely stop anti-depressants with outro

you can check the links in the description otherwise stay safe and have a good day