It’s the social media hashtag adorning everything from pictures of sunsets to girls’ nights out: ‘serotonin moments’, a phrase now synonymous with happiness.
Serotonin, of course, is one of the neurotransmitters (chemical messengers) that carry messages between nerve cells in the brain. This hyper-focus on serotonin reflects how deeply embedded it is in our society that a serotonin imbalance or deficiency is what causes depression.
Indeed, all mental health problems – as they’re now referred to – are overwhelmingly seen as medical conditions arising from a chemical imbalance, or something similar, which needs correcting with drugs just like other diseases.
In the case of depression, the prescription is likely to be for antidepressants, including selective serotonin reuptake inhibitors (SSRIs) – Prozac is the most famous – which claim to ‘fix’ levels of serotonin.
So widely believed is this idea of antidepressants being a chemical ‘fix’ for an ‘imbalance’ that you can now also buy antidepressant-themed paraphernalia joking about their widespread use: T-shirts, keyrings and bags carry slogans such as ‘If you’re happy and you know it, thank your meds’ and ‘Today’s good mood is sponsored by antidepressants’.
But what if I told you this idea of a chemical imbalance is a myth?
The fact is the theory that depression is caused by low serotonin is not supported by reliable evidence. Put simply, the emperor has no clothes – and this matters, because our widespread use of antidepressants for mental health problems is grounded in this myth.
Senior NHS psychiatrist Professor Joanna Moncrieff said she’s been vilified for showing that medicating misery by doling out antidepressants is based on a myth
Data shows that 8.6 million people in England were taking an antidepressant in 2022-23 – almost 19 per cent of adults. Increasing numbers also use anti-depressants long-term, often for years. More than half of those taking antidepressants in England have been taking them for at least a year – and these are mainly SSRIs.
Having been a senior NHS psychiatrist for more than 20 years, alongside conducting research and academic work, I’ve witnessed how the myth that antidepressants normalise an underlying brain dysfunction has facilitated the successful promotion of highly profitable drugs – drugs whose harmful effects were never properly investigated.
At the same time, the quest for money and professional status has lured the psychiatric profession (whether individuals are consciously aware of it or not) into promoting these barely useful and potentially harmful drugs.
And the hubris of the scientific community has also made it unwilling to consider challenges to its worldview, however well evidenced those challenges are.
People have been profoundly misled about antidepressants.
Not only have they never been shown to rectify a chemical imbalance or any other abnormality, but – as I shall explain – they actually interfere with the normal state of the brain, just like alcohol and other mind-altering drugs. This is how they can produce potentially devastating side-effects – from rare suicidal thoughts to severe sexual problems.
My view on depression is that it’s a complex emotional state usually arising from life difficulties, rather than a biologically determined condition. I have no problem if people choose to take antidepressants. And, of course, they should only stop taking them under medical guidance.
But I also want people to be properly informed about what they take. This was my aim in 2022 when I published a comprehensive overview of research into depression and serotonin in the journal Molecular Psychiatry.
It showed that, despite decades of heavily funded investigations, there was no convincing evidence that depression is caused by an abnormality in serotonin.
This review is now one of the most widely read and influential scientific papers of modern times, ranked by Altmetric, an online influence tracker, in the top five per cent of all papers.
People are reading this paper because they are stunned to find that the link between depression and serotonin is not backed up by evidence. The view of depression as a brain disorder is seen as the unalterable truth.
Serotonin is a chemical found in various parts of the body – most is located in the gut and in blood cells known as platelets. Only around 8 per cent is in the brain.
One academic from Oxford University said ‘it would be surprising if such a widely distributed brain neuromodulatory system [i.e. serotonin] was completely uninvolved in the complex experiences that make up clinical depression’.
But this is the equivalent of saying blood is involved in depression because it’s also ‘widely distributed’ all over the brain.
In fact, there have been hundreds, if not thousands, of studies attempting to identify how brain chemicals affect emotions, intelligence and behaviour. They have shown little evidence of any links.
While my team and I weren’t the first to suggest the serotonin depression theory was unproven, no one was aware quite how weak the evidence was. For example, because you can’t stick needles into people’s brains, it’s generally agreed that the most direct measure we have of serotonin in the brain is the concentration of the main breakdown product of serotonin known as 5-HIAA – a molecule in the cerebrospinal fluid surrounding the brain, which can be analysed via a lumbar puncture.
We identified 19 studies that looked at this. Overall, they found no difference in the level of this molecule when comparing people with and without depression.
Surprisingly, our review also found research suggesting long-term antidepressant use may reduce serotonin levels.
Three studies involving a total of 2,469 post-menopausal women showed that those who were using antidepressants for any condition, such as depression, pain or anxiety, had lower serotonin levels than those not taking antidepressants. So despite the theory that SSRIs boost serotonin, this was evidence that they may reduce serotonin, at least when used for a sustained period.
You wouldn’t know any of this from reports regularly describing how serotonin produces ‘a sense of wellbeing and happiness’ – nor from members of the psychiatric profession who reacted to our paper with disdain and panic, which truly shocked me.
Although I’ve been challenging the mainstream story about antidepressants for decades, the publication of the serotonin paper meant I could no longer be ignored by the psychiatric establishment.
It went into attack mode and tried to neutralise our findings and divert attention from their implications for our use of antidepressants, in order to avoid public debate.
It deluged the academic literature and the public with a host of other unconvincing studies and alternative theories, dressed up with complex language and technical details.
The UK’s Science Media Centre coordinated the initial response to our paper. Its mission is to improve the public understanding of science – a laudable aim – but it receives funding from numerous pharmaceutical companies as well as the industry’s trade association, the Association of the British Pharmaceutical Industry. Its spokesmen on mental health regularly include advocates of drug treatment and biological interventions.
Ironically, the Science Media Centre had originally been approached by my university, University College London, to collaborate on publicising the paper, as it does for other important research.
But it then withdrew that offer and released a briefing featuring seven psychiatrists criticising the paper. A spokesman for the Royal College of Psychiatrists was also quoted, reassuring people about antidepressants.
Subsequently a group of 36 psychiatrists submitted a response to Molecular Psychiatry, the journal that had published our paper. They disputed minor points of methodology and claimed there was some evidence for the role of serotonin in depression. They continued to attempt to discredit the paper, both online and to anyone who would listen.
Her study suggests there was no convincing evidence that depression is caused by an abnormality in serotonin
The medical press, reluctant to cover our original research, seemed delighted to report this criticism.
I was even reliably informed by an attendee that cheers went up at the British Association for Psychopharmacology conference in 2023 when the questioning of our review was mentioned.
It seems that our findings had become a cause celebre in some professional circles.
I shouldn’t have been surprised. After all, the serotonin thesis has been kept alive because the pharmaceutical industry has long recognised that medicating misery is a lucrative market.
Indeed, SSRIs were marketed in the 1990s to step in for drugs such as Valium. The scandal of the mass prescription of highly addictive drugs such as Valium brought the idea of using medication to numb emotions into disrepute.
So a new narrative was needed if drugs were still to be marketed for psychological problems.
The ‘chemical imbalance’ was that narrative, enabling SSRIs to be presented as the opposite of emotional anaesthetics.
Instead they were said to be sophisticated medical agents targeting an underlying ‘disease’ – the disease of depression. How could people resist this sort of message, especially when it was delivered not just by drug firms, but by their own doctors?
Surely, though, you must be thinking, SSRIs were tested by drug companies for effectiveness before being launched on the public? Yes and no.
First, measuring depression isn’t simple – it’s not like taking blood pressure. The scales that are used don’t entirely make sense. One scale, for example, rates you as depressed if you spontaneously say you are, rather than if you only admit it after being questioned.
And we can’t be confident that someone who scores 20 points on a depression scale is more depressed than someone who scores ten, and it certainly makes no sense to say they’re twice as depressed.
Furthermore, clinical trials show antidepressants are not much better than a placebo pill. In fact the difference is so small, it’s unlikely to have any real impact on people’s lives.
Then there’s the problem that this small effect is probably not a real effect of antidepressants at all. I was first alerted to this when I was a junior psychiatrist wondering why my colleagues thought antidepressants were so effective, which was different from my experience. I asked a more senior doctor what he thought.
He said antidepressants were ‘active’ placebos, and referred me to a 1982 paper in the British Journal of Psychiatry. Reading it was a lightbulb moment.
The paper, by a psychiatrist called Richard Thomson, pointed out that because antidepressants are active drugs, with recognisable side-effects such as drowsiness, sexual dysfunction and emotional blunting, it’s likely some people in trials will figure out if they’re taking antidepressants or the placebo. Researchers may also be able to guess who’s taking what.
We know that a person’s mood is strongly affected by whether they think they’re getting the real active drug – therefore if they can guess that they got the antidepressant, this will improve their mood. Conversely, those who suspect they’re on the placebo may feel disappointed, making their mood worse.
Researchers might also rate people they suspect to be taking the real drug as doing better. So the effects of the drug may actually be due to what’s known as an ‘amplified’ placebo effect. This is a combination of the ordinary placebo effect – the psychological benefit of taking a tablet – amplified by the boost people derive from side effects, because it suggests they’re getting the real drug, and they respond to that.
When I later updated Thomson’s review it confirmed that there’s little, if any, difference between antidepressants and an active placebo. Despite this, psychiatrists continue to insist that ‘antidepressants work’ – and that it doesn’t matter if we don’t understand why.
Prescribing drugs has also long fulfilled the ambitions of the psychiatric profession to be just like other doctors – bringing them ‘out of the asylum’ by administering pills to make patients better.
The introduction of SSRIs and other drugs in the late 1980s made psychiatrists an important industry target. They became accustomed to drug company inducements.
In the early 1990s, I saw drug company paraphernalia everywhere. Doctors wrote with drug company pens on drug company sticky notes; tea was served in drug company mugs.
At least once a week a lavish lunch would be provided, courtesy of one firm or another. This would be followed by a promotional talk, dressed up as education, provided by the drug company representative or a senior psychiatrist in the company’s pay. Conferences took place at expensive hotels. ‘Key opinion leaders’ among the profession were paid generously for giving presentations about a firm’s product.
The money massaged the profession’s vulnerable ego. Antidepressants brought psychiatrists the kudos they craved.
This is not meant to impugn anyone’s motives. The drug industry does develop useful products. Working with it to bring genuine therapeutic innovations is not inherently wrong.
But pharmaceutical companies are ultimately interested in profit. And the potential side effects of SSRIs are significant.
Known to prolong bleeding time, they have been linked to haemorrhages, birth complications and strokes. Evidence suggests they reduce bone mineral density, causing osteoporosis and fractures. In younger people, antidepressants can cause agitation and impulsivity (and, though it is rare, suicidal behaviour).
Severe withdrawal reactions are also associated with them, and these sometimes last for years.
Another potentially devastating and sometimes long-term complication is sexual dysfunction. Antidepressants can reduce sexual desire; delay and minimise orgasm intensity; and cause erectile problems and delayed ejaculation.
No one should be prescribed antidepressants without being warned about these effects in the strongest possible terms, yet the medical community has not been quick to publicise them.
When I see patients who want to start antidepressants, I explain that they have these harmful effects and that they also cause emotional blunting, which may reduce the intensity of their feelings.
I also add that there is minimal evidence that they are helpful. I encourage people to try other measures to improve their mood – first by addressing the problems that are making them low or anxious, and second through engaging in things such as exercise or mindfulness.
The reality is psychiatric drugs such as antidepressants affect us in the same sort of way as alcohol or recreational drugs.
They, too, can ‘drown our sorrows’, or at least suppress them. But far from correcting an underlying chemical imbalance or abnormality, psychiatric drugs change our normal brain chemistry.
As the serotonin thesis continues to tarnish, its champions are showing signs of wanting to persuade us that depression is instead something to do with other biological abnormalities – perhaps nerve cell connections. Yet these new ideas aren’t supported by convincing evidence either.
An array of substances linked to recreational drugs are being promoted for depression, including ketamine and psychedelics. They’re claimed to counteract an underlying biological abnormality or deficiency – often by people with links to firms marketing them.
The message remains the same – depression is in the brain and drugs can fix it.
The pharmaceutical industry and its allies need business to go on as usual. That way, the market will be sustained and people won’t pause to think about the fact that they’re taking foreign chemicals into their bodies – chemicals we understand little about and which are unlikely to be harmless, especially if taken day in, day out, for years on end.
- Chemically Imbalanced: The Making And Unmaking Of The Serotonin Myth by Joanna Moncrieff is published on Thursday (Flint, £20).
