New research shows the theory justifying antidepressants is just a myth

SSRIs and other antidepressants are no better than a placebo for mild to moderate depression

Depression being a chemical imbalance has been proven to be unfounded

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Like millions of patients who seek help from their GPs for depression, Emma Ward was repeatedly told she was suffering from ‘an imbalance of chemicals in the brain’.

If Emma wanted to get better, her doctors said the 26-year-old should keep taking the antidepressants she had been prescribed since she was 15 — even though the drugs did not seem to improve her mood, and left her feeling perpetually numb emotionally.

Now, shocking new research published yesterday shows that the theory justifying the millions of prescriptions for antidepressants handed out every month to patients such as Emma, is simply not true.

The research confirms what some medical professionals have increasingly come to suspect. That the ‘chemical imbalance’ theory — that depression is due to a lack of the brain chemical serotonin — is nothing more than a myth.

This myth was created more than 35 years ago by pharmaceutical companies to justify their products, and has been perpetuated ever since by the training and practice of doctors around the world. In the most comprehensive review of the research on links between depression and serotonin ever carried out, researchers from the UK, Italy and Switzerland looked at 17 major international reviews that had documented the findings from more than 260 studies, involving 300,000 patients.

Their findings, published in the journal Molecular Psychiatry, undermine the basis for decades of prescribing of the most commonly used antidepressants, Selective Serotonin Reuptake Inhibitors, or SSRIs.

‘For years, people have been led to believe that depression is caused by a chemical imbalance in the brain, due to a deficiency of the chemical serotonin,’ the lead researcher, Professor Joanna Moncrieff, a professor of psychiatry at University College London and a consultant psychiatrist at North East London NHS Foundation Trust, told the Mail.

‘We can safely say that after a vast amount of research conducted over several decades, there is no convincing evidence that depression is caused by serotonin abnormalities.’

Serotonin is a neurotransmitter, a chemical that transmits messages between nerve cells. The NHS website says that while ‘it would be too simplistic to say depression and related mental health conditions are caused by low serotonin levels . . . it is thought SSRIs work by increasing serotonin levels in the brain’.

The findings are a major upset, since SSRIs account for the majority of antidepressants prescribed in the UK, and millions of Britons rely on them.

Their use is rising inexorably — of the record 7.4 million antidepressant prescriptions issued in England in March alone, almost four million were SSRIs. The majority of patients prescribed antidepressants are women.

There are currently eight different SSRIs prescribed in the UK, among them fluoxetine, the mother of all SSRIs — better known as Prozac.

Fluoxetine was developed by U.S. pharmaceutical giant Eli Lilly in the early 1970s, based on ‘the hypothesis’ that boosting serotonin would help treat depression, and it soon became apparent that the company had struck gold.

According to a 2005 paper, by two of Fluoxetine’s inventors, ‘revenue from antidepressant sales was valued at less than $200 million in the first eight months of 1975’.

Prozac was approved for the treatment of depression in the U.S. in 1987, and by 2002 it had been prescribed to more than 40 million patients worldwide, with total sales of $22 billion.

‘Part of the reason why the story of chemical imbalances in depression has become so prevalent is because it was propagated by drug companies when they were marketing new antidepressants,’ says Dr Mark Horowitz, a co-author of the new study.

‘Antidepressants have been blockbuster drugs for the pharmaceutical industry, frequently ranking among their most profitable.’

Yet in recent years, the ‘chemical imbalance’ theory has been increasingly questioned. In a position statement on antidepressants in 2019 the Royal College of Psychiatrists said ‘the original idea that antidepressants “correct a chemical imbalance in the brain” is an oversimplification’.

But the theory is still taught at medical schools and in psychiatric textbooks. In its guidance on treating depression in adults, NICE says SSRIs ‘modify neuronal transmission in the brain’ — in other words, they work on serotonin levels.

Just a few weeks ago, during an interview on BBC Radio 4’s Woman’s Hour, Dr Nighat Arif, resident GP on both ITV’s This Morning programme and BBC Breakfast, was asked why she thought more women than men were being put on antidepressants.

Women, she said, were not only more likely to ask for help, but also ‘understand that there is a chemical imbalance and antidepressants given at the right time will help with that imbalance’.

And yet ‘it has been suspected for some years that the evidence for this “brain imbalance” doesn’t stack up,’ says Professor Moncrieff. ‘But no one has got the evidence together and really looked at it properly.

‘However, now we have and it confirms that there is no convincing evidence that serotonin is linked with depression, and certainly not that low serotonin is a cause of depression.

‘We suggest it is time to acknowledge that the serotonin theory is not empirically substantiated.’

If the drugs don’t work by tackling a mythical ‘imbalance’, this could explain previous research which has found that SSRIs and other antidepressants are no better than a placebo for mild to moderate depression.

Certainly, according to the new review, antidepressants ‘work’ mainly because people believe they do. The researchers write: ‘It is often assumed that the effects of antidepressants demonstrate that depression must be at least partially caused by a brain-based chemical abnormality, and that the apparent efficacy of SSRIs shows serotonin is implicated.

‘Other explanations for the effects of antidepressants have been put forward, including the idea they work via an amplified placebo effect.’

Even if antidepressants do have a placebo effect, they are active drugs that can have unpleasant side-effects, including loss of libido and emotional numbness. Some people can also struggle to come off them because of severe withdrawal symptoms.

Take Emma Ward — she’s an NHS psychologist, which makes the way she was treated all the more incredible. We’ve changed her name to protect her identity at her request.

Several times over the years, Emma had tried to wean herself off the various antidepressants she was put on as a teenager, but she was always defeated by the side-effects of withdrawal: ‘it felt like my brain was submerged in water in a really choppy sea’.

Then, two months ago, desperate for help to come off the antidepressant fluoxetine, she spoke to her Community Mental Health Team, only to be told ‘bizarrely, and infuriatingly, I was just being “resistant to getting better” ’.

By this stage, she’d done her own research and questioned the chemical imbalance theory — ‘but I was told not believing in it was an indication of paranoid thoughts, because the theory was “scientifically proven”. On that basis, they recommended I should start taking anti-psychotics’.

Stevie Lewis, 66, a former business consultant was prescribed antidepressants after being told she had developed a chemical imbalance.

Now a campaigner against the overuse of antidepressants and a board member of the International Institute for Psychiatric Drug Withdrawal, Stevie was on an SSRI for 17 years, most of which she spent ‘trying and failing to stop’ because the withdrawal effects were so severe.

‘I am outraged that I and so many other people have been persuaded to take a drug based on unproven science,’ says Stevie, from Catbrook, Monmouthshire.

Women are more likely to be paying the price for the medical profession’s adherence to the myth of chemical imbalance, for the simple reason that more women than men are prescribed antidepressants.

A survey by the Women’s Nutritional Advisory Service in 2019 found that 40 per cent of women experiencing perimenopause were prescribed antidepressants to help manage their (hormonal) symptoms. A study this year found women were more than twice as likely to be diagnosed with anxiety and prescribed antidepressants. Professor Martin Marshall, chair of the Royal College of GPs (RCGP), said this was because women are ‘more comfortable seeking help for mental health conditions’ than men.

Stevie Lewis was first prescribed antidepressants in 1996, when she was 41, and began suffering intermittent insomnia and unexplained anxiety once a month.

‘I now know I was going through the classic perimenopause, but it wasn’t discussed in those days. Instead, I was told I was on the edge of a nervous breakdown, that I had a chemical imbalance in my brain and that these tablets would correct it.

‘What astonishes me is that doctors, who are supposed to be scientists, have perpetuated this story for the best part of 30 years. It is shameful.’

Shown the new research by Good Health, Dr Arif said that like legions of doctors before her, she’d been taught ‘that depression is caused by low serotonin’.

She added: ‘If newer research is correcting this long-held belief, then I welcome the discussion and will look again at how I communicate how antidepressants work with my patients.’

Lead researcher behind the new review, Dr Horowitz, a training psychiatrist and clinical research fellow in psychiatry at University College London, said that during his training he, too, was taught depression was caused by low serotonin — ‘I even taught this to students in my own lectures’.

Now, he says, ‘it feels like everything I thought I knew has been flipped upside down’.

Professor Moncrieff says: ‘We do not understand what antidepressants are doing to the brain, and giving people misinformation prevents them from making an informed decision about whether to take them or not.’

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