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Depression not caused by ‘chemical imbalance’, say researchers

Depression not caused by ‘chemical imbalance’, say researchers

Patients should not be told that depression is a chemical imbalance in the brain, say researchers who found ‘no convincing evidence’ that depression is caused by serotonin abnormalities.

The team at University College London (UCL) said many patients who take antidepressants had been led to believe that their depression may have a biochemical cause, however the evidence for that is lacking.

Although antidepressants can work for patients, it is not clear how they work, they said and patients needed to be aware of that when making decisions about treatment.

Several experts commenting on the study, which has caused a fair bit of debate, said the findings of the research were not new and most psychiatrists would adhere to a biopsychosocial model of depression rather than a simplistic theory.

The new umbrella review examined existing meta-analyses and systematic reviews of serotonin and depression and found difference in levels between people diagnosed with depression and healthy controls

In studies where serotonin levels were artificially lowered, there was no link with depression and people with variations in the gene regulating serotonin transportation also showed no difference in levels of depression, they reported in Molecular Psychiatry.

But stressful life effects have been shown to have a strong effect on people’s risk of becoming depressed, they concluded.

Final NICE guidance on depression published last month advocated a wider choice of treatments and a move away from antidepressants in people whose condition is ‘less severe’.

Study lead Professor Joanna Moncrieff, a professor of psychiatry at UCL and a consultant psychiatrist at North East London NHS Foundation Trust, said there was ‘no convincing evidence that depression is caused by serotonin abnormalities, particularly by lower levels or reduced activity of serotonin’.

She added that popularity of the ‘chemical imbalance’ theory of depression coincided with a huge increase in the use of antidepressants with one in six adults in England and 2% of teenagers now being prescribed an antidepressant in a given year.

Professor Moncrieff said: ‘Our view is that patients should not be told that depression is caused by low serotonin or by a chemical imbalance, and they should not be led to believe that antidepressants work by targeting these unproven abnormalities.

‘We do not understand what antidepressants are doing to the brain exactly, and giving people this sort of misinformation prevents them from making an informed decision about whether to take antidepressants or not.’

Professor David Curtis, honorary professor at the UCL Genetics Institute, said the results presented in the paper were not new.

‘The notion of depression being due to a “chemical imbalance” is outmoded, and the Royal College of Psychiatrists wrote that this was an over-simplification in a position statement published in 2019.’

He added that SSRI antidepressants do not increase serotonin levels but alter the balance between serotonin concentrations inside and outside neurons but their antidepressant effect is likely due to more complex changes in neuronal functioning which occur later as a consequence of this.

‘It is important that people with severe depression are not discouraged from receiving appropriate treatments, which can make a huge difference to them and those around them.’

A spokesperson for the Royal College of Psychiatrists said antidepressants were an effective, NICE-recommended treatment for depression.

‘Treatment options such as medication and talking therapy play an important role in helping many people with depression and can significantly improve people’s lives.

‘Antidepressants will vary in effectiveness for different people, and the reasons for this are complex, which is why it’s important that patient care is based on each individual’s needs and reviewed regularly.’

‘Continued research into treatments for depression is important to help us better understand how medications work as well as their effectiveness.

‘We would not recommend for anyone to stop taking their antidepressants based on this review, and encourage anyone with concerns about their medication to contact their GP.’


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Please note, only GPs are permitted to add comments to articles

Tom Johnson 22 July, 2022 8:03 pm

It’s called placebo. Pure quackery. However to some individuals with a bit of gift-wrapping and spin it makes them believe. And if the pills are yellow they work even better. Now if only people could access the talking therapies properly and within a reasonable timeframe we may be able to reduce antidepressant use. But until that point with 10mins to play with the pills will do. The science is irrelevant.

Reply moderated
Patrufini Duffy 22 July, 2022 10:50 pm

My friend Emily said fluoxetine is better than citalopram, but I like sertraline because mirtazapine gave me mood swings and I went bezerk when I started microgynon, and now I heard escitalopram is really good and you can drink on it and party like there’s no tomorrow. Well that’s what Amy and Darren said at Glastonbury. No I haven’t called a psychologist, I don’t think they’re useful.

Dylan Summers 23 July, 2022 10:12 am

@Tom Johnson

I too suspect that antidepressants are having only a placebo effect for most of our patients. But in a symptomatic condition like depression, is that necessarily a problem? After all, placebos work. And SSRIs are cheap and relatively safe, making them quite suitable for placebo use.

Some" Bloke 23 July, 2022 10:58 am

Don’t need an RCT to know that SSRIs are good at lifting mood among chief execs of pharma companies.
Or maybe that is exactly the wrong attitude, assumptions and prejudice and lack of awareness typical of lazy GP like me. More research is needed! (Research like this is good for lifting mood of researchers and publishers)

Tom Johnson 23 July, 2022 4:37 pm

It certainly is not a problem. It’s why we use them to help that individual in front of us think something or someone is helping them. They then feel better. I’m just cynical about the researchers justifying their existence. Second to last paragraph is an example. I reckon smarties would work as well.

Malcolm Kendrick 25 July, 2022 3:46 pm

Neuropsychopharmacology = vast profits for the pharmaceutical industry. Let put hundreds of millions of people around the world on a class of drugs to treat a chemical inbalanace in the brain that does not exist. You know it makes sense, and we most certainly keep on doing it, because otherwise…. Otherwise….

David jenkins 26 July, 2022 4:24 pm

perhaps these professors would like to volunteer to come and treat a few patients in the real world ?

i wonder how long they would last saying “NO” to everybody !!

Giles Elrlngton 28 July, 2022 11:27 am

“Researchers… found ‘no convincing evidence’ that depression is caused by serotonin abnormalities”.

Absence of evidence is not evidence of absence.