Depression is not a chemical imbalance in the brain and scientists have no idea how antidepressants work, a review by University College London has concluded.
Although one in six adults in England are currently prescribed antidepressants – most of which act by maintaining serotonin levels – the new analysis suggests depression is not actually caused by low levels of serotonin.
Instead, depression may be more strongly equated with negative life events which lower mood, the review found.
Since the 1990s, antidepressant use has grown alongside the theory that the drugs establish correct levels of chemicals in the brain but researchers say that is unfounded.
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“I think 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, particularly by lower levels or reduced activity of serotonin,” said lead author Joanna Moncrieff, a professor of psychiatry at UCL.
“Many people take antidepressants because they have been led to believe their depression has a biochemical cause, but this research suggests this belief is not grounded in evidence.”
Important for mood and sleep
Most antidepressants are selective serotonin re-uptake inhibitors (SSRIs) which prevent the loss of a chemical that carries messages between nerve cells in the brain, and is important for mood and sleep.
For the new review, researchers looked again at studies into serotonin and depression and found no difference in levels between thousands of people diagnosed with the condition and healthy control participants.
The authors also looked at studies where serotonin levels were artificially lowered in hundreds of people by depriving their diets of the amino acid required to make serotonin, and found that it did not make them depressed.
People with variations in the gene governing the transportation of serotonin also showed no difference in depression levels.
In contrast, stressful life events were found to exert a strong effect on people’s risk of becoming depressed – the more stressful life events a person had experienced, the more likely they were to be depressed.
The researchers say their findings are important as studies show that as many as 85 to 90 per cent of the public believes that depression is caused by low serotonin or a chemical imbalance.
There is also evidence that believing that low mood is caused by a chemical imbalance leads people to have a pessimistic outlook on the likelihood of recovery, and the possibility of managing moods without medical help.
Co-author Dr Mark Horowitz, a training psychiatrist and clinical research fellow in psychiatry at UCL said: “I had been taught that depression was caused by low serotonin in my psychiatry training and had even taught this to students in my own lectures.
“Being involved in this research was eye-opening and feels like everything I thought I knew has been flipped upside down.
“One interesting aspect in the studies we examined was how strong an effect adverse life events played in depression, suggesting low mood is a response to people’s lives and cannot be boiled down to a simple chemical equation.”
A different route
The researchers say that patients should not be told depression is caused by a chemical imbalance, or informed that the SSRIs can correct the problem. Although it is clear the antidepressants can work, they must be doing so through a different route, the paper concludes.
Commenting on the research, experts warned people against stopping their medication.
The Royal College of Psychiatrists said: “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. Medication should be available for anyone who needs it.
"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.”
Prof Allan Young, director at the Centre for Affective Disorders at King’s College London, said: “The elephant in the room is the good evidence of the efficacy and acceptability of serotonergic antidepressants.
“The use of these medicines is based on clinical trial evidence which informs their use for patients. This review does not change that.”
The review was published in the journal Molecular Psychiatry.
Depression should not be tackled as if it is a single disorder
Dr Michael Bloomfield, consultant psychiatrist at University College London
Up to one in seven of us will experience depression during our lives. Different people experience different symptoms of depression. While many people experience a mild episode, depression remains a leading global cause of morbidity. Sadly, depression can be potentially life-threatening for some due to an increased risk of suicide. Existing treatments, including several types of antidepressant medicines and psychotherapies (talking therapies), are effective, safe, and not addictive. However, beneficial treatment effects can take weeks to build up and each treatment does not work for everyone. It is therefore essential that we can understand what happens in our brains when we experience depression so that treatments can be improved and targeted.
In the middle of the 20th century, the theory that depression was caused by a chemical imbalance in serotonin represented a really important step forward in the history of medicine. Since then there’s been a huge of amount of research which tells us that the brain’s serotonin system plays very important roles in how our brains process emotions. As depression involves changes in how our brains process emotions, changes in the serotonin system are likely to be important in the development and/or treatment of depression.
The findings from this review are not surprising. Depression has numerous symptom patterns such that two people with depression can have seemingly opposite types of symptoms. For example, some sleep more when they are depressed while others suffer from insomnia. As such, having met scientists and psychiatrists from all over the world, I have yet to meet a colleague who thinks that all cases of depression are caused by a simple “chemical imbalance” in serotonin. Indeed, the serotonin system is complex. What remains likely is that changes in the serotonin system are contributing to certain symptoms in certain people. The challenge with this review is that it isn’t able to address this point because it has grouped together depression as if it is a single disorder which, from a biological perspective, does not make sense.
There is consistent evidence that antidepressant medicines can be helpful in the treatment of depression and even life-saving. This latest paper does not change this. Patients must have access to treatments for depression. Many of us know that taking paracetamol can be helpful for headaches and no one believes that headaches are caused by not enough paracetamol in the brain. The same logic applies to depression and medicines used in its treatment. All medicines can have side-effects and suddenly stopping any treatment can be potentially harmful. Anyone taking a medicine for depression who is thinking of stopping treatment should discuss this with their doctor first.
