There is no clear evidence that depression is caused by low levels of serotonin, researchers said when questioning the widespread use of antidepressants.
The new review of existing studies found the condition is unlikely to be caused by a chemical imbalance and said people should be made aware of other options for treating depression.
However, other experts, including the Royal College of Psychiatrists (RCP), urged people not to stop their medication in light of the results, arguing that antidepressants were effective.
NHS figures show the number of people in England taking antidepressants continues to rise. In 2021/22, 8.3 million patients received antidepressants, a 6% increase over the previous year when the number was 7.9 million.
Overall, an estimated 83.4 million antidepressant prescriptions were prescribed in 2021/22, a 5% increase from the previous year.
In the new study, researchers from University College London (UCL) said 85% to 90% of the public believe depression is caused by low levels of serotonin, or a chemical imbalance.
Most antidepressants are selective serotonin reuptake inhibitors (SSRIs) and were originally intended to work by correcting abnormally low levels of serotonin.
Lead author Joanna Moncrieff, Professor of Psychiatry at UCL, is a Consultant Psychiatrist at the North East London NHS Foundation Trust (NELFT).
She said: “It’s always difficult to prove a negative, but I think we can say with certainty that after a large amount of research that has been done over several decades, there is no convincing evidence that depression is caused by Serotonin abnormalities are caused, specifically by lower levels or reduced activity of serotonin.
“The popularity of the ‘chemical imbalance’ theory of depression has coincided with a tremendous increase in antidepressant use…
“Thousands of people suffer from the side effects of antidepressants, including the severe withdrawal symptoms that can occur when people try to stop taking them, yet prescription rates continue to rise.
“We believe this situation is partly due to the mistaken belief that depression is due to a chemical imbalance.
“It is high time the public was informed that this belief is not based on scientific knowledge.”
The review looked at studies involving tens of thousands of people examining serotonin and depression.
One of the findings was that research comparing levels of serotonin and its breakdown products in the blood or brain fluid found no difference between people diagnosed with depression and healthy people.
The authors also reviewed studies in which serotonin levels were artificially lowered in hundreds of people and concluded that lowering serotonin levels in this way did not induce depression in hundreds of healthy volunteers.
Other studies looked at the impact of stressful life events and found that the more stressful life events a person had experienced, the more likely they were to be depressed, showing the important impact of external events.
According to the study, there is also evidence from other studies that antidepressants can cause low serotonin levels in the long term.
Prof Moncrieff said: “We don’t understand exactly what antidepressants do to the brain, and when we give people this kind of misinformation, it prevents them from making an informed decision about whether or not to take antidepressants.”
A spokesman for the Royal College of Psychiatrists said: “The effectiveness of antidepressants varies in different people and the reasons for this are complex, making it important that patient care is based on the needs of each individual and is regularly reviewed.
“Continued research into treatments for depression is important to help us better understand how drugs work and how effective they are.
“Medicines should be available to anyone who needs them. We would not advise anyone to stop taking their antidepressants based on this review and encourage anyone with concerns about their medication to contact their GP.”
In a 2019 statement on antidepressants, the college said the primary mode of action of most antidepressants is to target monoamine neurotransmitter function, at least initially, by increasing the availability of serotonin or norepinephrine, or both.
It added: “The original idea that antidepressants ‘correct a chemical imbalance in the brain’ is an oversimplification, but they do have early physiological effects and impact on some aspects of psychological function.
“They can induce changes in the function of brain areas that are associated with improvement in depressive symptoms.”
Professor Allan Young, director of the Center for Mood Disorders at the Institute of Psychiatry, said of the new study: “The (undiscussed) elephant in the room is good evidence of the efficacy and acceptability of serotonergic antidepressants.
“The use of these drugs is based on clinical study results that inform their use for patients.