Depression ‘not a brain chemical imbalance’

Scientists admit having no idea how antidepressants work after study shows no link to serotonin levels

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 is prescribed antidepressants, most of which act by maintaining serotonin levels, the analysis suggests depression is not actually caused by low serotonin. Depression may be more strongly equated with negative life events that lower mood, the review found.

DEPRESSION is not a chemical imbalance in the brain, and scientists have no idea how antidepressants work, a major review by University College London (UCL) has concluded.

Although one in six adults in England is currently prescribed antidepressants, most of which act by maintaining serotonin levels, the analysis suggests depression is not actually caused by low levels of serotonin.

Depression may be more strongly equated with negative life events that lower mood, the review found.

Since the 1990s, antidepressant use has grown with the theory that the drugs establish correct levels of chemicals in the brain – but researchers say that theory is unfounded.

Joanna Moncrieff, the lead author and professor of psychiatry at UCL, said: “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.

“Many people take antidepressants because they have been led to believe their depression has a biochemical cause, but this new research suggests this belief is not grounded in evidence.”

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.

Researchers looked again at studies into levels of serotonin and depression and found no difference between thousands of people diagnosed with depression and healthy control participants.

They also analysed studies where serotonin levels were artificially lowered in hundreds of people and found that it did not make them depressed. People with variations in the gene governing the transportation of serotonin also had no difference in depression levels.

However, stressful life events exerted a strong effect on the risk of becoming depressed – the more stressful events a person experienced, the more likely they were to be depressed.

The team said studies show 85 to 90 per cent of the public thinks depression is caused by low serotonin or a chemical imbalance. There is also evidence that believing that low mood is caused by an imbalance provokes pessimism around managing moods without medical help.

Dr Mark Horowitz, a co-author, 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... everything I thought I knew has been flipped upside down.”

Researchers said patients should not be told depression is caused by a chemical

‘Being involved in this research was eye-opening ... everything I thought I knew was flipped upside down’

imbalance or that SSRIS solve the problem. Although antidepressants can work, they must be doing so through a different route, the paper concludes.

Experts warned against ditching medication. A Royal College of Psychiatrists spokesman 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.”

Prof Allan Young, director of 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 ... This review does not change that.”

The review was published in the journal Molecular Psychiatry.