After decades of study, there remains no clear evidence that serotonin levels or serotonin activity are responsible for depression, according to a major review of prior research led by UCL scientists.

The new umbrella review — an overview of existing meta-analyses and systematic reviews — published in Molecular Psychiatry, suggests that depression is not likely caused by a chemical imbalance,and calls into question what antidepressants do. Most antidepressants are selective serotonin reuptake inhibitors (SSRIs), which were originally said to work by correcting abnormally low serotonin levels. There is no other accepted pharmacological mechanism by which antidepressants affect the symptoms of depression.

Lead author Professor Joanna Moncrieff, a Professor of Psychiatry at UCL and a consultant psychiatrist at North East London NHS Foundation Trust (NELFT), said: “It is always difficult to prove a negative, but 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.

“The popularity of the ‘chemical imbalance’ theory of depression has coincided with a huge increase in the use of antidepressants. Prescriptions for antidepressants have risen dramatically since the 1990s, with one in six adults in England and 2% of teenagers now being prescribed an antidepressant in a given year.

“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.”

The umbrella review aimed to capture all relevant studies that have been published in the most important fields of research on serotonin and depression. The studies included in the review involved tens of thousands of participants.

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