Closeup of man getting ready to take a pill with water

Despite decades of study, there is no evidence that serotonin is responsible for depression, raising questions about a basis for the widespread use of antidepressant drugs, say the authors of a new review of published research.

Depression in recent decades has been thought to be caused by a chemical imbalance, including levels or activity of the neurotransmitter serotonin. The popularity of this “serotonin hypothesis of depression” has coincided with a steady increase in the use of antidepressants since the 1990s, the authors said.

The drugs are frequently prescribed in nursing homes, for example, where antidepressant use has been estimated to range from 35% to 60%. 

The new review, published in the journal Molecular Psychiatry, may upend this theory, said lead author Joanna Moncrieff, MD, of University College London.

“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,” she said in a statement.

Moncrieff does not recommend telling patients depression is caused by low serotonin or by a chemical imbalance, or that antidepressants work by targeting these problems. 

“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,” she and her colleagues concluded.

Antidepressants can cause side effects and some may cause withdrawal symptoms when stopped, Moncrieff added. The authors recommended that withdrawal from antidepressants should be done under supervision of a clinician.

The review aimed to examine all relevant studies published in key fields of research on serotonin and depression and involved tens of thousands of participants overall.

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