No convincing evidence that depression is caused by low serotonin levels

A comprehensive review of existing meta-analyses and systematic reviews has found that there is no convincing evidence that depression is caused by serotonin abnormalities, particularly by lower levels or reduced activity of serotonin.

The new research calls into question what antidepressants do, since most work by correctly chemical imbalances or abnormally low levels of serotonin in the brain.

This is concerning given that there has been a huge increase in the use of antidepressants 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,” says lead author of the study Professor Joanna Moncrieff, a Professor of Psychiatry at UCL and a consultant psychiatrist at North East London NHS Foundation Trust (NELFT).

“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,” she concludes.

The umbrella review included tens of thousands of participants

The review, which included tens of thousands of participants, analysed all relevant studies that have been published in the most important fields of research on serotonin and depression.

It found that, when comparing serotonin levels and its breakdown in the blood or brain fluids, there was no difference between people diagnosed with depression and the control group.

Other studies have artificially lowered serotonin levels in hundreds of people by depriving their diets of the amino acids required to make serotonin. One of the studies, a meta-analysis conducted in 2007, found that lowering serotonin in this way did not produce depression in hundreds of healthy volunteers. There was very weak evidence in a small subgroup of people with a family history of depression, but this only involved 75 participants, and more recent evidence was inconclusive.

The researchers also looked at very large studies which considered the role of gene variation, including the role of the gene transporter. They found no difference in these genes between people with depression and healthy controls. Instead, stressful life events were much more likely to cause depression – the more stressful life events a person had experienced, the more likely they were to be depressed.

Anyone considering withdrawing from antidepressants should seek the advice of a health professional

The researchers say their findings are important as studies show that as many as 85-90% of the public believes that depression is caused by low serotonin or a chemical imbalance.

While the study did not review the efficacy of antidepressants, the authors encourage further research and advice into treatments that might focus instead on managing stressful or traumatic events in people’s lives, such as with psychotherapy, alongside other practices such as exercise or mindfulness, or addressing underlying contributors such as poverty, stress and loneliness.

Professor Moncrieff adds thousands of people suffer from the side effects of antidepressants, including the severe withdrawal effects that can occur when people try to stop them. He therefore says it is ‘high time’ to inform the public that the chemical imbalance theory is not grounded in science.

However, the researchers caution that anyone considering withdrawing from antidepressants should seek the advice of a health professional, given the risk of adverse effects following withdrawal. As Dr Michael Bloomfield, a consultant psychiatrist and principal clinical research fellow at UCL explains: “Many of us know that taking paracetamol can be helpful for headaches, and I don’t think anyone believes that headaches are caused by not enough paracetamol in the brain. The same logic applies to depression and medicines used to treat depression.

“There is consistent evidence that antidepressant medicines can be helpful in the treatment of depression and can be life-saving.”