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The antidepressant drug Prozac
The antidepressant drug Prozac. ‘There is no convincing evidence that depression is caused by serotonin abnormalities,’ the researchers said. Photograph: Christian Hopewell/Alamy
The antidepressant drug Prozac. ‘There is no convincing evidence that depression is caused by serotonin abnormalities,’ the researchers said. Photograph: Christian Hopewell/Alamy

Little evidence that chemical imbalance causes depression, UCL scientists find

This article is more than 1 year old

Researchers question use of antidepressants, prescribed to one in six UK adults

Scientists have called into question the widespread use of antidepressants after a major review found “no clear evidence” that low serotonin levels are responsible for depression.

Prescriptions for antidepressants have risen dramatically since the 1990s, with one in six adults and 2% of teenagers in England now being prescribed them. Millions more people around the world regularly use antidepressants.

“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,” said the study’s lead author, Joanna Moncrieff, a professor of psychiatry at University College London and consultant psychiatrist at North East London NHS foundation trust.

“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.

“Thousands of people suffer from side-effects of antidepressants, including the severe withdrawal effects that can occur when people try to stop them, yet prescription rates continue to rise. We believe this situation has been driven partly by the false belief that depression is due to a chemical imbalance. It is high time to inform the public that this belief is not grounded in science.”

The new review of existing studies found that depression is not likely to be caused by a chemical imbalance and said people should be made aware of other options for treating it.

However, other experts, including from the Royal College of Psychiatrists, questioned the findings and urged people not to stop taking their medication in light of the study, arguing that antidepressants remained effective.

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In the new analysis, researchers said 85% to 90% of the public believed depression was caused by low serotonin or a chemical imbalance.

Most antidepressants are selective serotonin reuptake inhibitors (SSRIs), originally said to work by correcting abnormally low serotonin levels.

The review, published in the journal Molecular Psychiatry, looked at studies examining serotonin and depression involving tens of thousands of people. One of the findings was that research comparing levels of serotonin and its breakdown products in the blood or brain fluids did not discover any difference between people diagnosed with depression and healthy people.

The authors also looked at studies where serotonin levels were artificially lowered in hundreds of people and concluded that lowering serotonin in this way did not produce depression in hundreds of healthy volunteers.

Other studies looked at the effects 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 importance of external events.

According to the research, there is also evidence from other studies that antidepressants may actually induce low serotonin in the long term.

“Our view is that patients should not be told that depression is caused by low serotonin or by a chemical imbalance, and they should not be led to believe that antidepressants work by targeting these unproven abnormalities,” said Moncrieff.

“We do not understand what antidepressants are doing to the brain exactly, and giving people this sort of misinformation prevents them from making an informed decision about whether to take antidepressants or not.”

A spokesperson for the Royal College of Psychiatrists said: “Antidepressants are an effective, Nice-recommended treatment for depression that can also be prescribed for a range of physical and mental health conditions. We would not recommend for anyone to stop taking their antidepressants based on this review, and encourage anyone with concerns about their medication to contact their GP.”

Dr Michael Bloomfield, a consultant psychiatrist and principal clinical research fellow at University College London, who was not involved in the study, said: “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.”

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