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New study questions use of antidepressants – ‘No convincing evidence’ chemical imbalance causes depression

After decades of research, there remains no convincing evidence that a chemical imbalance of serotonin is responsible for depression, according to a major review of prior research led by scientists at University College London (UCL). 

Scientists behind the new study have subsequently called into question the widespread use of antidepressants amid a rise in the numbers of people being prescribed the medication, which works by balancing out chemicals in the brain called neurotransmitters that affect mood and emotion.

Scientists who conducted the major review, published on Wednesday, found “no clear evidence” that depression is caused by serotonin abnormalities.

“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. 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”, the lead researcher said.


ANTIDEPRESSANT USE RISING IN IRELAND 

The study is all the more significant as prescriptions for antidepressants have risen dramatically since the 1990s – one in six UK adults in England are now prescribed antidepressants, while 2 per cent of English teenagers are on antidepressants.

In 2018, a leading psychiatrist estimated that 10 and 12 per cent of all Irish adults were being prescribed antidepressants. Addressing the Irish Medical Organisation’s national conference that year, consultant psychiatrist Dr Matthew Sadlier said about 390,000 out of roughly 1.6 million people covered by the medical card scheme were being prescribed antidepressants.

A study published last October in the Irish Journal of Medical Science evidenced an increase in the amount of people in Ireland using antidepressants.

The study found that the use of antidepressant medication was rising amongst Irish medical card holders – with the number of those with a medical card prescribed antidepressants growing from 9.42 per cent to 12.3 per cent per 100 medical card holders in the five years between 2016-2020.

2020 represented the largest proportion of Irish medical card holder prescriptions for antidepressants, and annual figures showed a continual increase in antidepressant dispensing refill rates from 2016 to 2020.

The lead author of the new study, Joanna Moncrieff, a professor of psychiatry at University College London and consultant psychiatrist at North East London NHS Foundation Trust said:

“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.

“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”.

“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 said.

The umbrella review aimed to capture all studies of relevance that have been published on the matter in the most prominent fields of research on depression and serotonin, and the studies included in the landmark review involved thousands of participants.

Science Daily reports: “Research that compared levels of serotonin and its breakdown products in the blood or brain fluids did not find a difference between people diagnosed with depression and healthy control (comparison) participants.

“Research on serotonin receptors and the serotonin transporter, the protein targeted by most antidepressants, found weak and inconsistent evidence suggestive of higher levels of serotonin activity in people with depression. However, the researchers say the findings are likely explained by the use of antidepressants among people diagnosed with depression, since such effects were not reliably ruled out.

Further, a meta-analysis conducted in 2007 and a sample of recent studies found that lowering serotonin did not produce depression in hundreds of healthy volunteers. Very large studies which involved tens of thousands of patients explored gene variation, including the gene for the serotonin transporter.

These comprehensive studies found ‘no difference’ in the genes of people with depression and those with healthy controls. Studies also looked at the impact of stressful life events and found that these exerted a ‘strong effect’ on people’s risk of becoming depressed. The findings combined led the authors to conclude that there is “no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations”.

The researchers point to the importance of their findings in light of the fact studies show that as many as 85 to 90 per cent of the public believes that depression is caused by low serotonin levels of a chemical imbalance. The authors highlight that a growing number of scientists and professional bodies are acknowledging the chemical imbalance framing as an over-simplification.

Evidence, they recognise, also exists, that believing that low mood is caused by a chemical imbalance leads to people having a pessimistic outlook on the likelihood of recovering, and the possibility of being able to manage their moods without medical assistance; this is important as the majority of people will meet criteria for depression or anxiety at some point in their lives.

Professor Moncrieff added: “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. 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”.

Co-author of the study, Dr Mark Horowitz, a Clinical Research Fellow in Psychiatry at UCL and NELFT and a training psychiatrist, 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 and feels like everything I thought I knew has been flipped upside down.”

“One interesting aspect in the studies we examined was how strong an effect adverse life events played in depression, suggesting low mood is a response to people’s lives and cannot be boiled down to a simple chemical equation.”

The researchers also cautioned that anyone considering a withdrawal from antidepressants should seek the advice of a health professional, in light of the risk of adverse effects following withdrawal.

Professor Moncrieff and Dr Horowitz are currently conducting ongoing research into how best to gradually stop taking antidepressants.

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