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The depression would not be due to the deficit of serotonin targeted by the antidepressants finally


After decades of studies, there is still no evidence that an imbalance of serotonin is responsible for depression, believe the authors of an analysis published in July 2022 in the journal Molecular Psychiatry.

Joanna Moncrieff, professor of psychiatry at theUniversity College Londonand his colleagues (1) conducted a general review of existing meta-analyses and systematic reviews of the scientific literature.

Most antidepressants are selective serotonin reuptake inhibitors (SSRIs), which were originally said to work by correcting abnormally low levels of serotonin. There is no other recognized pharmacological mechanism by which antidepressants act on the symptoms of depression.“.

It’s always hard to prove a negative, but I think we can safely say that after a great deal of research over several decades, there is no convincing evidence that depression is caused by serotonin abnormalities. , especially by lower levels or reduced activity“says the researcher.

The popularity of the “chemical imbalance” theory of depression has coincided with a dramatic increase in the use of antidepressants. Antidepressant prescriptions have risen dramatically since the 1990s, with one in six adults in England and 2% of teenagers now being prescribed an antidepressant in any given year“, reports the release of the researchers.

Research that compared levels of serotonin and its breakdown products in blood or brain fluids did not find a difference between people diagnosed with depression and healthy control participants.

Very large studies involving tens of thousands of patients have looked at gene variation, including the serotonin transporter gene. They found no difference in these genes between people with depression and healthy controls. These studies also looked at the effects of stressful life events and found that these had a strong impact on the risk of depression: the more stressful events a person had experienced, the more likely they were to be depressed. .

All of these results led the authors to conclude thatthere is no support for the hypothesis that depression is caused by decreased activity or serotonin levels“.

Studies show that 85-90% of the public believe that depression is caused by low serotonin levels or a chemical imbalance. So “that a growing number of scientists and professional bodies recognize that the chemical imbalance framework is an oversimplification. There is also evidence that the belief that depressed mood is caused by a chemical imbalance leads people to have a pessimistic view of the likelihood of recovery and the possibility of managing moods without medical help.“, underline the authors. (Thriving after a depressive, anxiety, bipolar or other disorder)

The authors also found evidence in a large meta-analysis that people who used antidepressants had lower blood serotonin levels. They concluded that some evidence was consistent with the possibility that long-term use of antidepressants reduces serotonin levels. This could imply that the increase in serotonin that some antidepressants produce in the short term could lead to compensatory changes in the brain that produce the opposite effect in the long term.

Although the study did not examine the effectiveness of antidepressants, the authors encourage further research and treatment advice that may instead focus on managing stressful or traumatic events in people’s lives, such as psychotherapy, alongside other practices such as physical activity or mindfulness, or addressing underlying factors such as poverty, stress and loneliness.

We believe that patients should not be told that depression is caused by low serotonin or a chemical imbalance, and that they should not be led to believe that antidepressants work by targeting these unproven abnormalities.“said the researcher. “We don’t understand exactly what antidepressants do to the brain, and giving people this kind of misinformation prevents them from making an informed decision about whether or not to take antidepressants.»

During my training in psychiatry, I had been taught that depression was caused by low serotonin levels and I even taught this to students in my own classes.“, reports Mark A. Horowitz, co-author. “Participating in this research has opened my eyes and I feel like everything I thought I knew has been turned upside down.»

An interesting aspect of the studies we reviewed was the importance of the influence of life events on depression, suggesting that depressed mood is a reaction to people’s lives and cannot be reduced to a simple chemical equation.»

Thousands of people suffer from the side effects of antidepressants, including the severe withdrawal effects that can occur when people try to stop taking them, yet prescription rates continue to risesays Joanna Moncrieff. “We believe this is partly due to the false belief that depression is caused by a chemical imbalance. It is high time to inform the public that this belief is not based on science.» (Quitting and weaning off antidepressants: news)

The researchers caution that anyone considering weaning off antidepressants should seek the advice of a healthcare professional, given the risk of adverse effects after withdrawal. Professor Moncrieff and Dr. Mark A. Horowitz are currently conducting research on the best way to gradually stop taking antidepressants.

For more information on depression and antidepressants, see the links below.

(1) Ruth E. Cooper, Tom Stockmann, Simone Amendola, Michael P. Hengartner, Mark A. Horowitz.

Psychomedia with sources: University College London, University College London (The Conversation), Molecular Psychiatry.
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