FOr over three decades, people have been flooded with information suggesting that depression is caused by a “chemical imbalance” in the brain—namely an imbalance of a brain chemical called serotonin. However, our latest research review Shows that the evidence does not support it.
Although previously proposed in the 1960sThe serotonin theory of depression began to be widely promoted by the pharmaceutical industry in the 1990s in collaboration with its efforts to market a new class of antidepressants, known as selective serotonin-reuptake inhibitors, or SSRIs. The idea was also supported by official institutions such as the American Psychiatric Association, which still tells the public that “differences in certain chemicals in the brain may contribute to symptoms of depression”.
Countless doctors have repeated this message all over the world, in their private surgeries and in the media. People accepted his word. And many started taking antidepressants because they believed there was something wrong with their brains that needed an antidepressant to correct. In the period of this marketing push, antidepressant use increased dramatically, and they are now Determined to one in six adult populations in EnglandFor example.
For a long time, some academicsincluding some chief psychiatristhave suggested that there is no satisfactory evidence to support the idea that depression is the result of abnormally low or underactive serotonin. other continues support the theory, So far, however, there has been no comprehensive review of the research on serotonin and depression that would in any way enable firm conclusions.
At first glance, the fact that SSRI-type antidepressants act on the serotonin system appears to support the serotonin theory of depression. SSRIs temporarily increase the availability of serotonin in the brain, but this does not necessarily lead to the opposite effect of depression.
There are other explanations for the effects of antidepressants. In fact, drug trials show that antidepressants are Barely distinguishable from placebo (dummy pill) when it comes to treating depression. In addition, antidepressants seem to have a generalized emotion-numbing effect Which can affect people’s moods, although we don’t know how or much about this effect.
first comprehensive review
There has been extensive research on the serotonin system since the 1990s, but it has not previously been systematically collected. we held a “Umbrella” Review That involved systematically identifying and matching existing observations of evidence to each of the main areas of research into serotonin and depression. Although there has been a systematic review of individual regions in the past, none has combined the evidence from all the different regions that have adopted this approach.
One area of research we covered involved research comparing the levels of serotonin and its breakdown products in the blood or brain fluid. Overall, this research did not show a difference between people with depression and people without depression.
Another area of research has focused on serotonin receptors, which are proteins at the ends of nerves that bind to serotonin and which can transmit or inhibit the effects of serotonin. The most investigated research on the serotonin receptor suggested that either there is no difference between people with depression and people without depression, or that serotonin activity was actually increased in people with depression – similar to the prediction of the serotonin theory. Adverse.
research on Serotonin “Transporter”, the protein that helps to exert the effects of serotonin (this is the protein on which SSRIs act), also suggested that, if anything, there was increased serotonin activity in people with depression. . However, these findings may be explained by the fact that many of the participants in these studies had used or were currently using antidepressants.
We also looked at research that explored whether depression could be induced in volunteers. artificially lowering serotonin levels, two systematic reviews from 2006 And 2007 And a sample of the ten most recent studies (at the time the current research was conducted) found that reducing serotonin did not induce depression in hundreds of healthy volunteers. one of the reviews showed very weak evidence of effect in a small subgroup of people with a family history of depression, but included only 75 participants.
Very large studies involving tens of thousands of patients looked at gene variation, including genes that have instructions to make serotonin transporter, They found no difference in the frequency of variants of this gene between people with depression and healthy controls.
Although a famous early studies An association was found between the serotonin transporter gene and stressful life events, with larger, more comprehensive studies showing that no such relationship exists. However, stressful life events in themselves had a strong effect on people’s risk of post-depression.
Some studies in our observation that included people who were taking or had previously taken antidepressants found evidence that antidepressants may actually reduce the concentration or activity of serotonin.
not supported by evidence
The serotonin theory of depression has been one of the most influential and widely researched biological theories of the origin of depression. Our study shows that this view is not supported by scientific evidence. It also raises questions about the basis for the use of antidepressants.
Most of the antidepressants in use now are believed to act through their effect on serotonin. Certain brain chemicals also affect noradrenaline. But experts agree that there is evidence that noradrenaline is involved in depression. weaker than serotonin,
There is no other accepted pharmacological mechanism for how antidepressants may affect depression. If antidepressants exert their effect as placebo or by numbing emotions, it is not clear whether they do more good than harm.
Although viewing depression as a biological disorder may seem like it would reduce stigma, in fact, Research has shown the oppositeAnd also those who believe that their own depression is due to a chemical imbalance more pessimistic about their chances of recovery.
It is important that people realize that the idea that depression results from a “chemical imbalance” is hypothetical. And we don’t understand what the serotonin or other biochemical changes temporarily produced by antidepressants do to the brain. We conclude that it is impossible to say whether taking SSRI antidepressants is worthwhile, or even completely safe.
If you are taking antidepressants, it is very important that you do not stop taking them without first talking to your doctor. But people need all this information to make an informed decision about whether or not to take these drugs.
Joanna MoncrieffSenior Clinical Lecturer, Critical and Social Psychiatry, UCL And Mark HorowitzClinical Research Fellow in Psychiatry, UCL
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