The conventional wisdom in psychiatry is being turned on its head. For decades, doctors have accepted the hypothesis that serotonin levels in our brains are responsible for depression. A new umbrella review of the existing studies debunks that hypothesis.
First, if you are currently taking SSRIs, consult with your physician or psychiatrist before discontinuing your prescription.
After decades of research, the studies show that no clear evidence exists for serotonin levels or serotonin activity is responsible for depression.
This umbrella review was conducted by a research group at University College London, which was led by Joanna Moncrieff, a professor of psychiatry at the school. Her team reviewed multiple meta-analyses and systematic reviews and concluded that depression is not likely caused by a chemical imbalance. Their article was published in Molecular Psychiatry and called into question what popular antidepressants actually accomplish.
Most antidepressants are selective serotonin reuptake inhibitors (SSRIs), which were originally thought to work by correcting abnormally low serotonin levels. There is no other accepted pharmacological mechanism by which antidepressants affect the symptoms of depression.
Moncrief said: “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.
“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.
“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.”
Their review sought to include all relevant studies that have been published in the fields of serotonin and depression. The studies in the umbrella review included tens of thousands of participants.
Research comparing serotonin levels and its breakdown products in the blood or brain fluids did not find a difference between people diagnosed with depression and healthy participants.
Research on serotonin receptors and the serotonin transporter, the protein targeted by most antidepressants, found weak and inconsistent evidence that would be suggestive of higher levels of serotonin activity in people with depression. The researchers noted that these findings may be explained by the use of antidepressants in people with depression since the effects had not been ruled out.
Notably, the team also investigated studies in which serotonin levels were artificially lowered in people by eliminating from their diets the amino acid required to make serotonin. These studies have been used to suggest that serotonin deficiency is linked to depression.
However, a meta-analysis in 2007 found that lowering serotonin levels in this manner did not produce depression in its healthy participants. There was weak evidence is a very small subgroup with a family history of depression. This subgroup was only 75 people. More recent evidence is inconclusive.
Other large studies investigated gene variations including the gene for the serotonin transporter. They found no difference in these genes between people with depression and healthy controls.
These studies did look at the impact of stress and life events. They found these to be indicators and have a strong impact on the risk of becoming depressed. The more stressful life events a person had, the more likely they were to become depressed. Large, comprehensive studies looked at stressful life events, the type of serotonin transporter gene, and the risk of developing depression. Although some earlier studies suggested a link, subsequent studies debunked those apparent links.
These findings together led the authors to conclude that there is “no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations.”
Surveys show that up to 90% of the public believe that depression is caused by a chemical imbalance or low serotonin levels. In addition, evidence shows that believing that depression is caused by a chemical imbalance causes patients to be pessimistic about recovery. Patients begin to believe that only medical intervention will work.
An increasing number of scientists are beginning to reject the hypothesis of chemical imbalance or low serotonin in depression.
The authors also found evidence from a large meta-analysis that people who used antidepressants had lower levels of serotonin in their blood. They concluded that some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentrations.
This could be truly bad news. While SSRIs may work initially, long term use may produce the opposite effect of worsening depression.
The authors of the study suggested this new information should encourage further research into methods of managing stress and trauma without medications. This might include cognitive behavioral therapy, talk therapy, or psychotherapy along with physical exercise or practicing mindfulness. They also suggested addressing the underlying contributors to depression like loneliness, stress, or poverty among other issues.
Professor Moncrieff said: “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 Dr Mark Horowitz, a training psychiatrist and Clinical Research Fellow in Psychiatry at UCL and NELFT, 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.”
Professor Moncrieff added: “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.”