Most antidepressants on the market have the effect of increasing levels of the neurotransmitter serotonin, but that’s not the cause of depression, according to a rigorous new study.
About 3.5 million people in Spain take antidepressant medication. For years, psychiatrists around the world have hypothesized that depressive disorder is due to a “chemical imbalance” in the brain. Supposedly, people suffering from depression lack the neurotransmitter serotonin, which is responsible, among other things, for a sense of well-being. So, with a pill that increases serotonin levels, depression should go away. The problem is that none of these assumptions have proven to be true.
A new overview – a summary of existing meta-analyses and systematic reviews – published in Nature Molecular Psychiatrysuggests that depression is not caused by a chemical imbalance, and questions the role of antidepressants.
Most antidepressants act as selective serotonin reuptake inhibitors (SSRIs). Since it is not possible to take serotonin directly, these drugs increase its levels by preventing its reabsorption by the neuron that secretes it. The most well-known antidepressants, such as fluoxetine (the famous Prozac), citalopram, escitalopram (Lexapro), fluvoxamine, paroxetine and sertraline.
All of these drugs were originally said to work by correcting abnormally low levels of serotonin. There is no other accepted pharmacological mechanism by which antidepressants affect symptoms of depression. However, the new study rules out that low serotonin levels are the cause of depression.
“There is no convincing evidence that depression is caused by lower serotonin levels.”
Lead author Professor Joanna Moncrieff, Professor of Psychiatry at University College London and Consultant Psychiatrist at the North East London NHS Foundation Trust (NELFT), says: “We can safely say that, after much research over several decades, there is no evidence that depression is caused by serotonin abnormalities, particularly lower levels or reduced activity of serotonin.”
For example, a 2007 meta-analysis and a sample of recent studies involving hundreds of healthy volunteers found that reducing serotonin by depriving participants of an amino acid in their diet necessary for its synthesis in the body does not cause depression.
The researchers say their findings are important, as studies show that up to 85-90% of the public believe depression is caused by low serotonin or a chemical imbalance. A growing number of scientists and professional organizations recognize that the chemical imbalance structure is an oversimplification.
The popularity of the “chemical imbalance” theory of depression has coincided with a huge increase in the use of antidepressants, the use of which in Spain has multiplied fourfold in the last two decades, as well as in other neighboring countries. The world market for antidepressants produces about revenue of about $15.6 billion in 2020of which a third correspond to SSRIs.
Questions about the effectiveness of SSRI antidepressants
The effectiveness of SSRIs against depression has been the subject of controversy for decades. Two meta-analyses published in 2008 s 2010 found that in mild and moderate depression, the effect of SSRIs is small or none compared to placebo, while in very severe depression the effect of SSRIs ranged only from “relatively small” to “substantial”. The authors attributed the association between severity and efficacy to a reduction in the placebo effect in severely depressed patients, rather than an increase in medication effect.
ONE 2012 meta-analysis on fluoxetine and venlafaxine concluded that the treatment effects were significant relative to placebo, however, some of the authors revealed substantial conflicts of interest with the pharmaceutical industry.
ONE 2017 systematic review states that while SSRIs appear to have statistically significant effects over placebo in studies, the clinical significance of these effects “seems questionable” and “all trials were at high risk of bias.”
In this same study, SSRI antidepressants are shown to significantly increase the risk of serious adverse effects, which “appear to outweigh any small potential beneficial effect”. Side effects of SSRIs include sexual dysfunction (very common) which includes low libido, anorgasmia and erectile dysfunction, increased risk of suicide, akatasia -a disorder that consists of being unable to keep quiet-, increased risk of osteoporosis and fractures, and increased risk of glaucoma, coronary diseases, between others.
In addition, SSRI antidepressants produce a withdrawal syndrome when taken that include symptoms such as sleep problems, nausea, imbalance, sensory changes, anxiety and depression and, in the most severe cases, psychosis.
REFERENCE
The serotonergic theory of depression: a systematic review of the evidence