For decades, it has been the mainstream view that depression is caused by a deficiency in serotonin. This belief is prevalent within medical literature and the lay public; abnormal levels of certain chemicals called neurotransmitters can result in the manifestation of psychological disorders. A newly published study in Molecular Psychiatry by researchers at University College London (UCL) revealed no clear evidence linking depression and serotonin activity, thus calling the effectiveness of antidepressants into question.
Serotonin, commonly referred to as the ‘happiness hormone', is a neurotransmitter that sends signals between nerve cells in the brain. Some of the neurobiological processes regulated by serotonin include memory, digestion, sleep, and learning, along with its most well-known role as a mood stabiliser. Healthcare professionals typically prescribe selective serotonin reuptake inhibitors (SSRIs) as a form of antidepressant medication to those diagnosed with depression, which operates by increasing the level of serotonin in the brain.
Lead author Joanna Moncrieff, Professor of Psychiatry at UCL and a Consultant Psychiatrist at North East London NHS Foundation Trust, argues that the serotonin theory of depression was heavily publicised by pharmaceutical companies in efforts to market SSRIs during the 1990s. “Countless doctors have repeated the message all over the world, in their private surgeries and in the media. People accepted what they were told. And many started taking antidepressants because they believed they had something wrong with their brain that required an antidepressant to put right,” she states.
The authors reviewed historical scientific literature exploring the relationship between serotonin and depression, an undertaking that combined massive amounts of data gathered from over tens of thousands of participants.
Studies that compared levels of serotonin and its breakdown products (in the blood or brain fluid) did not report notable differences between the healthy control group and participants clinically diagnosed with depression. Research examining gene variation between the two groups (particularly, the gene encoding the serotonin transporter) also found weak and inconsistent evidence, with more emphasis being placed on stressful life events as a subsequent risk in the development of depression. Experiments in which researchers artificially lowered the level of serotonin in healthy individuals were also investigated; two large-scale systematic reviews indicated no significant impact in inducing depressive symptoms in hundreds of healthy volunteers.
Some studies even reported significantly decreased levels of serotonin in people using antidepressants to combat their depression, with authors suggesting that long-term usage of SSRIs eventually reduces the concentration of serotonin in the brain. Despite its seeming effectiveness in the short-term, its consumption may produce opposite effects in the long-term due to compensatory mechanisms in the brain.
The combined findings led the authors to conclude that the current evidence surrounding the biochemical theory of depression was not convincing enough. “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,” Moncrieff adds.
Regardless of the converging evidence, the authors caution that people should not stop using antidepressants immediately due to the high risk of adverse effects after withdrawal. Any efforts to discontinue the use of medication should always be done with the consultation of a healthcare professional first. Moncrieff, along with other scientists at UCL, are currently conducting ongoing research into the best course of action to gradually taper the use of antidepressants.
