The explanation “you have a serotonin deficiency” is familiar to almost everyone who has sought help for depression. It is simple, it sounds scientific and it removes blame: the issue is not your character but your chemistry.
The problem is that this explanation is not supported by the data.
What was done
In 2022 the journal Molecular Psychiatry (Nature Publishing Group) carried a systematic umbrella review — that is, a review of reviews. The authors, led by Joanna Moncrieff, gathered more than thirty major studies, meta-analyses and systematic reviews published between 2007 and 2020 and tested all the main lines of evidence for the serotonin hypothesis.
The authors’ conclusion is stated plainly: it is time to acknowledge that the serotonin theory of depression has no empirical support.
What exactly was tested
Concentrations of serotonin and its metabolites. No convincing differences were found between people with and without depression.
Serotonin receptors and the transporter. The data are contradictory. There are weak indications of possible differences in 5-HT1A receptors, but the results may be distorted by previous antidepressant use in some participants.
Genetics. The link between serotonin-system genotypes and depression was not confirmed in large studies. Early work showing a gene–stress interaction did not replicate in large samples.
Artificially lowering serotonin. Experiments lowering tryptophan levels in healthy people do not produce depression — which would be expected if the hypothesis were correct.
What does not follow from this
It is easy to take a wrong step here, so let us be direct.
It does not follow that antidepressants do not work. Their effectiveness is tested by clinical trials, not by a theory of mechanism. A medicine can be effective even if the explanation of how exactly it works turns out to be wrong — in the history of medicine this is an ordinary situation. Aspirin was used for decades before its mechanism was understood.
It does not follow that depression is “not biological”. It is unquestionably connected with how the brain works. That connection is simply more complex than the level of one neurotransmitter.
It does not follow that you should stop prescribed treatment. Abruptly stopping antidepressants is dangerous. Any changes belong with your treating doctor.
What does follow in practice
The main consequence is not medical but psychological.
The belief “I have a chemical imbalance” sets a particular attitude to treatment: the only thing that can be done is take a medicine, and one’s own actions have no effect on one’s state. This lowers motivation for psychotherapy, weakens belief in self-regulation and makes a person a passive participant in their own treatment. In the extreme case it produces the assumption that lifelong medication is the only option.
The data say something different: depression is maintained by several mechanisms, and some of them a person can affect directly. Reduced activity, rumination, changed perception of oneself and the future — this is what cognitive behavioural therapy works with, and its effectiveness in depression is confirmed regardless of which theory of mechanism is correct.
The most durable result in moderate and severe depression comes from combining psychotherapy with medication. This is not a choice between two camps.
If this is about you
We have described how work with depression is structured on a separate page — depression and loss of energy.
If thoughts of suicide appear, do not wait for an appointment: call emergency services on 112.