Putting serotonin in its place—again

Beyond discrediting the idea that depression is caused by a deficiency of serotonin amenable to “correction” by antidepressants, the review by Moncrieff et al1 mentioned by Kendrick and Collinson2 goes further in challenging the role of biology in mood disorders. Their dismantling of the serotonin “chemical imbalance” theory and its shameless promotion by the drug industry is justified, but the same cannot be said of their more general critiques of drug treatments in psychiatry.

As is often the case with high profile articles, there are risks of over interpreting the review’s findings. Firstly, they don’t prove that serotonergic antidepressants are ineffective (efficacy doubts already abound, notably for severe depression) but rather that their mechanism, when they do work, does not depend on a pre-existing serotonergic abnormality.3

Secondly, the review downplays evidence that people with personal or family histories are differentially sensitive to serotonin depletion4 and neglects a key subgroup more likely to respond to physical treatments—namely, people with melancholic depression.

Finally, the review doesn’t consider evidence that impaired serotonergic function is associated with depression during the premenstruum5 and interferon treatment or other causes of cytokine activation.6

Serotonin thus deserves to remain in the popular lexicon, but in a rather more nuanced role. Some doctors and many patients are understandably reluctant to abandon the reassuring idea of an imbalance warranting correction. We should encourage all parties to give up this convenient but misleading notion in favour of more valid narratives, both biomedical and psychosocial. Essential roles for serotonin release and receptor activation are implicated in the resolution of post-traumatic stress disorder—for example, by the combination of methylenedioxymethamphetamine and psychotherapy.7 More fundamentally, a paradigm shift in psychiatry is emerging based on evidence that promotion of neuroplasticity is a mechanism common to various therapeutic modalities—including those active in the serotonergic system.8