THE MYTH OF SEROTONIN THEORY OF DEPRESSION: AN ANALYSIS OF UMBRELLA REVIEW METHODOLOGIES AND CLINICAL IMPLICATIONS.

Abstract

The serotonin theory of depression, long a dominant paradigm in psychiatry, has been recently challenged by a comprehensive umbrella review by, which concludes that there is no consistent evidence linking serotonin activity to depressive disorders. This article critically analyzes that review alongside two major commentaries that raise substantial methodological and interpretative concerns. Focusing on review design, inclusion criteria, quality assessment tools, and neuropharmacological interpretations, we highlight the extent to which methodological limitations can shape the conclusions of evidence syntheses. While Moncrieff's work provokes valuable scientific debate, its post-hoc protocol amendments, selective reporting, and down-weighting of serotonergic findings weaken its conclusiveness. We argue for a more nuanced understanding of serotonin's role in depression, not as a sole cause but as a potential modulatory factor in vulnerable populations. The implications for clinical practice and public communication are discussed.