Federico Cevoli, Husseini K. Manji, Andrew H. Miller, Brenda W.J.H. Penninx, Martien Kas, Carmine M. Pariante, Livia De Picker, Paweł Świeboda, Marion Leboyer
Importance: Neuropsychiatric disorders impose a substantial burden on individuals and societies worldwide. Despite significant advances in the understanding of the brain, only a handful of mechanism-based treatments for psychiatric disorders have been discovered and validated in the past 50 years. Observations: After discussing the reasons for poor progress in drug discovery in mental disorders, this article outlines recommendations for a paradigm shift toward precision psychiatry, emphasizing the need for biomarker discovery and suggesting a reform of clinical trial methodology. To drive this transformation, increased public and private investment must be aligned with the societal impact of mental disorders, while regulatory agencies should adopt more flexible and biomarker-informed trials, as seen in oncology and other medical fields. Conclusion and Relevance: Promoting cross-sector collaboration between academia, biotech, industry, and health care systems will be critical to support high-risk, high-reward innovations. This article reflects the broad consensus of experts from academia, industry, regulatory agencies, and patient representatives to advance the agenda for precision psychiatry.