Podcast: Treatment Resistance, Placebo Response, and What Comes Next With Maurizio Fava, MD
Maurizio Fava, MD, discusses treatment-resistant depression, the placebo response, ketamine research, mentorship, and where AI fits into psychiatry's future.
“Psychopharm Today” is a video-podcast series, created collaboratively with the
In this episode of “Psychopharm Today,” guest Maurizio Fava, MD, sat down for a wide-ranging conversation with host Michael E. Henry, MD, about the career instincts and collaborations that have shaped his decades-long work on treatment-resistant depression, placebo response, and ketamine.
Fava traced his focus on treatment-resistant depression back to his early years at Massachusetts General Hospital, where he made it known he wanted to see patients with depression. Over time, colleagues began referring him increasingly complex cases—patients who had already failed multiple treatments rather than straightforward, first-episode cases. That pattern led him to recognize an underserved population of non-responders and to develop what he calls the MGH staging method, a framework for distinguishing patients with no treatment resistance from those who have failed numerous prior therapies.
Asked about other pivotal insights in his career, Fava described his "aha moments" as typically arising during relaxed, unstructured time—he specifically mentioned walking on the beach collecting shells. One such moment came from observing that placebo response tends to occur in the first half of a clinical trial regardless of the trial's total length. This observation prompted him to design a trial methodology that re-randomizes patients after an initial placebo response. Working with biostatistician David Schoenfeld, he developed the sequential parallel comparison design (SPCD), which has since been used in more than 40 multicenter trials and meaningfully reduces placebo response rates.
When asked how he has sustained a high level of productivity and impact across multiple research areas, Fava attributed it to collaboration, describing clinical research as a "team sport"—a mentality he traces back to playing team sports as a child. He emphasized that outstanding collaborators make it possible to achieve goals no one could reach alone.
Turning to mentorship, Fava encouraged medical students to consider psychiatry, citing an exciting era ahead driven by new molecules, devices, and psychotherapies stemming from neuroscience and genetics research, as well as a significant US psychiatrist shortage (he cited a gap of more than 14,000) that all but guarantees strong job prospects. He said contributing to the development of new compounds—even in small ways—is what most motivates him day to day.
On artificial intelligence, Fava advised early-career psychiatrists to embrace AI as a tool without letting it dominate the profession, emphasizing that clinicians must remain in control of AI rather than the reverse. His central worry is that AI could position itself as a standalone treatment solution; he referenced cases where people died after relying solely on a chatbot for care, warning against patients delegating their health entirely to AI. For mid-career psychiatrists less versed in the technology, he recommended learning from younger colleagues who have already mastered these tools, predicting that using AI in some form will soon be unavoidable in psychiatric practice.
Dr Henry is a psychiatrist at Mass General Brigham Hospital and medical director of the Dauten Family Center for Bipolar Treatment Innovation.
Dr Fava is psychiatrist-in-chief of the Department of Psychiatry at Massachusetts General Brigham Academic Medical Center.
