Why Serotonin Isn’t Outdated, Our Thinking Is

Psychiatric drug development may be overcomplicating progress while overlooking effective treatments. Brandon Li speaks with Dr. Jacob Jacobsen, neuroscientist and CEO of Evecxia Therapeutics, about why clinical outcomes should matter more than novel mechanisms.

Jacobsen argues that the field’s fixation on discovering entirely new mechanisms has distracted from the real goal: delivering treatments that produce better clinical outcomes for patients. Drawing on decades of human clinical data, he explains how serotonin synthesis amplification builds on well-established biology to enhance the effectiveness of existing antidepressant approaches, rather than replacing them.

The conversation explores why oral, scalable treatments are essential for addressing the massive unmet need in treatment-resistant depression, especially when costly clinic-based therapies reach only a fraction of patients. Jacobsen also breaks down why OCD presents a smarter initial indication for development, with lower placebo response rates, better patient selection, and a clear regulatory gap for next-line therapies.

Brandon and Dr. Jacobsen take a candid look at the structural failures in psychiatric research, including the continued reliance on animal behavioral models that have repeatedly failed to predict human outcomes. Instead,Dr. Jacobsen advocates for a return to human biology, biomarker research, and clinically grounded trial design, approaches that prioritize real-world impact over theoretical elegance.

What You'll Learn:

- Why clinical novelty matters more than mechanistic novelty in psychiatric drug development

- How serotonin synthesis amplification can improve outcomes beyond traditional SSRIs

- The scalability advantages of oral treatments compared to clinic-based therapies like ketamine

- Why OCD is a strategically stronger indication than depression for early clinical development

- How placebo response rates distort psychiatric trial outcomes and how to reduce them

- Why animal models have repeatedly failed psychiatry and continue to slow innovation

- The importance of prioritizing human biology, biomarkers, and real-world clinical data

- How smarter trial design can reduce risk while increasing the likelihood of meaningful results

Dr. Jacob Jacobsen is a neuroscientist, inventor, and CEO of Evecxia Therapeutics. He is the originator of the serotonin synthesis amplification pharmacological concept and has led seminal cross-disciplinary research in this area. Prior to Evecxia, Jacobsen held research positions at Duke University and Duke–National University of Singapore and spent eight years in pharma-biotech at NeuroSearch and Lundbeck, working on drug discovery and target validation.

Dr. Jacobsen is widely published in leading psychiatry journals, is an inventor on multiple issued and pending patents, and holds a PhD in Neuropharmacology from the University of Copenhagen.

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