In episode 53, we move out of the sterile lab and into the messy real world, examining a large naturalistic study of 224 patients from an Austin clinic. The paper by Kosted and colleagues compares standard “infusion-only” ketamine treatment against Ketamine-Assisted Therapy (KAT) to answer a costly question: is paying for a therapist to be in the room actually worth it?

The average results were shocking: across the entire sample, the therapy group didn’t fare any better than the infusion-only group. But when researchers sliced the data by age and Adverse Childhood Experiences (ACEs), a much more complex story emerged. We unpack the counterintuitive “super responder” effect, where patients with high childhood trauma saw the most dramatic biological healing. For young adults under 30, the medicine alone was often more effective, suggesting that talk therapy might actually interrupt the “bake” of neuroplasticity by shifting activity to the analytical brain too soon. Conversely, for patients over 50, therapy was essential; without a human connection to help navigate and rewire decades of compensatory behaviors, the ketamine alone often fell short.

Finally, we discuss the practical implications of the “decelerating curve” of improvement—where the most dramatic drops in depression occur early in treatment—and why the future of personalized psychiatry must look beyond DNA to a patient’s lived biography.

Reference:

Kosted, R., Waddell, A., Adolph, K., & Fonzo, G. A. (2026). Age-related moderation of adjunctive psychotherapy and early life stress effects on depression symptom reductions following ketamine treatment: Initial insights from a large, naturalistic sample. Journal of Affective Disorders, 402, 121350. https://doi.org/10.1016/j.jad.2026.121350

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