PsychRounds: The Psychiatry Podcast Ketamine/Esketamine (Spravato) with Dr. Joshua Rosenblat
Apr 1, 2025
Dr. Joshua Rosenblat, a clinician-researcher at the University of Toronto, discusses the groundbreaking role of ketamine and its derivative, esketamine, in treating treatment-resistant mood disorders. He highlights their quick effectiveness compared to traditional antidepressants and reviews the historical journey of ketamine's usage. Exploring barriers to accessibility in psychiatric care, he advocates for innovative solutions, while also addressing safety and efficacy across different age groups. It's a deep dive into transformative therapies that could reshape mental health treatment.
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Serendipitous Ketamine Discovery
- Ketamine's discovery in psychiatry was serendipitous, first studied broadly in the 1970s and then as an antidepressant in 2000 with robust rapid effects.
- Its effect was initially noticed when studying it as a schizophrenia model, where mood elevation was an unexpected finding.
Ketamine's Multifaceted Mechanism
- Ketamine acts through multiple mechanisms including glutamate modulation, opioid receptor effects, and impacts on other neurotransmitter systems.
- Its antidepressant effects likely arise from a concerted set of mechanisms rather than NMDA antagonism alone.
S-Ketamine vs Racemic Ketamine
- S-ketamine was selected for FDA approval mainly due to stronger NMDA affinity and bioavailability via nasal route, avoiding IV and oral administration issues.
- Comparative clinical evidence is inconclusive; ongoing trials are investigating whether racemic ketamine might be more effective than S-ketamine.