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Racemic Ketamine vs Esketamine in Treatment-Resistant Depression: The Overlooked Role of Arketamine (Tan, et al, 2025)

Evidence suggests that "IV racemic ketamine is more effective than IN esketamine in TRD; convergent preclinical and clinical findings support the hypothesis that arketamine plays a key role in this superiority and that ketamine’s antidepressant mechanisms extend beyond simple NMDAR antagonism."
Michael DeMarco, PhD

by Michael DeMarco, PhD

Racemic Ketamine vs Esketamine in Treatment-Resistant Depression: The Overlooked Role of Arketamine
The authors comment on a recent chart review by Meisner et al.
The Journal of Clinical PsychiatryTNQ Technologies

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The Role of Psychedelics in the Treatment of Substance Use Disorders: An Overview of Systematic Reviews (Correa de Costa, et al, 2025)

"...evidence suggests that the use of serotonergic and non-serotonergic psychedelics (ketamine) for the treatment of SUD may provide advantages over traditional therapeutics, and these compounds may eventually become part of the next generation of treatments for SUD under specific circumstances."

Spotlight: A long, strange trip: Ketamine treatment in psychiatry (Nutt, et al, 2025)

"...mystical experiences were strongly related to immediate and sustained psychiatric benefits at the group level and on an individual, session-by-session basis across the six doses, providing mechanistic support for ketamine-psychotherapy pairings."

Spotlight: Rapid-acting NMDA and GABAergic Modulators in Mood Disorders: From Synaptic Mechanisms to Clinical Practice (Serretti, 2025)

"Depression is increasingly conceptualized as a disorder of impaired synaptic plasticity and excitation-inhibition imbalance within corticolimbic circuits. Ketamine, brexanolone, zuranolone, offer complementary approaches to restore circuit function."

Spotlight: Personality profiles and trauma history in ketamine therapy for mood and anxiety disorders: A latent profile analysis of short-term outcomes (Gregoire, et al, 2025)

"Personality traits relate to baseline mental health severity but not short-term response to ketamine. Trauma history may predict greater benefit from treatment."

Spotlight: Changing your mind: neuroplastic mechanisms underlying the therapeutic effect of psychedelics in depression, PTSD, and addiction (Palhas, et al, 2025)

"Serotonergic psychedelics & ketamine appear to share common cellular mechanisms. They both recruit glutamatergic neurons to stimulate BDNF-trKB signaling, promoting synaptogenesis via the mTOR pathway. These changes may explain their efficacy in depression, anxiety, PTSD, & addiction."

How does ketamine affect psychotherapy?

Studies suggest that human support is a factor in ketamine psychedelic therapy
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