Disembodiment and Affective Resonances in Esketamine Treatment of Depersonalized Depression Subtype: Two Case Studies.
Pietro Sarasso, Martina Billeci, Irene Ronga, Fabiola Raffone, Vassilis Martiadis, Gilberto Di Petta
Psychopathology 2024 DOI: 10.1159/000539714 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case study Case report Peer reviewed |
|---|---|
| Sample size | 2 |
| Population | Patients with treatment resistant depression and depersonalized depression symptoms |
| Intervention | Esketamine |
| Duration | 6-month-long esketamine program |
| Topics | Esketamine Depression Ketamine |
| Keywords | Affective resonances Depersonalized depression Embodiment Interoceptive awareness Depression therapy Dissociative drugs Mental health treatment Psychiatric medicine Sensory perception |
| Citations | 18 |
| Key findings | Esketamine-induced dissociation and disembodiment may be particularly effective for the depersonalized depression subtype by enhancing interoceptive sensitivity and psychological plasticity. |
Abstract
Dissociative experiences are considered undesirable ketamine's adverse events. However, they might be crucial for ketamine's antidepressant effects, at least in some depression subtypes. Current understandings of ketamine's therapeutic potentials converge on the so-called "relaxed prior hypothesis," suggesting that glutamatergic blockage up-weights bottom-up surprising somatosensory/affective states. As a result, ketamine improves short-term plasticity in depression by enhancing sensitivity to interoceptive signals. We selected 2 case studies for their paradigmatic description of "depersonalized depression" (Entfremdungsdepression) symptoms. Patients were included in a 6-month-long esketamine program for treatment resistant depression, during which we collected their spontaneous experience with esketamine. According to a neurophenomenological approach, we combined subjective reports from unstructured clinical interviews and the review of previous objective neuroimaging results and neurocomputational models to unveil the relation between esketamine antidepressant effects and interoceptive sensitivity. According to our clinical observations, esketamine-induced dissociation might be particularly effective in the depersonalized depression subtype, in which interoceptive awareness and interaffectivity are particularly compromised. Ketamine and esketamine's dissociative effects and particularly disembodiment might suspend previously acquired patterns of feeling, sensing, and behaving. Coherently with previous research, we suggest that esketamine-induced disembodiment allows for a transient window of psychological plasticity and enhanced sensitivity, where the body recovers its permeability to affective affordances.
Comparable studies
Other case reports and case series on esketamine for depression, most cited first.
Citations in the library
Cited by 10
- Nature heals: An informational entropy account of self-organization and change in field psychotherapy. Physics of Life Reviews December 1, 2024
- The Effects of Psychotherapy on Single and Repeated Ketamine Infusion(s) Therapy for Treatment-Resistant Depression: The Convergence of Molecular and Psychological Treatment. International Journal of Molecular Sciences July 11, 2025
- Long-Term Effects of Single and Repeated Ketamine Infusions on Treatment-Resistant Depression: A Retrospective Chart Review Study Psychoactives October 12, 2024
- Ketamine-assisted group psychotherapy integrating cognitive processing therapy to address identity-based trauma: a pilot study Frontiers in Psychiatry January 22, 2026
- Case Report: A possible association between significant dissociations after esketamine treatment and histrionic personality disorder Frontiers in Psychiatry December 17, 2025
and 5 more in the library
Cites 50
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- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate British Journal of Pharmacology June 1, 1983
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
and 45 more in the library