Disembodiment and Affective Resonances in Esketamine Treatment of Depersonalized Depression Subtype: Two Case Studies.

Dissociative experiences from ketamine, often seen as undesirable side effects, may be essential for its antidepressant action in certain depression subtypes. The 'relaxed prior hypothesis' proposes that ketamine enhances sensitivity to bodily signals by blocking glutamate, improving short-term plasticity. Two patients with 'depersonalized depression' (Entfremdungsdepression) in a six-month esketamine program showed that induced dissociation, particularly disembodiment, could suspend ingrained patterns of feeling and behavior. This creates a window of psychological plasticity, allowing the body to regain responsiveness to emotional cues. The findings suggest esketamine's dissociative effects may be especially beneficial for those with compromised interoceptive awareness and interaffectivity.

Study at a glance

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.