2026 ECNP Congress

PS04-4128

When dissociation shapes experience: the impact of altered states on post-esketamine well-being

Delia-Andreea Nechifor — E. Stan, S.H. Morosan, M. Ferencz, A. Mihai · Mures County Clinic Hospital, Psychiatry I-Acute, Targu Mures, Romania

2026 ECNP Congress

Background: While still being a relatively new therapeutic alternative, intranasal administered esketamine has gained solid evidence in treating Treatment Resistant Depression (TRD) through its primary action on NMDA receptors which leads to raised synaptic plasticity, downstream glutamatergic modulation and rapid antidepressant effect [1], [2]. As one of its most important and studied secondary effects, dissociation remains misunderstood in terms of phenomenology, subjective perception of the patients and how it shapes the lens through which the patients see the therapeutic process and even themselves.

Aim: To examine whether the qualitative characteristics of dissociative experience and its interpretation during and after esketamine treatment may influence the subjective well-being after administration on short and long-term.

Methods: The case report represents a naturalistic longitudinal observation. We have examined a 57-year old female patient diagnosed with Major Depressive Disorder since 2014, who was treated with SSRI and SNRI with mild amelioration of symptomatology. During the year 2024, intranasal esketamine treatment was initiated at 28 mg during the initial session, followed by escalation to 56 mg and subsequently 84 mg in later sessions, based on good tolerability. During the session, she was listening to music on the headphones and after 2 hours of monitorization, she recorded the dissociative experience in a notebook where she noted how it felt for her, what she had seen, the time passed between the administration and the onset of dissociation, how the phenomenon affected her post-session subjective state.

Results: The dissociative effect lasted approximately 40 min and was not accompanied by anxiety partly due to her listening to music during the monitorization, helping her to positively go through the experience and accept it. A dose-related increase in intensity of perceptual phenomena was observed following the escalation from 56 mg to 84 mg. During the dissociative episodes, she experienced perceptual alterations and depersonalization. The complexity of the imagery proportionally grew with the increase of the dose from the first 3 sessions to the next 5 ones and varied from naturalistic sights (mountains, rivers, animals, the Sun, two irises) to reviewing personal life events (the relationship with her first husband, seeing her dead parents). Furthermore, the patient’s post-treatment subjective state seemed to vary in relation to the content of the dissociation and its interpretation during and after the dissociative experience. The particularity of this case is the more nuanced role that the dissociation may play in the therapeutic process. Exploring the perceptual alterations can offer a valuable insight into the therapeutic valence of the patient’s subjective imagery.

Conclusions: Taking into account that the quality of the dissociation and its meaningful interpretation improved the well-being of the patient in a positive way, it opens the door for a future therapeutic use of dissociation as a guided method to obtain more clarity and, consequently, a lasting post-session state of wellness [3], [4], [5].

References

  1. Canuso, C.M., Singh, J.B., Fedgchin, M., Alphs, L., Lane, R., Lim, P., Pinter, C., et al., 2018. Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide. Am. J. Psychiatry 175(7), 620–630.
  2. Pardossi, S., Fagiolini, A., Cuomo, A., 2024. Variations in BDNF and their role in the neurotrophic antidepressant mechanisms of ketamine and esketamine: a review. Int. J. Mol. Sci. 25(23), 13098.
  3. Breeksema, J.J., Niemeijer, A., Kuin, B., et al., 2023. Phenomenology and therapeutic potential of patient experiences during oral esketamine treatment for treatment-resistant depression: an interpretative phenomenological study. Psychopharmacology 240, 1547–1560.
  4. Ballard, E.D., Zarate, C.A., 2020. The role of dissociation in ketamine’s antidepressant effects. Nat. Commun. 11, 6431.
  5. Sarasso, P., Billeci, M., Ronga, I., Raffone, F., Martiadis, V., Di Petta, G., 2024. Disembodiment and affective resonances in esketamine treatment of depersonalized depression subtype: two case studies. Psychopathology 57(6), 480–491.