In treatment-resistant depression, esketamine—a glutamatergic modulator approved in 2019—may improve not only depressive symptoms but also key psychological factors such as mentalization, psychache, social cognition, suicidality, and cognitive-emotional rigidity. In a six-month observational study of 36 patients with treatment-resistant depressive episodes, depressive symptoms significantly decreased, as measured by the Montgomery-Åsberg Depression Rating Scale. By six months, 69% of patients achieved remission, indicating a robust and sustained response. The findings suggest esketamine may be particularly beneficial in reducing cognitive rigidity and improving mentalization, potentially breaking the inflexible thinking patterns that sustain depression. Personalized treatment approaches are emphasized.
During intranasal esketamine treatment for treatment-resistant depression, patients describe four distinct types of dissociative experiences: sensory alteration and perceptual flow (27.8%), time suspension and chronological drift (58.3%), body and space alteration (55.6%), and psychic distance from suffering (83.3%). Most patients frame these experiences as neutral or meaningful, often linked to temporary relief from rumination and depressive distress, though a minority report transient distress or loss of control. The findings suggest dissociation functions as a transitional subjective state whose clinical relevance depends on anticipation, framing, monitoring, and integration, supporting structured psychoeducation and in-session support in esketamine programs.