Pôle Hospitalo-Universitaire Psychiatrie Paris 15, GHU Paris Psychiatrie et Neurosciences, Hôpital Sainte-Anne, Paris, France; Université Paris Cité, Paris, France; Institut Pasteur, Perception and Action Unit, CNRS UMR, 3571, Paris, France.
2 papers in the library · 1 citation · publishing 2026
In patients with treatment-resistant depression receiving esketamine, mystical experiences—similar to those induced by classic psychedelics—occurred in 58% of patients, with high variability across sessions. Higher mean and peak scores on the Mystical Experience Questionnaire (MEQ-30) were associated with greater improvement in depression severity, while dissociative or other non-mystical effects were not. Positive mood and mystical dimensions of the MEQ predicted therapeutic outcomes, and baseline spirituality predicted both treatment response and peak MEQ scores in the first week. These findings suggest that psychedelic-like mystical experiences may contribute to esketamine's therapeutic efficacy.
Regulatory approvals for intranasal esketamine in treatment-resistant depression differ on its indication for suicidal ideation. In a two-center observational study of 261 adults with moderate-to-severe treatment-resistant depression, eight esketamine sessions over four weeks improved both depressive symptoms and suicidal ideation. However, after statistically adjusting for the antidepressant effect, the reduction in suicidal ideation was no longer significant. The findings suggest that esketamine's anti-suicidal effect does not persist independently of its antidepressant effect.