Mystical Experience Induced by Esketamine Treatment: A Real-World Observational Study
Maia Mallevays, Louise Fuet, Michel Danon, Laura Di Lodovico, Claire Jaffré, Louise Bouzeghoub, Seifeddine Mrad, Anne-Victoire Rousselet, Lola Allary, Chlöé Müh, Bente Vissel, Pierre De Maricourt, Fabien Vinckier, Raphaël Gaillard, Lila Mekaoui, Philip Gorwood, Anne-Cécile Petit, Lucie Berkovitch
medRxiv Preprint Server March 31, 2026 preprint DOI: 10.64898/2026.03.31.26349757 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Longitudinal |
|---|---|
| Sample size | 45 |
| Population | Patients receiving esketamine for treatment-resistant depression |
| Intervention | Esketamine |
| Duration | Induction phase of esketamine treatment |
| Topics | Esketamine Mystical experience |
| Citations | 1 |
| Key findings | Mystical experiences during esketamine treatment, measured by the MEQ-30, were associated with greater improvement in depression severity, while dissociative effects were not. |
Abstract
Esketamine is a fast-acting antidepressant drug which induces acute psychoactive effects. The most frequent is a dissociative state which seems unrelated to therapeutic efficacy. Other esketamine-induced effects, including psychedelic-like mystical experiences, have been poorly studied in terms of phenomenology and frequency, and may carry specific therapeutic relevance. In this study, we characterised esketamine-induced mystical experiences in relation with clinical outcomes. We conducted a longitudinal observational study and systematically measured acute subjective effects in patients receiving esketamine for treatment-resistant depression after each administration across the induction phase. A total of 45 patients were included, from two independent centres, totalling 352 esketamine administrations. Principal Component Analysis (PCA) supported the validity of the Mystical Experience Questionnaire (MEQ-30) for assessing esketamine-induced subjective effects, with components recovering dimensions previously validated with classic psychedelics. Mystical experiences (MEQ-30 score ≥ 60) occurred in 58% of patients, with high inter- and intra-individual variability in frequency, intensity, and phenomenology across sessions. Higher mean and peak MEQ scores were associated with greater improvement in Montgomery-Åsberg Depression Rating Scale scores from pre- to post-treatment, whereas the intensity of dissociative or other non-mystical effects was not. Positive mood and mystical MEQ dimensions in particular predicted therapeutic outcomes. Baseline spirituality also significantly predicted treatment outcomes and peak MEQ scores in the first week of treatment. These findings add to the growing body of evidence suggesting that psychedelic-like mystical experiences may be associated to therapeutic efficacy, not only in classic psychedelic-assisted therapy, but also in esketamine treatment.
Comparable studies
Other observational and cohort studies on esketamine, most cited first.
Citations in the library
Cited by 2
- Reply to ‘Methodological concerns and interpretative limitations of assessing subjective effects of ketamine’ npj Mental Health Research September 22, 2026
- Preliminary Non-Randomized Clinical Trial of Subcutaneous Esketamine in Treatment-Resistant Depression: Exploring Adjunctive Effects of Ketamine-Assisted Psychotherapy medRxiv Preprint Server May 31, 2026