Mystical Experience Induced by Esketamine Treatment: A Real-World Observational Study
This observational study (n=45) followed people with treatment-resistant depression receiving esketamine and found that psychedelic-like mystical experiences were common and varied widely between sessions. Higher mystical experience scores, especially positive mood and mystical feelings, were linked with greater improvement in depression symptoms, while dissociation was not.
Authors
- Mallevays, M.
- Fuet, L.
- Danon, M.
Published
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.
Research Summary of 'Mystical Experience Induced by Esketamine Treatment: A Real-World Observational Study'
Blossom's Take
Mystical experiences (measured with the MEQ) are something that is commonly seen and measured in classical psychedelic studies. This observational study investigated this phenomenon in esketamine administration and found that nearly 60% reported mystical experiences. These experiences also predicted treatment effect (lower depression scores), but the frequency (multiple high MEQ scores) didn't influence outcomes.
Introduction
Treatment-resistant depression is common and difficult to manage, and ketamine and esketamine have emerged as fast-acting antidepressant options. Most attention has focused on dissociation as the main acute subjective effect, but earlier research suggested that this does not reliably explain antidepressant response. At the same time, studies of classic psychedelics have shown that mystical-type experiences, such as feelings of unity, insight, spirituality, bliss, transcendence and ineffability, can be associated with clinical improvement. For (es)ketamine, evidence for similar experiences existed but was limited, inconsistent, and often based on sparse or single-time-point assessments. Mallevays and colleagues aimed to determine whether established psychedelic experience questionnaires can capture esketamine-induced effects in routine care, to describe the frequency and phenomenology of mystical experiences during treatment, and to examine whether these acute subjective effects are associated with antidepressant outcomes. They also explored whether baseline spirituality and personality traits predicted either mystical experiences or treatment response. The study was designed as a real-world, longitudinal observational investigation across the full induction phase of esketamine treatment in patients with treatment-resistant depression.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- APA Citation
Mallevays, M., Fuet, L., Danon, M., Di Lodovico, L., Jaffré, C., Bouzeghoub, L., Mrad, S., Rousselet, A. V., Allary, L., Müh, C., Vissel, B., De Maricourt, P., Vinckier, F., Gaillard, R., Mekaoui, L., Gorwood, P., Petit, A. C., & Berkovitch, L. (2026). Mystical Experience Induced by Esketamine Treatment: A Real-World Observational Study. https://doi.org/10.64898/2026.03.31.26349757
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