Mystical Experience Induced by Esketamine Treatment: A Real-World Observational Study

Area of Science:

• Psychiatry
• Neuroscience
• Psychopharmacology

Background:

• Esketamine is a rapid-acting antidepressant with psychoactive effects.
• Dissociative effects are common but their therapeutic relevance is unclear.
• Psychedelic-like mystical experiences induced by esketamine are poorly understood.

Purpose of the Study:

• To characterize esketamine-induced mystical experiences.
• To investigate the relationship between mystical experiences and clinical outcomes in treatment-resistant depression.
• To explore the role of baseline spirituality in treatment response.

Main Methods:

• Longitudinal observational study of 45 patients receiving esketamine for treatment-resistant depression.
• Systematic measurement of acute subjective effects using the Mystical Experience Questionnaire (MEQ-30) and other scales.
• Principal Component Analysis (PCA) to validate MEQ-30 for esketamine effects.

Main Results:

• Mystical experiences (MEQ-30 score ≥ 60) occurred in 58% of patients, showing significant variability.
• Higher mean and peak MEQ scores were associated with greater improvement in depression symptoms (Montgomery-Åsberg Depression Rating Scale).
• Dissociative effects did not correlate with therapeutic efficacy; positive mood and mystical dimensions predicted outcomes. Baseline spirituality predicted outcomes and MEQ scores.

Conclusions:

• Psychedelic-like mystical experiences, not dissociation, are linked to esketamine's therapeutic efficacy.
• These findings support the role of mystical experiences in antidepressant treatment, extending beyond classic psychedelics.
• Individual spirituality may influence both the experience and effectiveness of esketamine therapy.