This qualitative interview study (n=17) of those receiving esketamine (35-210mg/70kg, 12x over 6w) for depression explores patients' experiences. Findings reveal highly variable effects of ketamine with common psychological distress, and central themes include perceptual effects, detachment, stillness and openness, mystical-type effects, fear and anxiety, feeling hungover and tired, and a neutralizing mood effect post-session. While patients reported several esketamine effects with psychotherapeutic potential such as increased openness, detachment, and mystical-type experiences, the study identifies a need for additional support due to the frequency and severity of the perceived distress during the treatment.
Background
Ketamine and its enantiomers are widely researched and increasingly used to treat mental disorders, especially treatment-resistant depression. The phenomenology of ketamine-induced experiences and their relation to its psychotherapeutic potential have not yet been systematically investigated.
Aims
To describe the phenomenology of patient experiences during oral esketamine treatment for treatment-resistant depression (TRD) and to explore the potential therapeutic relevance of these experiences.
Methods
In-depth interviews were conducted with 17 patients after a 6-week, twice-weekly ‘off label’ generic oral esketamine (0.5-3.0mg/kg) treatment program. Interviews explored participants’ perspectives, expectations, and experiences with oral esketamine treatment. Audio interviews were transcribed and analyzed using an Interpretative Phenomenological Analysis (IPA) framework.
Results
The effects of ketamine were highly variable, and psychological distress was common in most patients. Key themes included (a) perceptual effects (auditory, visual, proprioceptive), (b) detachment (from body, self, emotions, and the world), (c) stillness and openness, (d) mystical-type effects (transcendence, relativeness, spirituality), and (e) fear and anxiety. Key themes related to post-session reports included (a) feeling hungover and fatigued, and (b) lifting the blanket: neutralizing mood effects.
Conclusion
Patients reported several esketamine effects with psychotherapeutic potential, such as increased openness, detachment, an interruption of negativity, and mystical-type experiences. These experiences deserve to be explored further to enhance treatment outcomes in patients with TRD. Given the frequency and severity of the perceived distress, we identify a need for additional support in all stages of esketamine treatment.
Papers in Blossom that reference this study
Samalin, L., Rothärmel, M., Mekaoui, L. et al. · Journal of Psychiatric Research (2026)
Mathai, D. S., Hilbert, S., Sepeda, N. D. et al. · Psychedelic Medicine (2023)
Pepe, M., Bartolucci, G., Marcelli, I. et al. · Brain Sciences (2023)