Mindfulness, Music, and Visual Occlusion in Ketamine Therapy for Depression: Do They Change Outcomes? A Qualitative and Quantitative Analysis of a Randomized Controlled Trial

Mina Kheirkhah^1,2Nastasia McDonald³Julia Aepfelbacher³Manivel Rengasamy³Sharvari Shivanekar³Crystal Spotts³Iya Cooper³Andrew Baumeister³Elizabeth Bell³Kevin Do-Nguyen³Mary L. Woody³Shabnam Hossein³Ioline Henter¹Allison Carol Nugent⁴Nadia S. Hejazi¹Hamidreza Jamalabadi⁵Mani Yavi¹Martin Walter²Carlos A. Zarate¹Rebecca B. Price^3*

• ¹Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States
• ²Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany
• ³Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States
• ⁴Magnetoencephalography Core, National Institute of Mental Health, Bethesda, MD, United States
• ⁵Department of Psychiatry and Psychotherapy, Philipps University of Marburg, Marburg, Germany

ABSTRACT Introduction: This is the first randomized controlled trial to use both qualitative and quantitative methods to evaluate the effects of a combined sensory intervention that included mindfulness, music, and a light-occluding eye mask during antidepressant-dose ketamine treatment for depression. Methods: Forty-three participants with unipolar depressive disorder enrolled in the study; 22 individuals were randomly assigned to receive mindfulness, music, and eye mask during ketamine infusion, and 21 individuals in the control group received only ketamine without additional interventions. Quantitative analyses assessed the impact of combined sensory intervention on ketamine's antidepressant effects, and qualitative analyses explored the participants' experiences. Results: Depression scores improved significantly and similarly across both groups. However, adding combined sensory interventions to ketamine infusion enriched subjective experience. More participants in the combined sensory intervention group reported deeper engagement, a stronger sense of connection to reality, increased focus on the experience rather than the strangeness of it, moments of relief from sadness, and feelings of awe and spiritual insight compared to the control group. Four individuals in the combined sensory intervention group also reported discomfort. Discussion: Ketamine's antidepressant effects remained consistent with or without combined sensory intervention; however, mindfulness, music, and eye mask made the experience more meaningful and emotionally rich for many, though it also introduced discomfort for a few—this outcome might be avoided by making these interventions optional. Given the limited research on