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. 2025 Sep 2:16:1642025.
doi: 10.3389/fpsyt.2025.1642025. eCollection 2025.

Mindfulness, music, visual occlusion in ketamine therapy for depression: do they change outcomes? A qualitative and quantitative analysis of a randomized controlled trial

Mina Kheirkhah  1   2 , Nastasia McDonald  3 , Julia Aepfelbacher  3 , Manivel L Rengasamy  3 , Sharvari Shivanekar  3 , Crystal Spotts  3 , Iya Cooper  3 , Andrew Baumeister  3 , Elizabeth Bell  3 , Kevin Do-Nguyen  3 , Mary L Woody  3 , Shabnam Hossein  3 , Ioline D Henter  1 , Allison C Nugent  4 , Nadia S Hejazi  1 , Hamidreza Jamalabadi  5 , Mani Yavi  1 , Martin Walter  2 , Carlos A Zarate Jr  1 , Rebecca B Price  3
Affiliations

Mindfulness, music, visual occlusion in ketamine therapy for depression: do they change outcomes? A qualitative and quantitative analysis of a randomized controlled trial

Mina Kheirkhah et al. Front Psychiatry. .

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 combining ketamine with sensory interventions, these results contribute valuable insights and underscore the need for further studies to explore this combined therapeutic approach.

Clinical trial registration: https://clinicaltrials.gov/study/NCT05168735, identifier NCT05168735.

Keywords: depression; depression rating scales; eye mask; ketamine; mindfulness; music; qualitative analyses; quantitative analyses.

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Conflict of interest statement

Author CZ is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; as a co-inventor on a patent for the use of 2R,6Rhydroxynorketamine, S-dehydronorketamine, and other stereoisomeric dehydroxylated and hydroxylated metabolites of R,S-ketamine metabolites in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of 2R,6Rhydroxynorketamine and 2S,6S-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders. He has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. RP is the named inventor on a University of Pittsburgh-owned patent filing related to a biobehavioral treatment combination involving the administration of rapid acting medications such as ketamine. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
MADRS score (primary outcome measure) and secondary outcome measures (HAM-D, QIDS, MAAS, PTQ, and DSES) in participants who received the mindfulness, music, and eye mask intervention during ketamine infusion compared to controls who received only ketamine without any additional interventions. Scores for six different scales are illustrated for participants who received ketamine plus mindfulness, music, and eye mask (combined sensory intervention, red) or controls (blue) at pre-infusion baseline and at five different timepoints post-ketamine infusion. No significant differences were found between individuals in the combined sensory intervention group and the control group. MADRS, Montgomery-Asberg Depression Rating Scale; HAM-D, Hamilton Depression Rating Scale; QIDS, Quick Inventory of Depressive Symptomatology; MAAS, Mindful Attention Awareness Scale; DSES, Daily Spiritual Experience Scale; PTQ, Perseverative Thinking Questionnaire.
Figure 2
Figure 2
Boxplot representation of Montgomery-Asberg Depression Rating Scale (MADRS) (primary outcome measure) and Hamilton Depression Rating Scale (HAM-D) (secondary outcome measure) scores for participants who received ketamine plus mindfulness, music, and eye mask (combined sensory intervention, red, left plots) or controls who received only ketamine without any additional interventions (blue, right plots) across pre-infusion baseline and five post-ketamine timepoints. The boxplots demonstrate a significant decrease in both MADRS and HAM-D scores at each of the five post-infusion timepoints compared to the pre-infusion baseline in both groups. Statistical significances (after Bonferroni correction) are denoted by asterisks: ***p < 0.001; *p<0.05.
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