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

Frontiers in Psychiatry September 2, 2025 DOI: 10.3389/fpsyt.2025.1642025 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Qualitative Peer reviewed
Sample size 43
Population Participants with unipolar depressive disorder
Interventions mindfulness music light-occluding eye mask
Topics Ketamine Meditation Depression Esketamine
Keywords Randomized controlled trial Music therapy Psychotherapist Depression economics Clinical psychology
Citations 1
Registration NCT05168735
Key findings Adding mindfulness, music, and an eye mask to ketamine infusion did not enhance antidepressant effects but enriched the subjective experience for many participants, though a few reported discomfort.

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.

Comparable studies

Other randomized controlled trials on ketamine for depression, most cited first.

Study Year Design Participants
Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode 2013 Randomized controlled trial n = 73
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68

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