Intranasal Ketamine for Existential Distress in Advanced Cancer.
Stefan Aguiar, Mary Makarious, Orly Lipsitz, Froukje E Devries, Zoe Doyle, Roger S McIntyre, Gary Rodin, Camilla Zimmermann, Ernie Mak, Breffni Hannon, Christian Schulz-Quach, Aida Al Kindy, Zeal Patel, Joshua D Rosenblat, Madeline Li
Journal of pain and symptom management August 1, 2026 Peer reviewed DOI: 10.1016/j.jpainsymman.2026.04.611 via PubMed
Summary
Intranasal ketamine treatment led to clinically meaningful improvements in existential distress among 15 patients with advanced cancer receiving palliative care. Participants received three doses of ketamine and showed significant enhancements in various measures, including anxiety and quality of life, surpassing minimal clinically important differences. Notably, psychological symptoms improved more than physical ones. However, correlations between depression scores and secondary outcomes were not significant.
Study at a glance
| Design | randomized controlled trial |
|---|---|
| Sample size | 15 |
| Population | patients with advanced cancer receiving palliative care |
| Key finding | Intranasal ketamine was associated with clinically meaningful improvements in existential distress in individuals with advanced cancer being treated for depression. |
Abstract
Depression and existential distress are highly prevalent among patients with advanced cancer, and there is growing evidence for ketamine as a rapidly acting antidepressant in the population, but few studies have examined existential distress outcomes with ketamine treatment. The INKeD-PC trial demonstrated efficacy of intranasal racemic ketamine for depression in patients with cancer receiving palliative care. We now report on secondary trial outcomes, including those related to existential distress. This analysis is based on 15 trial participants who received 3 doses of ketamine and completed the primary endpoint measures, including Montgomery-Åsberg Depression Rating Scale as primary outcome, as well as the Patient Health Questionnaire-9 for depression, Generalized Anxiety Disorders-7, Edmonton Symptom Assessment System-Revised, McGill Quality of Life Questionnaire (MQOL), and the Death and Dying Distress Scale. Qualitative comments from participants were used to support quantitative findings. Improvements were observed across all secondary outcome measures, exceeding established minimal clinically important differences. Were as follows: Generalized Anxiety Disorders-7 (d = 1.22, P= 0.004), Death and Dying Distress Scale (d=0.91, P=0.003), Edmonton Symptom Assessment System-Revised (d = 1.21, P= 0.003) and McGill Quality of Life Questionnaire (d = 1.53, P= 0.004). Correlations between changes in Montgomery-Åsberg Depression Rating Scale and secondary outcomes were not significant, and subscales related to psychological symptoms improved more than physical symptoms, including the MQOL Existential Well-Being factor (d=1.02, P=0.015). Intranasal ketamine was associated with clinically meaningful improvements in existential distress in individuals with advanced cancer being treated for depression. Ketamine may have relevance as a single agent for multidimensional distress in palliative care.