Intranasal ketamine and existential distress in advanced cancer: secondary trial results

The question

Beyond easing depression, can intranasal ketamine also reduce existential distress, anxiety and other symptoms in people with advanced cancer receiving palliative care?

What they did

The researchers looked again at data from the INKeD-PC trial, which tested racemic ketamine given as a nasal spray to patients with cancer in palliative care. This report covers 15 participants who received 3 doses and completed the main assessment point. Alongside the main depression scale (the Montgomery-Asberg Depression Rating Scale), participants completed questionnaires on depression, anxiety, general symptoms, quality of life, and distress about death and dying. Written comments from participants were used to help interpret the scores.

What they found

Scores improved on every secondary measure, and the size of the change passed the thresholds usually considered clinically meaningful. The improvements were large in statistical terms: anxiety (effect size d = 1.22, P = 0.004), death and dying distress (d = 0.91, P = 0.003), general symptom burden (d = 1.21, P = 0.003) and quality of life (d = 1.53, P = 0.004). The existential well-being part of the quality-of-life questionnaire also improved (d = 1.02, P = 0.015). Changes in depression scores were not significantly correlated with changes in the other measures, and psychological symptoms improved more than physical ones.

The fine print

Only 15 people were included, and this was a secondary analysis of outcomes the trial was not designed to test first. The abstract does not describe a placebo comparison for these results, so improvement over time, hope and attention from the study team could all contribute. Follow-up appears limited to the primary endpoint, so it is unclear how long any benefit lasted. This summary is based on the abstract alone.

What it means

In a small group of people with advanced cancer being treated for depression, ketamine was associated with improvements in anxiety, quality of life and distress about dying, but the study is too small and too preliminary to show that ketamine caused these changes.

Evidence grade: Very low. This is a secondary analysis of only 15 people from a small trial, with no comparison group reported for these outcomes.

This summary is based on the study’s published abstract.