A Phase II, Open-Label Clinical Trial of Intranasal Ketamine for Depression in Patients with Cancer Receiving Palliative Care (INKeD-PC Study)
Joshua D. Rosenblat, Froukje E. deVries, Zoe Doyle, Roger S. McIntyre, Gary Rodin, Camilla Zimmermann, Ernie Mak, Breffni Hannon, Christian Schulz, Aida Al-Kindy, Zeal Patel, Madeline Li
Cancers January 7, 2023 DOI: 10.3390/cancers15020400 via OpenAlex
Summary
In patients with advanced cancer and major depressive disorder, three flexible doses of intranasal ketamine (50–150 mg) over one week produced rapid antidepressant effects. By day 8, 70% of participants showed a response (depression scores reduced by more than half) and 45% achieved remission. Depression scores dropped from an average of 31 to 11, a decrease of 20 points. Some benefit persisted into the second week without further doses. Side effects were mostly mild and temporary, including fatigue, dissociation, nausea, altered taste, and headaches; one participant withdrew due to a negative dissociative episode. Larger controlled trials are warranted.
Study at a glance
| Characteristics | Single-arm, open-label phase II trial Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Patients with advanced cancer and moderate to severe major depressive disorder |
| Intervention | Intranasal racemic ketamine |
| Dose | 50−150 mg |
| Duration | One-week intervention, with follow-up to day 14 |
| Topics | Depression Ketamine |
| Keywords | Open label Depression economics Nasal administration Palliative care |
| Citations | 49 |
| Key finding | Intranasal ketamine produced high rates of antidepressant response (70%) and remission (45%) by day 8 in patients with advanced cancer and major depressive disorder. |
Abstract
Antidepressants require several weeks for the onset of action, a lag time that may exceed life expectancy in palliative care. Ketamine has demonstrated rapid antidepressant effects, but has been minimally studied in cancer and palliative care populations. Herein, the objective was to determine the feasibility, safety, tolerability and preliminary efficacy of intranasal racemic ketamine for major depressive disorder (MDD) in patients with advanced cancer. We conducted a single-arm, open-label phase II trial at the Princess Margaret Cancer Centre in Toronto, ON, Canada. Participants with advanced cancer with moderate to severe MDD received three flexible doses of intranasal (IN) ketamine (50−150 mg) over a one-week period. The primary efficacy outcome was an antidepressant response and remission rates as determined by the Montgomery−Åsberg Depression Rating Scale (MADRS) from baseline to the Day 8 primary endpoint. Twenty participants were enrolled in the trial, receiving at least one dose of IN ketamine, with fifteen participants receiving all three doses. The Day 8 antidepressant response (MADRS decreased by >50%) and remission (MADRS < 10 on Day 8) rates were high at 70% and 45%, respectively. Mean MADRS scores decreased significantly from baseline (mean MADRS of 31, standard deviation 7.6) to Day 8 (11 +/− 7.4) with an overall decrease of 20 points (p < 0.001). Antidepressant effects were partially sustained in the second week in the absence of additional ketamine doses, with a Day 14 mean MADRS score of 14 +/− 9.9. Common adverse effects included fatigue, dissociation, nausea, dysgeusia and headaches; almost all adverse effects were mild and transient, resolving within 2 h of each ketamine dose with one dropout related to adverse effects (negative dissociative episode). Given these promising findings, larger, controlled trials are merited.