Protocol and pilot results for a double-blind randomized placebo-controlled trial of ketamine under propofol sedation for chronic pain and depression.
Theresa R. Lii, Pilleriin Sikka, Ben Deverett, O. Altirkawi, Boris D. Heifets
Pain Management April 16, 2026 DOI: 10.1080/17581869.2026.2658080 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Clinical protocol Randomized Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 42 |
| Population | Adults with chronic pain and comorbid depression |
| Interventions | Ketamine Propofol sedation Placebo (saline) |
| Dose | 0.5 mg/kg |
| Duration | 40-minute infusion plus 40 minutes post-infusion |
| Measures | 0-10 Numeric Rating Scale |
| Topics | Depression Esketamine Ketamine |
| Registration | NCT06317636 |
| Key points | The protocol proposes that propofol sedation spanning ketamine infusion may reduce expectancy bias by masking ketamine's acute dissociative effects. Among six pilot participants, procedures were completed without serious adverse events; 5 of 6 guessed ketamine immediately post-sedation, but only 2 of 6 correctly identified allocation at later assessments, and expectancy and confidence ratings varied widely without favoring either treatment. |
Abstract
Introduction: Ketamine shows promise for treatment-refractory chronic pain and depression, but randomized trials risk unblinding from ketamine's acute dissociative effects. Propofol sedation may mitigate this, though it has not been prospectively tested as a masking strategy outside of surgical contexts.
Methods: This protocol describes a single-center, randomized, double-blind, placebo-controlled, parallel-group superiority trial enrolling 42 adults (including 6 pilot participants) with chronic pain and comorbid depression. Intravenous ketamine (0.5 mg/kg) or placebo (saline) will be administered under propofol sedation spanning the 40-minute infusion and 40 minutes post-infusion. The primary outcome is change in mean daily pain intensity (0-10 Numeric Rating Scale), assuming a detectable difference of 1.5 points. Secondary outcomes include depression severity and blinding measures. FEASIBILITY RESULTS Six pilot participants completed procedures without serious adverse events. While 5/6 guessed ketamine immediately post-sedation, only 2/6 correctly identified allocation at subsequent assessments. Expectancy and confidence ratings varied widely without favoring either treatment.
Discussion: Propofol-enhanced masking may reduce expectancy bias and improve interpretability for ketamine trials. Pilot results suggest propofol sedation can be used safely and effectively as a blinding tool, offering a framework for studying other psychoactive therapeutics. CLINICAL TRIAL REGISTRATION www.clinicaltrials.gov identifier is NCT06317636.