Bayesian adaptive randomization trial of intravenous ketamine for veterans with late-life, treatment-resistant depression.
Brittany O'Brien, Charles E Green, Rayan Al-Jurdi, Lee Chang, Marijn Lijffijt, Sidra Iqbal, Tabish Iqbal, Alan C Swann, Sanjay J Mathew
Contemporary clinical trials communications December 1, 2019 DOI: 10.1016/j.conctc.2019.100432 via PubMed
Summary
AI-generated from the abstractOver eleven million U.S. Veterans are 65 or older, and nearly 20% of that group experiences clinically significant depression. Existing medications often work poorly for late-life depression, especially when it is treatment-resistant. Ketamine offers a potentially rapid-acting option, but few studies have tested it in older adults. This ongoing trial uses an adaptive randomization design to compare the safety, tolerability, efficacy, and durability of three different low doses of intravenous ketamine against a single dose of an active placebo (midazolam) in older depressed veterans. As the study proceeds, Bayesian adaptive randomization shifts the odds of assignment toward the more promising dose conditions.
Study at a glance
| Characteristics | Adaptive randomization trial Peer reviewed |
|---|---|
| Population | Older depressed veterans with late-life treatment-resistant depression |
| Interventions | Ketamine Midazolam |
| Topics | Depression Ketamine |
| Keywords | Adaptive design Bayesian trial design Late-life depression |
| Citations | 10 |
| Key finding | The study is ongoing; results are expected to inform the viability of ketamine treatment and optimal dosing strategies for patients with late-life treatment-resistant depression. |
Abstract
More than eleven million U.S. Veterans are at least 65 years of age, an age group of which almost 20% suffers from clinically significant depressive symptoms. Available pharmacological treatments are suboptimal for patients, including veterans, with late-life depression. Ketamine has emerged as a potentially promising rapid-acting therapy for treatment-resistant depression (TRD). However, few studies have examined the safety, tolerability and efficacy of ketamine therapy for older adults with late-life TRD (LL-TRD). This study uses an adaptive randomization design to test the safety, tolerability, efficacy, and durability of three distinct, single sub-anesthetic doses of intravenous (IV) ketamine versus a single dose of active placebo (midazolam) in older depressed veterans. As the study progresses, Bayesian adaptive randomization recalibrates randomization ratios to allocate more participants to conditions demonstrating greater promise and fewer participants to conditions with less promise. Secondary analyses explore clinical and biological moderating and mediating factors of rapid treatment response. Results are expected to inform both the viability of ketamine treatment and optimal dosing strategies for patients with LL-TRD.