A single low-dose infusion of ketamine in older military veterans with treatment-resistant depression temporarily increases the brain's neural complexity, measured by electroencephalogram (EEG) markers Lempel-Ziv complexity and multiscale entropy, within 30 minutes after infusion. These effects vary over time, with some complexity measures decreasing later. However, these changes in complexity were not linked to reductions in depressive symptoms after seven days. The findings suggest that ketamine produces broad, time-varying effects on brain dynamics beyond previously studied gamma oscillations, offering a potential non-linear marker of the drug's action.
Over 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.