A selective serotonin 4 (5-HT4) receptor agonist approved for chronic constipation improved persistent cognitive symptoms in individuals with remitted major depressive disorder (MDD). Results of the small, double-blind, placebo-controlled, proof-of-concept study showed that participants who received prucalopride performed significantly better than those who received placebo, with gains observed across multiple objective measures of nonemotional (cold) cognition.