Laxative shows promise for cognitive symptoms of depression

Clinical Takeaway: For patients recovering from depression, consider asking specifically about concentration, memory, and slowed thinking—not just mood. Persistent cognitive symptoms may signal ongoing functional impairment and could become a target for future therapies.

Cognitive dysfunction is a common and often disabling feature of depression. Difficulties with memory, attention, and executive function can persist long after depressive symptoms have resolved and are a major contributor to ongoing functional impairment. More than 40% of patients continue to report cognitive problems even during remission, yet treatment options specifically targeting these symptoms remain limited.

Researchers evaluated whether prucalopride, a selective 5-HT4 receptor agonist currently approved for chronic constipation, could improve cognitive performance in adults with a history of recurrent depression. The study enrolled 50 adults aged 18 to 40 years who'd experienced at least two prior depressive episodes but were currently in remission and not receiving psychiatric medication.

After seven to ten days of treatment, participants receiving prucalopride performed better on tests of memory, working memory, attention, processing speed, and executive function than those receiving placebo. Improvements were seen in both accuracy and response speed across a range of cognitive tasks.

Importantly, cognitive improvements occurred without meaningful changes in mood or anxiety symptoms, suggesting that 5-HT4 receptor stimulation may directly enhance cognition rather than indirectly improving performance through antidepressant effects.

Notably, the benefits were observed on measures of so-called "cold cognition"—the cognitive processes involved in attention, planning, learning, and memory—rather than emotional processing. The findings suggest that 5-HT4 receptor stimulation may represent a novel approach for addressing cognitive dysfunction that persists after recovery from a depressive episode.

No significant adverse effects were reported during the short study period, and participants generally tolerated the medication well.

The results are preliminary, yet they highlight a potential new therapeutic target for one of the most persistent and difficult-to-treat aspects of depression.

“For many people, recovery from depression is incomplete because difficulties with memory and concentration persist,” said senior author Susannah Murphy, PhD, associate professor at the University of Oxford. “This study provides early evidence that 5-HT4 receptor agonists could help restore aspects of cognitive function, opening an exciting new direction for treatment development.”

Source: de Cates AN, et al. 2026 June 15. Psychol Med. Pro-cognitive effects of 5-HT4 receptor agonism in individuals with remitted depression