A new study published in the Journal of Psychological Medicine looked at whether the drug, Prucalopride, may have potential as a way to improve cognition in depression.
Prucalopride is usually prescribed to adults to relieve chronic constipation. It’s often prescribed when other laxatives have not worked.
“In people with remitted depression, we investigated whether seven to ten days of Prucalopride, a licensed treatment for constipation that selectively targets the 5-HT4 receptor, could improve cognition,” study author Angharad N. de Cates told us. “We were particularly interested in whether it might help with the cognitive difficulties that are common in depression and can persist even after mood symptoms have improved.”
The 5-HT4 receptor controls memory and learning in the brain. Previous studies in healthy volunteers suggested that Prucalopride might have pro-cognitive effects, so the researchers expected it might improve performance on cognitive tasks. The research team also thought the effects would be greater for non-emotional (also known as “cold”) cognition than for emotional processing.
“Cognitive problems are common in depression, and are often not well treated by standard antidepressants, and can affect daily functioning and long-term recovery,” de Cates told us. “Earlier preclinical and human studies suggested that 5-HT4 receptor agonism could enhance memory and attention, but this had not yet been tested in people with remitted depression.”
The researchers randomized 50 people with a history of at least two episodes of depression to receive either Prucalopride or a placebo for seven to ten days. Participants completed a battery of cognitive tasks at baseline and after treatment, covering declarative memory, working memory, executive functioning, and also emotional processing.
“Prucalopride improved performance on several measures of ‘cold’ cognition,” de Cates told us. “Compared with the placebo, participants were more accurate on the auditory verbal learning task and faster on the working memory task, and the composite analysis across the ‘cold’ tasks suggested benefits for both accuracy and speed. We did not find evidence that these cognitive effects were related to changes in mood, and Prucalopride did not appear to have a meaningful effect on emotional processing.”
The findings were broadly in line with what the research team expected. They did not see a clear effect on emotional processing, which is similar to what has been seen in healthy volunteers and suggests Prucalopride may work differently from conventional antidepressants such as Selective Serotonin Reuptake Inhibitors (SSRIs).
“This is the first study to test 5-HT4 receptor agonism in people with previous depression,” de Cates told us. “The results suggest that Prucalopride may have potential as a way to improve cognition in depression. They also provide a strong basis for further studies of 5-HT4 receptor agonists in depression and other mental disorders where cognitive problems are common, such as psychosis.”
The researchers are encouraged by the consistency of the findings across different cognitive measures and studies, and by the possibility that drugs like Prucalopride could eventually be repurposed to help people with cognitive symptoms in mental illness.
