Constipation drug shows early promise for depression-related brain fog

A licensed constipation medicine improved performance on thinking tests in a small trial of adults who had recovered from depression, according to University of Birmingham researchers. The findings matter because memory problems, poor concentration and slower thinking can continue after mood symptoms have eased.

The study, published in Psychological Medicine, tested prucalopride, a prescription drug approved for chronic constipation. Researchers from the University of Birmingham and the University of Oxford examined whether a medicine that acts on a serotonin receptor found in the gut and brain could help with cognitive symptoms linked to depression.

The trial enrolled 50 adults with a history of depression, the University of Birmingham said. Participants had recovered at least six months before joining the study and were not taking medication at the time.

Researchers randomly assigned participants to receive either prucalopride or a placebo. The prucalopride group received 2mg, the standard licensed dose for chronic constipation, over a treatment period of seven to 10 days, with five to eight days at the licensed dose after titration.

Before and after treatment, participants completed tests covering executive function, short- and long-term memory, attention, processing speed and emotional processing. The University of Birmingham said people who took prucalopride responded more quickly and more accurately than those given placebo on cognitive assessments.

The drug targets the 5-HT4 serotonin receptor, also called the fourth serotonin receptor. The research team said that receptor is present in both the digestive system and the brain, making it a potential target for treatments aimed at cognition as well as bowel function.

Dr. Angharad de Cates of the University of Birmingham, the study’s corresponding author, said cognitive problems are an often missed part of depression and can remain after mood improves. She said the results suggest a 5-HT4 receptor medicine already used for constipation may improve cognition in people with a depression history.

The tests included an auditory verbal learning and memory task, known as AVLT; a working memory task, known as N-back; and executive-function tests including TMT and DSST, according to the University of Birmingham. Researchers also used three tasks designed to measure affective cognition, or emotional reasoning.

When the researchers combined results from the non-emotional cognition tests, the prucalopride group showed higher accuracy and faster response times than the placebo group. The reported standardized scores were z=+0.59 for accuracy and z=-0.69 for response time.

The University of Birmingham said researchers found no significant side effects during the study. De Cates said participants did not report serious gut complaints, noting that prucalopride works by gently stimulating bowel movements.

Professor Susannah Murphy of the University of Oxford, the study’s senior author, said many people have an incomplete recovery from depression because memory and concentration difficulties persist. She said the findings offer early evidence that 5-HT4 receptor agonists could help restore parts of cognitive function.

The research was supported by the National Institute for Health and Care Research Biomedical Research Centre: Oxford Health. The team said it plans to continue studying treatments for cognitive problems associated with major depressive disorder.

The researchers also noted that earlier studies have suggested 5-HT4 receptor agonists may reduce depression risk. They said further work is needed to assess whether prucalopride or related drugs could be repurposed for depression-related cognitive symptoms or developed for other mental health conditions.

This story draws on original reporting from ScienceDaily.