The findings, published in Psychological Medicine, come from an experimental study led by Dr. Angharad de Cates of the University of Birmingham in collaboration with researchers at the University of Oxford. The team explored whether a licensed laxative could improve thinking and memory, which are commonly affected in depression and other mental health conditions.

Constipation Drug Tested for Depression Brain Fog

The researchers studied prucalopride, a medication currently approved for chronic constipation. The drug works by activating a specific serotonin receptor (the fourth serotonin receptor, or 5-HT4 R) found in both the gut and the brain. The research was supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre: Oxford Health.

The clinical trial enrolled 50 adults with a history of depression. Participants had previously experienced depressive episodes but had recovered at least six months before joining the study and were not taking medication at the time. They were randomly assigned to receive either 2mg of prucalopride, the standard licensed dose for chronic constipation, or a placebo for between 7-10 days.

Before and after treatment, participants completed a series of tests designed to measure executive function, short and long term memory, and emotional processing. Those who received prucalopride performed better than the placebo group, responding both faster and more accurately on the cognitive assessments.

Dr. Angharad de Cates from the University of Birmingham and corresponding author of the study, said: “Cognitive problems, or brain fog, are an important and often overlooked feature of depression, and can persist even when mood improves. Our study suggests that a targeted serotonin 5-HT4 receptor medication, already used for chronic constipation, may improve cognitive functioning in people with a history of depression.

“These findings support further research into whether 5-HT4-targeting medications can be repurposed for depression, or whether similar drugs could be developed to support people with depression and other mental disorders.”

Memory and Attention Improved

Participants assigned to prucalopride took the medication for five to eight days after titration at the licensed 2mg dose. Researchers reported no significant side effects during the study.

Dr. Angharad de Cates said: “Participants didn’t experience any serious gut complaints, because prucalopride works as a laxative gently stimulating bowel movements.”

The cognitive assessments included:

• an auditory verbal learning and memory task testing declarative memory (AVLT),
• a working memory task (N-back),
• tests of executive functioning (including attention and processing speed: TMT, DSST))

Researchers also used three affective cognition tasks that measured emotional reasoning.

When the results were combined across the “cold” cognitive tests that evaluated memory and executive functioning, participants taking prucalopride achieved higher accuracy (z=+0.59) and faster response times (z=-0.69) than those who received the placebo.

Early Evidence for a New Treatment Approach

Professor Susannah Murphy, Associate Professor at the University of Oxford and senior author of the study said: “For many people, recovery from depression is incomplete because difficulties with memory and concentration persist. 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.”

The research team plans to continue investigating treatments for cognitive problems associated with major depressive disorder. Difficulties with memory, attention, and focus are common among people with depression and can remain long after other symptoms improve. Previous studies have also suggested that 5HT4 receptor agonists may reduce the risk of depression, raising the possibility that this class of drugs could provide multiple mental health benefits.