People suffering from depression often continue to experience memory problems, difficulty concentrating, and mental “brain fog” even after they feel better. Researchers now say that existing prescription drugs currently approved to treat chronic constipation may also help improve lingering cognitive symptoms.
The survey results are psychiatryfrom an experimental study led by Dr Angharad de Kates from the University of Birmingham in collaboration with researchers from the University of Oxford. The research team investigated whether approved laxatives could improve thinking and memory, which are commonly affected in depression and other mental health conditions.
Laxative drug to treat brain fog in depression tested
The researchers studied prucalopride, which is currently approved to treat chronic constipation. This drug works by activating a specific serotonin receptor (the fourth serotonin receptor, or 5-HT4 R) located in both the gut and brain. This research was supported by the National Institute for Health and Care Excellence (NIHR) Biomedical Research Center, Oxford Health.
The clinical trial involved 50 adults with a history of depression. Participants had previously experienced a depressive episode but had been in recovery for at least 6 months before participating in the study and were not taking any medication at the time. They were randomly assigned to receive either 2 mg of prucalopride, the standard approved dose for chronic constipation, or a placebo for 7 to 10 days.
Before and after treatment, participants completed a battery of tests designed to measure executive function, short- and long-term memory, and emotional processing. The group receiving prucalopride performed better than the placebo group, responding faster and more accurately on cognitive assessments.
“Cognitive problems, or brain fog, are an important but often overlooked feature of depression and can persist even when mood improves. Our study suggests that targeted serotonin 5-HT4 receptor drugs, already used for chronic constipation, may improve cognitive function in people with a history of depression,” said Dr. Angharad de Cates, from the University of Birmingham and corresponding author of the study.
“These findings support further research into whether drugs targeting 5-HT4 can be repurposed for depression, or whether similar drugs can be developed to support people with depression and other mental disorders.”
Improving memory and attention
Participants assigned prucalopride took the drug for 5 to 8 days after titrating to the approved 2 mg dose. Researchers reported no serious side effects during the study.
Dr. Angharad de Kates said, “Prucalopride acts as a laxative that gently stimulates bowel movements, so the participants did not experience any serious intestinal upset.”
Cognitive assessments include:
- Auditory Verbal Learning and Memory Task Test Declarative Memory (AVLT),
- working memory task (N-back),
- Tests of executive function (including attention and processing speed: TMT, DSST)
The researchers also used three emotional cognition tasks that measure emotional reasoning.
Combined with the results of “cold” cognitive tests assessing memory and executive function, participants who took prucalopride achieved higher accuracy (z=+0.59) and faster reaction times (z=-0.69) than those who took a placebo.
Early evidence of new therapeutic approaches
Professor Susannah Murphy, Associate Professor at the University of Oxford and lead author of the study, said: “For many people, recovery from depression is incomplete as memory and concentration continue to decline. This study provides early evidence that 5-HT4 receptor agonists may help restore aspects of cognitive function, opening exciting new directions for treatment development.”
The research team plans to continue investigating treatments for cognitive problems associated with major depressive disorder. Decreased memory, attention, and concentration are common in people with depression and can persist long after other symptoms have improved. Previous research has also suggested that 5HT4 receptor agonists may reduce the risk of depression, raising the possibility that this class of drugs may offer multiple mental health benefits.
