Research indicates that prucalopride, a drug for constipation, may help improve cognitive function in individuals with a history of depression.
New Delhi, India Jul 16, 2026 ALN: People struggling with depression often continue to experience memory problems, poor concentration, and mental "brain fog" even after their mood improves. This phenomenon highlights the complexity of depression as a mental disorder, where emotional symptoms can sometimes overshadow cognitive impairments. Now, researchers say an existing prescription drug approved to treat chronic constipation may also help improve those lingering cognitive symptoms, offering a glimmer of hope for those affected by the cognitive aspects of depression.
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 conditions. This research not only sheds light on the potential for repurposing existing medications but also emphasizes the need for a holistic approach to treating depression, which includes addressing cognitive dysfunction.
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. This dual action is particularly intriguing, as it suggests that gut may play a significant role in mental , a connection that is gaining traction in recent years. The research was supported by the National Institute for and Care Research (NIHR) Biomedical Research Centre: Oxford, which underscores the importance of funding for innovative studies that explore new uses for existing medications.
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. This selection criterion was crucial to ensure that the effects observed were due to prucalopride and not influenced by other antidepressants. 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. Randomized controlled trials are considered the gold standard in clinical research, as they minimize bias and allow for a clear comparison between treatment and control groups.
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. This improvement in cognitive performance suggests that prucalopride may have a significant impact on cognitive domains often impaired in individuals with depression, thereby addressing a critical gap in current treatment options.
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." This statement emphasizes the need for further investigation into how existing medications can be adapted to treat complex symptoms associated with mental disorders.
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. The implications of this research could be far-reaching, potentially leading to new treatment protocols that incorporate cognitive enhancement strategies alongside traditional mood-stabilizing therapies.
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, which is particularly noteworthy considering the potential for adverse effects with many psychotropic medications. Dr. Angharad de Cates noted: "Participants didn't experience any serious gut complaints, because prucalopride works as a laxative gently stimulating bowel movements." This points to the favorable safety profile of prucalopride, making it a candidate for further study in the context of cognitive enhancement in depression.
The cognitive assessments included:
Researchers also used three affective cognition tasks that measured emotional reasoning. These diverse assessments provided a comprehensive overview of cognitive functioning, allowing researchers to capture various dimensions of memory and attention that are often impacted in depression.
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. This quantitative data adds weight to the argument that prucalopride may offer cognitive benefits that could significantly improve the quality of life for individuals recovering from depression.
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." This statement reflects a growing recognition of the need to address cognitive deficits in the treatment of depression, which have often been sidelined in favor of more immediate mood-related symptoms.
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 benefits. Such findings could pave the way for a new era in the treatment of depression, where cognitive enhancement becomes a standard part of therapeutic protocols.
In conclusion, this study opens the door to further exploration of the role that gut-brain interactions may play in mental , particularly in relation to cognitive deficits associated with depression. As researchers continue to investigate the potential of prucalopride and similar medications, there is hope that new, effective treatments will emerge that not only alleviate mood symptoms but also enhance cognitive functioning, thereby improving overall quality of life for individuals suffering from depression.
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