June 19, 2026, 11:37 am | Read time: 4 minutes
Not only frees the gut but apparently also the soul: A medication originally used for constipation alleviates cognitive depression symptoms after just one week. These are symptoms that often persist after recovery. FITBOOK spoke with study leader Prof. Angharad de Cates about the background and the hopes that those affected can now have.
It often happens that certain side effects of some medications turn out to be a blessing. This is also the case with prucalopride, a drug used to treat chronic constipation. It helps with ailments that become particularly noticeable when the depression itself has been overcome. These include lack of concentration, poor memory, or a foggy feeling when thinking (brain fog). These so-called cognitive residual symptoms can make returning to everyday life difficult. Prucalopride, an already approved and cost-effective medication, offers hope of finally getting rid of these burdensome depression symptoms. The study results were recently published in the journal “Psychological Medicine.”1
How a Medication for Constipation Can Help with Depression Symptoms, According to the Study Leader
Prucalopride activates the 5-HT4 receptor, a docking site for the “satisfaction neurotransmitter” serotonin. “We believe that activating the 5-HT4 receptor strengthens brain networks that are crucial for learning and memory. The active ingredient could help nerve cells communicate better with each other and process information more efficiently,” explains study leader Prof. Angharad de Cates in response to a query from FITBOOK. Previous studies in mice had shown that activating this receptor could support neuroplasticity. If depression impairs certain thought processes, the assumption is that targeted influence could help strengthen mental performance again. De Cates and a research team from Oxford University and the University of Birmingham have now pursued this question in humans.
Active Ingredient Administered to 50 Adults with Resolved Depression
For the study, 50 patients (ages 18 to 40) who had previously experienced depressive episodes were recruited. It was crucial that the depression had already subsided. Participants were randomly given either two milligrams of prucalopride, a dose currently approved only for chronic constipation, or a placebo for seven to ten days. Before and after taking the medication, each participant completed a series of cognitive tests, including:
- Memory
- Working memory
- Attention
- Processing speed
- Emotional perception
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Surprising Results
The prucalopride group was able to reliably remember previously heard words compared to the placebo group after taking the medication. This suggests that the active ingredient could improve the ability to absorb and recall new information. The prucalopride group also responded significantly faster in a task that required retaining information in memory while simultaneously tracking new information. Particularly surprising: Prucalopride apparently helped to more accurately recognize emotions (such as fear, joy, anger, or surprise) in faces that were visible for only half a second. Overall, the individuals who received prucalopride performed significantly better on several cognitive tests than the placebo group.
According to de Cates, there were no significant side effects: “Prucalopride was well tolerated in our study. There were no significant digestive side effects in people without constipation compared to placebo, apart from a sign of reduced appetite.”
Researcher Speaks of Long-Underestimated Problem
For those who have overcome depression but still feel mentally slowed down, there are currently no approved therapies. “About 40 percent suffer from concentration difficulties, forgetfulness, and poor word memory despite improved mood,” says de Cates. “They continue to suffer, which has been underestimated so far. Since conventional antidepressants do not always sufficiently improve these problems, we need new approaches that specifically support mental performance.”
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Is Hope in Sight?
Unfortunately, the study is too small and the study period too short. It is not conclusive enough to use the medication for the mentioned depression symptoms just yet. De Cates remains cautiously optimistic: “Our results offer potential for treating cognitive problems in depression. But we are still in the exploratory phase. We are staying on it.”
Many Questions Remain Unanswered
It remains unclear how the medication for constipation affects cognitive depression symptoms in the long term. Does the effect persist? Does the approach work for currently depressed individuals or older people? Could longer use possibly have problematic side effects? All of this needs to be clarified in follow-up studies, which, according to the University of Birmingham, are already in planning.