Can a Common Laxative Help Restore Memory After Depression?

What if a medication used for years to treat constipation could also improve memory, attention, and concentration in people who have experienced depression? A new study presents surprising results and points to a completely unexpected way to combat so-called "brain fog."

Depression is known to cause sadness, loss of interest, and sleep disturbances, but many people live with another equally debilitating symptom: "brain fog." It hinders concentration, reasoning, learning, and memory, and can persist even after emotional symptoms have improved.

For many patients, this difficulty in thinking clearly is one of the biggest obstacles to returning to work, studies, and normal routines. Unfortunately, traditional antidepressants do not always alleviate these cognitive issues, prompting scientists to seek new treatment alternatives.

One of the most intriguing approaches involves prucalopride, a drug widely used to treat chronic constipation. While it may seem odd to imagine a laxative being studied for brain health, the explanation lies in serotonin.

In addition to acting on the gut, prucalopride stimulates a specific type of serotonin receptor that is also found in the brain. Previous studies on animals and healthy volunteers suggested that this receptor plays a role in processes vital to memory, learning, attention, and brain plasticity, the brain's ability to form new connections and adapt throughout life.

To test this hypothesis, the researchers recruited fifty adults who had already faced at least two episodes of depression throughout their lives, but who had been recovered for at least six months and were not using psychiatric medications. The idea was to specifically study cognition, without intense symptoms of depression interfering with the results.

Participants were randomly divided into two groups. One received prucalopride daily for about a week, while the other received a placebo, a capsule without the active ingredient. Neither the volunteers nor the researchers knew who was receiving which treatment until the end of the study, a method used to prevent expectations from influencing the results.

Before and after treatment, everyone underwent an extensive battery of computerized tests that assessed different brain functions. Scientists looked at memory for words, working memory, which we use to hold information temporarily while solving problems, speed of reasoning, attention, the ability to recognize facial expressions, and the processing of emotional information.

Instead of relying solely on participants' perceptions, researchers used objective tasks that measure, with high precision, response times and the number of correct answers in each activity.

The results were encouraging. Participants who received prucalopride recalled more words following memory tests, responded more quickly during complex tasks requiring them to hold information in mind while solving problems, and identified facial expressions with greater accuracy.

Overall, the treated group performed better on various cognitive tasks unrelated to emotions. Interestingly, the drug had virtually no effect on emotional processing, suggesting that its primary impact is on functions such as memory, attention, and processing speed, rather than directly on mood.

The authors emphasize that these results do not mean prucalopride should immediately be used as a treatment for depression. The study was relatively small, lasted only a few days, and evaluated individuals who were already in remission. Larger, long-term studies will still be needed to confirm the efficacy and safety of this approach.

Even so, the research opens up a fascinating new perspective: perhaps medications already available for other conditions could, in the future, help restore cognitive functions that remain impaired after depression, offering new hope to millions of people living with a persistent sense of "mental slowness" even after emotional recovery.

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Pro-cognitive effects of 5-HT4 receptor agonism in individuals with remitted depression

Angharad N. de Cates, Sorcha Hamilton, Anutra Guru, Merethe Blandhol, Michael Colwell, Philip J. Cowen, Meghan Simmons, Bailey Jones, Catherine J. Harmer, and Susannah E. Murphy 

Psychological Medicine. 15 June 2026; 56:e178.

DOI: 10.1017/S0033291726104450

Abstract: 

Cognitive impairment is a common and persistent feature of depression, yet it remains poorly understood and inadequately treated. Preclinical and human studies suggest that stimulating 5-HT4 receptors (5-HT4R) enhances neuroplasticity and improves cognition. This novel study examines the cognitive effects of 5-HT4R agonism in adults with a history of recurrent depression. Fifty participants who were not currently depressed but had experienced at least two previous episodes of depression were randomized in a double-blind design either to prucalopride (2 mg daily, titrated from 1 mg) or to placebo for 7–10 days. Participants completed self-report questionnaires and a task battery at baseline and post-intervention assessing declarative memory, working memory, emotional processing, and executive function. Compared to placebo, prucalopride significantly improved word recall on an auditory verbal learning task and was associated with faster response times on a complex working memory task without loss of accuracy. It also improved the accurate recognition of rapidly presented facial expressions. Composite analysis of non-emotional tasks identified that the prucalopride group participants post-intervention were faster and more accurate than at baseline compared to those receiving placebo. Prucalopride had minimal effects on affective cognition, consistent with previous findings. Cognitive improvements were independent of baseline mood symptoms or self-reported cognitive difficulties. Short-term 5-HT4R agonism improved performance on multiple objective cognitive measures in individuals with remitted depression. These findings replicate our previous results in healthy volunteers showing a pro-cognitive effect of prucalopride and support a role for 5-HT4Rs as a promising target for cognitive enhancement in mood disorders.