Effects of prucalopride on anxiety and depressive symptoms among constipated patients: A meta‐analysis of randomized controlled trials

Aims Prucalopride, a 5‐HT 4 receptor agonist, has shown potential for rapid anxiolytic and antidepressant effects in preclinical studies. This meta‐analysis aims to evaluate changes in anxiety and depressive symptoms after prucalopride treatment in chronically constipated adults. Methods A systematic search of PubMed, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov , and reports from the Food and Drug Administration and European Medicines Agency was conducted from inception to 1 March 2026. Included studies were double‐blind randomized controlled trials originally designed to assess effectiveness in treating chronic constipation in adults. As preplanned, the primary endpoint was the change in anxiety and depressive symptoms. Standardized mean differences (SMDs) were pooled and analyzed using a random‐effects model. This study is registered with PROSPERO, number CRD42024602454. Results Five randomized controlled trials, including 2,404 participants, were included. The meta‐analysis revealed a significantly greater improvement in anxiety and depressive symptoms derived from quality‐of‐life scores with prucalopride compared with placebo in the random‐effects model (SMD = −0.19, 95% confidence interval [CI] [−0.3117; −0.0707]; P = 0.0019; I 2 = 52%). Improvement in anxiety and depressive symptoms was associated with improvement of constipation, but not with the daily dose of prucalopride. All studies were rated as having some concerns for biais in selection of the reported result. Conclusions Prucalopride improves anxiety and depressive symptoms in chronic constipation. Further studies are needed to explore the potential repurposing of prucalopride for anxiety and depressive disorders.