Depression, anxiety, and perceived stress are common comorbidities in patients with inflammatory bowel disease (IBD) and may negatively influence the disease course. Likewise, severe IBD may contribute to the development or worsening of psychiatric symptoms. Despite the established relevance of the gut–brain axis and frequent use of psychotropic medications in IBD patients, limited evidence exists regarding the effects of psychiatric treatments on gastrointestinal disease activity. Therefore, the aim of this systematic review is to evaluate the effectiveness of psychiatric therapies on gastrointestinal symptoms and disease activity in patients with IBD. The work was conducted in accordance with PRISMA guidelines. Searches were performed across PubMed, Web of Science, and Scopus up to July 2024. Eligible studies evaluated the effectiveness of psychiatric medications—including antidepressants, antipsychotics, anxiolytics, sedative-hypnotics, mood stabilizers, anticonvulsants, and others—on at least one gastrointestinal outcome in patients with IBD. Outcomes included changes in commonly used clinical and endoscopic scores for Crohn’s disease (CD) and ulcerative colitis (UC), number of bowel movements, stool consistency, presence of blood in stool, severity of abdominal pain, as well as in surrogate markers of disease activity following treatment. Out of 8513 initially identified articles, 22 studies involving 45,572 IBD patients met the inclusion criteria. Antidepressants, particularly bupropion, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), venlafaxine, and duloxetine, were associated with improvements in IBD activity scores, including Crohn’s Disease Activity Index (CDAI) and Simple Endoscopic Score for Crohn’s Disease (SES-CD) for CD, Mayo score and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) for UC. Case reports highlighted potential benefits of pregabalin and lithium carbonate, respectively, showed by the reduction in clinical and endoscopic score of disease activity for pregabalin and improvement of UC symptoms for lithium carbonate, while topiramate showed limited efficacy. Clonidine and naltrexone determined the reductions in clinical and endoscopic score of disease activity, including CDAI and Crohn’s disease endoscopy index severity score (CDEIS) for CD and Disease Activity Index (DAI) for UC. Despite the limited data and study heterogeneity, antidepressants, naltrexone, and clonidine were associated with improvements in IBD activity. Larger, prospective studies are needed to confirm the therapeutic potential of psychiatric medications in modulating IBD activity and to guide integrated clinical management.

Psychological distress and gut dysbiosis play key roles in IBD. This study investigated whether specific psychopathological and gut microbiota features predict adverse outcomes in UC patients. This retrospective cohort study included 35 UC patients recruited in 2019. Baseline assessments involved clinical interviews, psychiatric evaluations, and stool sampling. In 2024, follow-up interviews and medical record reviews assessed disease progression, including biologic therapy failure, hospitalization, surgery, and diagnosis changes. Disease activity was measured via the Mayo score. Psychological testing included MMPI-2, STAI-Y2, GSES, CD-RISC, and TAS-20. Patients with biological therapy failure showed increased levels of Proteobacteria, Fusobacteria, Enterobacteriaceae, and Trabulsiella, while Firmicutes were less abundant. UC-related hospitalized patients had lower levels of Rikenellaceae, Ruminococcaceae, Faecalibacterium, Lachnospira, Methanobrevibacter, and Phascolarctobacterium compared to non-hospitalized patients. Hospitalized patients scored higher on the Sc clinical scale and the OBS and HEA content scales. Acidaminococcus and Bilophila were more abundant in patients who underwent surgery. PCA revealed differences between patients with and without biological failure. Logistic regression found that Fusobacteria were negatively correlated with the failure of three or more biologics, while Hy and Pd were positively correlated. Pa and Pt were negatively correlated with multifailure. Obsessiveness, health concerns, somatization, and reduced SCFA-producing bacteria may predict UC-related adverse outcomes.