Psychopharmacological Therapy Positively Modulates Disease Activity in Inflammatory Bowel Disease: A Systematic Review

Abstract

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.

Keywords: antidepressants; disease activity; gut–brain axis; inflammatory bowel disease; psychiatric medications.

Figure 1

PRISMA flow diagram describing the paper selection process.

Figure 2

Graphical summary of the studies included in the systematic review. This table summarizes the key studies included in this review, highlighting the effectiveness of certain psychotropic drugs on both gastrointestinal and psychiatric outcomes. The studies are organized by drug class—Antidepressants (Daghdhaghzadeh et al., 2015 [30], Yanartaş et al., 2016 [27], Liang et al., 2022 [31], Chojnacki et al., 2011 [33], Iskandar et al., 2014 [32], Goodhand et al., 2012 [28], Mikocka-Walus et al., 2017 [29], Kane et al., 2003 [34], Kast and Altschuler, 2001 [35], Kast et al., 1998 [36], Hall et al., 2018 [25]), Antiepileptics and Mood Stabilizers (Crockett et al., 2014 [38], D’Onofrio et al., 2024 [39], Zissok, 1972 [42]), and Others (Furlan et al., 2006 [48], Lechin et al., 1985 [47], Lie et al., 2018 [43], Paulides et al., 2022 [49], Smith et al., 2011 [44], Smith et al., 2007 [45], Smith et al., 2013 [46]). The study by Kristensen et al., 2019 [26] was not included because there are no psychiatric/gastroenterological outcomes available for specific psychotropic drugs, but only for classes of drugs (antidepressants). Note: CR (Case-report); CS (Case-series); NASSa (Noradrenaline and specific serotonergic antidepressants); SNRI (Serotonin and norepinephrine reuptake inhibitors); SSRI (Selective serotonin reuptake inhibitors); TCA (Tricyclic antidepressants).

Figure 3

Molecular and immunological mechanisms underlying the anti-inflammatory effects of selected psychiatric medications in inflammatory bowel disease. Selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), venlafaxine, and duloxetine contribute to inflammation modulation through the promotion of M2 macrophage polarization, increased production of anti-inflammatory cytokines (e.g., IL-10, TGF-β), reduction in Paneth cell-mediated epithelial inflammation, and modulation of gut microbiota composition. These drugs also induce a Th1-to-Th2 cytokine shift, reducing pro-inflammatory mediators such as TNF-α, IL-1β, and IFN-γ. Naltrexone inhibits lipopolysaccharide (LPS)-induced TLR4 signaling, reducing ER stress in Paneth cells and the expression of pro-inflammatory interferon genes. Clonidine activates the cholinergic anti-inflammatory pathway (CAIP), resulting in decreased TNF-α levels via autonomic nervous system modulation.