Introduction: Chronic Pancreatitis (CP) is a fibroinflammatory condition with debilitating symptoms affecting 35-50% of individuals worldwide. Quality of life is severely affected in patient with CP and they are likely to suffer from mental health disorders, including depression. We conducted a systematic review and meta-analysis assessing the prevalence of Depression in patients with CP. Methods: Multiple electronic databases including PubMed, MEDLINE (OVID), PsycINFO, Cochrane Library, Embase, Scopus and Web of Science were searched from inception to June 2022 to identify manuscripts reporting the prevalence of Depression (diagnosed clinically or with a validated scale without language restriction) among patients with Chronic Pancreatitis of any etiology. Case series, reports, editorials, and reviews were excluded. Two independent reviewers extracted data. Disagreements were resolved by a third author. The pooled prevalence was calculated using a random effects model. Heterogeneity was assessed by the inconsistency index (I2). Results: Among 3647 articles identified, 58 studies were identified for full text review, and ultimately nine studies were deemed eligible for inclusion with perfect agreement (kappa=1.0). Five of them were cross-sectional studies, whereas the rest were cohorts. A total of 87136 patients were included in the studies (Table). CP was determined with previous historical diagnosis, the M-ANNHEIM criteria and the presence of a clinical, radiologic and/or endosonographic features. Depression was diagnosed clinically and using Center for Epidemiological Studies 10-item Depression Scale (CESD), Beck Depression Inventory (BDI) and Hospital Anxiety and Depression Scale (HADS). Depression prevalence in patients with CP varied from 11%-70% among the studies. The pooled prevalence of Depression in CP patients was 39% (95% CI 0.26-0.53) (Figure). Four studies included healthy controls with lower prevalences of Depression. Conclusion: Depression among patients with CP deserves a call-to-action due to its medical implications and worsening quality of life. Chronic pain and malabsorption symptoms could predispose to the development of Depression. Our findings raise awareness of the importance of screening patients with chronic pancreatitis for mental health disorders and provide support. Further well-designed clinical trials would be necessary to test tentative therapeutic measures seeking the reduction of symptoms for this specific group of patients.Figure 1.: Forest plot of the prevalence of Depression in patients with Chronic Pancreatitis Table 1. - Baseline characteristics of included studies Study Design Country Duration of follow up or data collection Study Population Chronic Pancreatitis (N) Etiology of Chronic Pancreatitis Diagnosis of Chronic Pancreatitis Depression (N) Depression Diagnosis Cutoff for Depression Controls (N) Type of Controls Depression in Chronic Pancreatitis (%) Depression in Controls (%) Alkhayyat (2021) Retrospective cohort analysis USA 2014 -2019 Patients with diagnosis of CP 67,260 Any etiology Previous diagnosis (chart review) 31477 Clinical NA 30,209,550 Matched healthy controls 47% 14.7% Balliet (2012) Cross-sectional USA NA Patients with nonalcohol-related CP 692 Nonalcohol-related Previous diagnosis (chart review) 360 Center for Epidemiological Studies Depression Scale scores ≥ 10 NA NA 52% NA Chen (2018) Retrospective cohort Taiwan 2000-2010 Patients with newly diagnosed CP 17,733 Any etiology Previous diagnosis (chart review) 1, 898 Clinical NA 35,466 Matched healthy controls 11% 0.9% Szalewska (2016) Cross-sectional Poland NA Patients with CP exacerbation 30 Any etiology Previous diagnosis (chart review) 21 Beck Depression Inventory scores >10 NA NA 70% NA Olesen (2021) Cross-sectional USA and Denmark 2016-2021 Patients with diagnosis of CP 184 Any etiology M-ANNHEIM criteria: (Cambridge III or IV or pancreatic calcifications on cross-sectional imaging) 71 Hospital Anxiety and Depression Scale scores >7 NA NA 39% NA Phillips (2020) Cross-sectional USA and Denmark NA Patients with diagnosis of CP 171 Any etiology M-ANNHEIM criteria: (Cambridge III or IV or pancreatic calcifications on cross-sectional imaging) 66 Hospital Anxiety and Depression Scale scores >7 NA NA 39% NA Shah (2022) Cross-sectional USA 2016- 2021 Patients with CP with and without chronic opioid use 442 Any etiology Presence of a clinical and radiologic (CT or MRCP) and/or endosonographic features 145 Clinical NA NA NA 33% NA Singh (2021) Prospective cohort study India 2013-2014 Patients with Idiopathic CP, with/without diabetes, and >18 years of age 66 Idiopathic CP with/without Diabetes Previous diagnosis based on United European Gastroenterology Guidelines 19 Hospital Anxiety and Depression Scale (HADS) scores >7 152 Matched healthy controls 29% 1% Sarkar (2022) Prospective observational study India NA Patients between 18-60yrs with documented CP who visited the Pancreas Clinic 558 Any etiology 1. Pancreatic calcifications on imaging.2. Pancreatic ductal changes on MRCP or ERCP per Cambridge criteria3. Ductal and parenchymal changes on EUS per Rosemont criteria 261 Beck Depression Inventory II scores >13 67 Matched healthy relatives or caregivers 47% 7.5%