Comorbid depression and anxiety are associated with a more severe pain phenotype in chronic pancreatitis

Psychiatric comorbidities are common in chronic pancreatitis (CP) and are associated with poorer outcomes. However, the impact of comorbid depression and anxiety and the analgesic role of antidepressants are unclear. We evaluated the associations between depression/anxiety phenotypes with CP-related complications, healthcare utilization, and pain-directed therapies.

We conducted a single-center retrospective cohort study of adults with definite CP from 2015 to 2025. Depression, anxiety, antidepressant prescriptions, CP complications, healthcare utilization, and pain-related therapies were ascertained from electronic health records. Patients were categorized as having no depression/anxiety, depression alone, anxiety alone, or comorbid depression/anxiety. Multivariable logistic and negative binomial regression models assessed associations with study outcomes, adjusting for demographics, follow-up duration, comorbidity burden, alcohol use disorder, and tobacco use. Secondary exploratory models additionally adjusted for antidepressant prescriptions.

Among 1979 patients with CP, 33.8% had comorbid depression/anxiety, 10.9% depression alone, and 11.2% anxiety alone. Comorbid depression/anxiety and anxiety alone were independently associated with greater chronic pain (p < 0.001), hospitalizations (p < 0.01), emergency visits (p < 0.01), abdominal CT scans (p < 0.01), and opioid prescriptions (p < 0.01). Depression alone was independently associated with greater risk of chronic pain (p < 0.001), but not with other outcomes. None of the psychiatric comorbidity groups was associated with endoscopic or surgical treatments. Adjustment for antidepressants attenuated study associations, particularly on healthcare utilization and opioid prescriptions.

Depression and anxiety in CP, especially when comorbid, are associated with increased pain-related morbidity and healthcare utilization. Our findings highlight the importance of routine screening for psychiatric comorbidities in patients with painful CP.