S322 Antidepressants and Microscopic Colitis: A Propensity-Matched Comparison to Bupropion

Introduction: Selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) are some of the most frequently prescribed medications in the U.S., with 150 million prescriptions dispensed in 2022 alone. While SSRIs/SNRIs have long been linked to microscopic colitis (MC), studies on the association remain limited. Given the widespread use of these medications, this study aims to determine whether prior use of SSRIs or SNRIs is associated with an increased odds of developing MC. Methods: A TriNetx case-control study was conducted comparing patients who initiated SSRIs or SNRIs to those prescribed bupropion, an atypical antidepressant not previously implicated in MC. The primary outcome was the development of microscopic colitis after antidepressant initiation. Propensity score matching was performed to balance cohorts on age, gender, race, smoking status, and other relevant confounders. Patients with known alternative causes of colitis and those with recent nonsteroidal anti-inflammatory drug, proton pump inhibitor, or statin use were excluded. Results: After propensity score matching, 10 antidepressant exposure groups (including SSRIs and SNRIs) were compared to bupropion for the development of microscopic colitis. Both SSRIs and SNRIs as medication classes were associated with significantly lower odds of developing microscopic colitis compared to bupropion (SSRI odds ratio [OR [0.68, 95% confidence interval [CI] 0.54–0.86, P = 0.001; SNRI OR 0.64, 95% CI 0.50–0.81, P = 0.0002). Among individual agents, duloxetine (OR 0.79, 95% CI 0.45–0.77, P < 0.0001), escitalopram (OR 0.77, 95% CI 0.60–0.98, P = 0.04), and paroxetine (OR 0.66, 95% CI 0.45–0.97, P = 0.03) were also significantly associated with decreased odds. Other individual agents, including sertraline, fluoxetine, venlafaxine, and desvenlafaxine, were not significantly associated with MC compared to bupropion. Conclusion: In this large, multi-institutional propensity-matched analysis, SSRIs and SNRIs were not associated with increased odds of developing microscopic colitis compared to bupropion. Several agents, duloxetine, escitalopram, and paroxetine, were associated with a significantly lower risk. These findings challenge previous assumptions about the role of serotonergic antidepressants in MC pathogenesis and suggest that their use may not confer additional risk compared to bupropion. Further prospective studies are warranted to better understand underlying mechanisms and confirm these associations in broader populations.