BACKGROUND & AIMS: Data on the benefit of selective serotonin reuptake inhibitors (SSRIs) in irritable bowel syndrome (IBS) are conflicting. The longitudinal relationship between clinical symptoms and sensitivity to barostat-mediated rectal distension in IBS remains unclear. We assessed the benefit of citalopram and explored the relationships between symptoms, quality of life (QOL), and rectal sensitivity to barostat distension in non-depressed IBS patients. METHODS: Patients from primary, secondary, and tertiary care settings were randomly assigned to receive citalopram (20 mg/day for 4 weeks, then 40 mg/day for 4 weeks) or placebo in a study with double-masking and concealed allocation. Symptoms were assessed weekly, and IBS-QOL and rectal sensation by barostat were assessed at the beginning and end of the study. RESULTS: Patients receiving citalopram did not achieve a higher rate of adequate relief of IBS symptoms than patients receiving placebo (12/27 [44%] vs 15/27 [56%]; P = .59), regardless of IBS subtype. The odds ratio for weekly response with citalopram vs placebo was 0.80 (95% confidence interval, 0.61-1.04). Improvements in specific symptom and IBS-QOL scores were not superior for citalopram. Changes in IBS-QOL score and pressure eliciting pain showed a modest correlation (r = 0.33; 95% confidence interval, 0.03-0.57), but changes in symptoms and IBS-QOL scores or rectal sensitivity were not correlated substantially. CONCLUSIONS: Citalopram was not superior to placebo in treating non-depressed IBS patients. Changes in symptoms were not substantially correlated with changes in rectal sensation assessed by barostat. Any benefit of citalopram in non-depressed IBS patients is likely to be modest at best.