BACKGROUND: Traditional treatment of functional dyspepsia (FD) is unsatisfactory in a subgroup of patients with FD, and the potential role of antidepressant medications also has not been definitely clarified. To provide more evidence for future optimal practice recommendations, we reviewed a 1-year clinical database of antidepressant agents applied in outpatients with FD. METHODS: Clinical presentations, treatment course, and outcomes were determined by chart review of patients referring to the functional gastrointestinal disorders specialist clinic. One hundred thirty patients with FD were included for further analysis. RESULTS: Patients were treated with different antidepressant drugs according to individual symptoms. The most commonly used drugs were flupenthixol melitracen and fluoxetine. Improvement and complete remission occurred in 93.8% and 54.6% of patients, respectively. There was a trend toward superior outcome for citalopram compared to sulpiride and mirtazapine in overall analysis. Meanwhile, regimens containing fluoxetine had significant increased remission rate compared to any other antidepressant regimens in postprandial distress syndrome subgroup analysis. Furthermore, older patients were more likely to achieve remission. However, sex and symptom duration were not associated with symptom remission. Finally, 11.5% of patients experienced adverse events. CONCLUSIONS: This retrospective cohort study indicated that small dose antidepressant therapy, especially citalopram and fluoxetine, is an effective and well tolerated treatment option for refractory FD.