Objective/Hypothesis: To study the treatment response of Globus pharyngeus to ppi/prokinetic combination, and the role of antidepressants in non-responders. The purpose of this study is to devise a guideline for managing Globus pharyngeus which otherwise is a poorly understood and managed condition. Study design: It is a prospective non-randomised study where OPD visiting patients have been followed over a course of 6 to 12 months. Methods: 54 patients of Globus pharyngeus diagnosed, with any organic condition ruled out, were put on esomeprazole-domperidone/levosulpride combination. Patients were followed over 3 weeks and 6 weeks period. The non-reponders were put on antidepressant fluoxetine in addition. The response was again gauged at 6 weeks and 12 weeks. Results: 11 patients responded fairly well to the initial treatment of esomeprazole-domperidone/levosulpride. Rest of the 43 patients were put on Fluoxetine in addition and followed over 6 weeks and 12 weeks time. Out of them, 29 patients responded to a varied extent and the remaining either did not respond or were lost to follow-up. Conclusion: Only a minority of the Globus pharyngeus patients seem to respond to acid suppressant/prokinetic agents. Involvement of a psychiatrist early in the care of these patients is recommended as quite a number of non-responders to the routine treatment do well if managed with anitidepressants as well pointing to the underlying mood ailments.