to one PPI switching to another one is usually recommended 192]. Administartion of PPIs is not as robust at resolving GERD symptoms in patients with negative endoscopy. Only 61% of patients experienced resolution of heartburn with PPIs, which is still superior compared to 40% with H2RAs administration 193, 94]. Thus, response of patients with NERD to a standard dose of PPI is approximately 20%-30% lower than that of patients with erosive esophagitis. Inadequate symptom response to once-daily PPI therapy affects up to 40% of GERD patients and is the most common issue faced by gastroenterologists [59]. The majority of these patients originate from the group with NERD and functional heartburn. In the setting of PPI failure, experts recommend an escalation to twice-daily dosing of PPIs to improve