to low-intensity reflux events is suggested as the underlying mechanism for symptom generation [96, 97]. Thus, it is clear that treatment success depends on identification of the putative mechanism of the PPI failure. In case of residual acid reflux, increasing the PPI dose to twice daily, switching to another PPI or adding H2RA mainly for noncturnal reflux could offer a successful therapy option (98]. 5.1.1. New Agents. New agents have recently emerged for the treatment of patients nonrespondent to PPI treatment. To address this clinical issue, research efforts have focused on "reflux inhibition"-that is, inhibition of transient lower esophageal relaxations (TLESRs), the predominant mech- anism of the y-aminobutyric (GABA) type B (GABAB) receptor has emerged as one of the most