Review Article

Rethinking the "Ladder" Approach to Reflux-like Symptom Management in the Era of PPI "Resistance" - A Multidisciplinary Perspective

A. Pali S. Hungin; Carmelo Scarpignato; Laurie Keefer; Maura Corsetti; Foteini Anastasiou; Jean W. M. Muris; Juan M. Mendive; Peter J. Kahrilas


Aliment Pharmacol Ther. 2022;55(12):1492-1500. 

In This Article

Abstract and Introduction


Background: Despite widespread adoption of potent acid suppression treatment with proton pump inhibitors (PPI) for reflux-like symptoms, persistent symptoms are commonly reported in primary care and community studies.

Aims: This multidisciplinary review critically evaluates how the management of reflux-like symptoms could better reflect their multifactorial pathophysiology.

Methods: A panel of experts (from general practice, gastroenterology and gastropsychology) attended a series of workshops to review current management and propose a framework for the provision of more individualised care.

Results: It was agreed that the perceptual (as well as the physiological) causes of reflux-like symptoms should be considered at the start of management, not as a last resort when all else has failed. A short course of PPI is a pragmatic approach to address reflux-like symptoms, but equally important is counselling about the gut-brain axis and provision of symptom-specific behavioural interventions for those who show signs of somatisation, hypervigilance or co-existing disorders of gut-brain interaction. Other low-harm interventions such as lifestyle and dietary advice, should also be better integrated into care at an early stage. Multidisciplinary care management programmes (including dietary, weight loss, exercise and behavioural intervention) should be developed to promote greater self-management and take advantage of the general shift toward the use of remotely accessed health care resources.

Conclusions: Management of reflux-like symptoms should be adapted to reflect the advances in knowledge about the multifactorial aetiology of these symptoms, addressing both acid-related and behavioural components early in management. The time has come to treat the patient, not the "disease".


Oesophageal symptoms are extremely common but the response to treatments targeting gastro-oesophageal reflux disease (GERD) can be highly variable.[1,2] This challenge has, in part, been fostered by the Montreal definition of GORD which provided a rationale for diagnosis and treatment based on the presence of reflux-like symptoms (heartburn, regurgitation, chest pain) or oesophageal injury, assumed to be the result of refluxing gastric contents.[3] However, equating non-specific oesophageal symptoms (often with minimal contribution of underlying acidic gastro-oesophageal reflux[4]) with reflux oesophagitis is a gross oversimplification. Although proton pump inhibitors (PPIs) have an excellent safety profile and have revolutionised the treatment of oesophagitis,[5] the physiological determinants of reflux-like symptoms and reflux oesophagitis only partly overlap, and PPI efficacy is less impressive for symptomatic syndromes (40%–60%).[2] This is exemplified by the significant proportion of patients with refractory symptoms that emerged after the widespread adoption of PPI therapy as first-line treatment. In fact, up to half of the PPI-treated patients with reflux-like symptoms in primary care and community-based studies report persistent symptoms.[6,7]

While subsequent consensus has acknowledged that non-reflux factors (e.g., altered perception, visceral hypersensitivity) contribute to refractory symptoms,[8] no clear clinical strategy has emerged to adequately address this in primary care, and escalation or modification of PPI therapy remains the primary strategy to address refractory symptoms.[2,9] This raises two major concerns about the modern-day acid-targeted approach to management; unnecessarily high levels of chronic exposure to potent acid inhibitors[10] and poor outcomes in patients with persistently unresolved symptoms.[6,7] Clearly, a clinical pathway that better addresses the aetiology of symptoms is needed to achieve the desired symptomatic improvement for patients.