What to do when doubling the dosage isn't enough -- Refractory gastroesophageal reflux disease-what next?

• Published in: The Journal of respiratory diseases Vol. 28; no. 10; p. 427
• Main Author: Shapiro, Michael
• Format: Journal Article
• Language: English
• Published: Darien CMP Medica, LLC 01.10.2007; MultiMedia Healthcare Inc
• Subjects: Care and treatment; Diagnosis; Dosage and administration; Drug therapy; Gastroesophageal reflux; Management; Proton pump inhibitors; United States
• ISSN: 0194-259X

As many as 70% of patients with gastroesophageal reflux disease have nonerosive disease, including functional heartburn. These patients are less likely than those with erosive esophagitis to respond to a standard course of proton pump inhibitor (PPI) therapy. Nonadherence to therapy is the most likely cause of persistent symptoms. Other causes of treatment failure include weakly acidic reflux, visceral hypersensitivity, duodenogastroesophageal reflux, and delayed gastric emptying. Diagnostic modalities such as upper endoscopy and multichannel intraluminal impedance may provide clues to the underlying cause. The usual approach to patients who have refractory symptoms while receiving once-daily PPI therapy is to double the PPI dose. In patients with symptoms of regurgitation or a sour or bitter taste in the mouth, the addition of a transient lower esophageal sphincter relaxation reducer may be useful. Pain modulators, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may also be considered. (J Respir Dis. 2007;28(10):427-435) Ambulatory 24-hour esophageal pH monitoring has been widely used in evaluating patients with GERD for abnormal distal esophageal acid exposure. However, this technique appears to have limited value in patients who experience failure of once-daily PPI therapy and to be noncontributory in those in whom twice-daily therapy fails.23,24 Multichannel intraluminal impedance has been increasingly used in patients with GERD in whom twice-daily PPI therapy has failed. This test may demonstrate weakly acidic reflux as a cause for symptoms in a subset of patients. The most common strategy, which has become the standard of care in clinical practice, is to double the PPI dosage.25 Studies suggest that most patients who experience failure with once-daily PPI therapy continue to be symptomatic with twice-daily therapy.26 A double dose of a PPI appears to benefit patients with functional heartburn.27 However, the maximum dosage that will relieve symptoms or increase the number of responders is not yet known. Furthermore, because most patients who continue to be symptomatic with twice-daily therapy have normal esophageal acid exposure,28 it is highly unlikely that increasing the PPI dosage to 3 or more times daily will provide significant additional benefit.