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

Article Excerpt
Byline: Michael Shapiro, MD, Anmarie Moore, MD, and Ronnie Fass, MD

Abstract: 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)

Key Words: Gastroesophageal reflux, Proton pump inhibitor therapy

Although proton pump inhibitors (PPIs) are highly effective in the treatment of gastroesophageal reflux disease (GERD), clinical failure is seen regularly, not only in GI clinics but also in primary care offices. In fact, the prevalence of failure with PPIs has increased in proportion to the expanding indications of their use. Between 25% and 40% of patients with GERD remain symptomatic while taking standard (once-daily) doses of a PPI1,2; most of these patients continue to experience GERD symptoms even with higher doses.

Patients are considered to have refractory GERD if PPI therapy is unsuccessful. We define PPI failure as the inability to achieve complete esophageal healing and/or satisfactory symptomatic response after a full course (2 months) of once-daily PPI therapy. This definition allows for the inclusion of patients who perceive their persistent symptoms as bothersome, regardless of frequency or severity.

In this article, we address the possible causes of PPI failure and review possible diagnostic and therapeutic approaches.

EFFECTIVENESS OF PPI THERAPY

The 3 usual presentations of GERD are nonerosive reflux disease, erosive esophagitis, and Barrett esophagus. In the primary care setting, as many as 70% of patients with typical symptoms of GERD have nonerosive reflux disease, which is the most common presentation of GERD.3 The proportion of patients with nonerosive disease who respond to a standard dosage of a PPI is approximately 20% to 30% lower than that of patients with erosive esophagitis.

Nonerosive reflux disease

In a systematic review of the literature, the symptomatic response rate to PPI therapy was 36.7% (95% confidence interval [CI], 34.1% - 39.3%) in patients with nonerosive reflux disease and 55.5% (95% CI, 51.5% - 59.5%) in those with erosive esophagitis.4 The therapeutic gain was 27.5% in those with nonerosive disease and 48.9% in those with erosive esophagitis. In patients with nonerosive disease, the time to sustained symptom response was 2 to 3 times longer than it was in patients with erosive esophagitis.

Approximately 30% to 50% of patients with nonerosive disease demonstrate esophageal acid exposure within the physiological (normal) range. Patients...

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