To our knowledge, our study is the first of its kind to show continued PPI use despite physiologic evidence contraindicating the presence of acid reflux. Our findings suggest that a large proportion of patients with negative results from pH monitoring studies continue PPI therapy despite evidence contradicting the presence of GERD. In addition, most patients did not recall being counseled to stop their PPI, and such counsel was not documented in the majority of patients’ medical records. While PPIs are often prescribed for gastroprotection with concurrent ASA and NSAID use, this did not appear to be a major contributing factor for PPI use in our patient sample.
Our results may not be surprising, considering that PPI overuse has been documented in numerous studies, both for inpatient and outpatient settings.17–21
Possible factors contributing to this overuse have been postulated, including practice setting, physician type, formulary status, and direct-to-consumer advertising.18,22–24
It is likely that similar factors contributed to our results. Interestingly, there were no potential demographic or clinical predictors of continued PPI use, other than the use of alcohol. This suggests that those patients still taking a PPI may be avoiding substances or health behaviors that could exacerbate symptoms. This possibility is also suggested by our finding that the vast majority of patients (regardless of PPI use) have used specific health behaviors to address their symptoms.
Despite negative results from pH testing, a significant proportion of patients had GerdQ scores that would be considered diagnostic of GERD based on the questionnaire scoring parameters.13
These patients were also more likely to be taking a PPI. The GerdQ was primarily developed as a diagnostic questionnaire and initially revealed comparable sensitivity and specificity at diagnosing GERD as that of a clinician.13
More recently, Lacy et al. compared the GerdQ with 48-hr ambulatory pH monitoring and found more limited sensitivity and specificity than originally published for diagnostic purposes.25
Our study was not designed to compare or determine characteristics of the GerdQ, but, similar to Lacy’s findings, it does reveal that a significant proportion of patients have high scores (considered diagnostic of GERD) in the absence of physiologic data.
The GerdQ data also revealed that patients currently taking a PPI continue to have symptoms that affect their daily life. There are likely multiple reasons for this. In a recent systematic review by El-Serag et al. of patients with GERD who were taking a PPI, persistent GERD symptoms ranged from 17–32% (depending on symptom) across 19 studies included in the review.26
They found that persistent GERD symptoms on PPI therapy were associated with studies performed in the US and those studies with a higher proportion (>60%) of female participants. They also found that persistent symptoms were associated with decreased psychological and physical “well-being.” Indeed, multiple studies have shown associations between stress and anxiety and persistent GERD symptoms despite PPI therapy.27–30
Our patient sample was predominantly female () and many patients in our study, regardless of PPI use, reported a history of anxiety and/or depression and medication use for these disorders. Thus, our results may be partially attributable to somatization, which has been shown to be associated with esophageal hypersensitivity and increased perceived symptoms.27, 30, 31
Many patients in our study could be classified as having “functional heartburn” simply based on the negative pH testing results with continued symptoms.
In a recent US community-based survey of 1,347 GERD patients, Chey et al. found that the majority of patients were satisfied with their treatment; however, 42% of them were using supplemental medication and ~27% were dissatisfied with their PPI therapy.32
They also found that 40% of patients were not taking their medication correctly (i.e., before meals), highlighting opportunities for cost-effective intervention strategies and patient counseling measures.32
Our study revealed potential opportunities for clinicians to improve patient counseling and perhaps take a more systematic approach to their patients whose reflux testing yields negative results.
Our findings suggest that clinicians should routinely recommend a trial of stopping PPI therapy for those patients who lack evidence of disease. Patients also reported very little use of alternative or complementary therapies for their symptoms, for which there is some evidence of benefit in treating functional GI disorders.33–35
This may indicate another potential area for clinicians to explore with their patients who seek relief from GERD symptoms.
Although this is the first study to determine PPI use after reflux testing with negative results, there are multiple limitations. The generalizability of our results may be limited because the study was conducted at a single academic tertiary medical center staffed by clinicians with expertise in treating esophageal disorders. In addition, the patient sample was predominantly white and of a higher socioeconomic status compared with the general population. This was a retrospective study, and the findings from the phone survey may have been subject to recall bias. However, the primary outcome of current PPI use should not have been affected by this. Our chart review data were limited as the referral system at our institution is open access for pH testing and is utilized by an assortment of physicians. We have access to testing results but do not manage therapy for all the patients. Physician recommendations to stop PPI therapy may have been discussed but not documented. Also, of the patients identified in our records as eligible for the study, 63 (31.5%) were not successfully contacted after multiple attempts.
Another potential limitation is the possible role of non-acid reflux disease in contributing to GERD symptoms that has been highlighted in recent years.36–38
In this study, it is possible that some of the patients who had Bravo™ pH testing could have non-acid reflux contributing to their symptoms. However, even if the prevalence of non-acid reflux was similar as has been identified in previous studies (~18%)37
, there would still be a substantial proportion of patients on PPI therapy without reflux disease (acid or non-acid).
Overall, these results highlight the need for improved strategies to identify alternative diagnoses and treatment strategies for patients whose symptoms are inadequately relieved by PPIs. Professional society guidelines advocate diagnostic testing (endoscopy and reflux testing) for patients whose symptoms are not fully responsive to a limited trial of PPI therapy.1,12,39
A recent cost effectiveness analysis showed that early and increased use of pH monitoring could lead to less PPI use without a significant increase in cost to managed health care plans.40
However, testing alone is not sufficient if practitioners fail to communicate results to patients adequately or act upon them.
In summary, a large proportion of patients with negative results from pH monitoring studies continue PPI therapy despite physiologic evidence contradicting the presence of GERD. Although this study was not designed to compare testing modalities, prospective studies are needed to determine how different testing modalities affect subsequent medication use, prescription patterns, and patient outcomes. Future research should include efforts to better stratify patients who respond poorly to PPIs based on physiologic parameters, evaluate strategies that expedite diagnostic testing and improve follow up, and collect prospective outcome data to guide therapy.