Many Patients Continue Using Proton Pump Inhibitors After Negative Results From Tests for Reflux Disease

Published:February 23, 2012DOI:

      Background & Aims

      Ambulatory reflux testing is used to evaluate symptoms of gastroesophageal reflux disease (GERD) refractory to protein pump inhibitors (PPIs). We investigated the prevalence of PPI use in patients with negative results from Bravo pH or multichannel intraluminal impedance-pH (MII-pH) tests and factors that might predict the use of PPIs.


      We analyzed data from patients who had undergone Bravo pH monitoring or MII-pH testing at Northwestern University, without evidence of reflux disease. Demographics, endoscopy findings, pathology results, and provider recommendations were obtained via chart review. Eligible patients (n = 90) were contacted by telephone, and a cross-sectional survey was administered with questions about symptom severity, demographics, medication use, and health behaviors. Patients were compared by current PPI use, and statistical analyses were performed by using SAS version 9.2 software.


      Thirty-eight patients (42.2%) reported current PPI use despite a negative result from a pH study. Only 17 patients (18.9%) recalled being instructed to stop taking PPIs; chart review showed documented instructions to stop PPI therapy for 15 patients (16.7%). There were no significant differences in demographic or clinical characteristics among patients compared by current PPI use. Patients taking a PPI were more likely than those not taking a PPI to report troublesome symptoms that affected their daily life, as measured by a questionnaire for the diagnosis of GERD (the GerdQ).


      More than 42% of patients with negative results from pH monitoring studies continue PPI therapy despite physiological data that they do not have GERD.


      Abbreviations used in this paper:

      GERD (gastroesophageal reflux disease), MII-pH (multichannel intraluminal impedance-pH), NSAID (nonsteroidal anti-inflammatory drug), PPI (proton pump inhibitor), SD (standard deviation), VAS (visual analogue scale)
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        • Kahrilas P.J.
        Clinical practice: gastroesophageal reflux disease.
        N Engl J Med. 2008; 359: 1700-1707
        • Everhart J.E.
        • Ruhl C.E.
        Burden of digestive diseases in the United States: part I—overall and upper gastrointestinal diseases.
        Gastroenterology. 2009; 136: 376-386
        • Sandler R.
        • Everhart J.
        • Donowitz M.
        • et al.
        The burden of selected digestive diseases in the United States.
        Gastroenterology. 2002; 122: 1500-1511
        • Shaheen N.
        • Hansen R.
        • Morgan D.
        • et al.
        The burden of gastrointestinal and liver diseases, 2006.
        Am J Gastroenterol. 2006; 101: 2128-2138
        • Liker H.R.
        • Ducrotté P.
        • Malfertheiner P.
        Unmet medical needs among patients with gastroesophageal reflux disease: a foundation for improving management in primary care.
        Dig Dis. 2009; 27: 62-67
        • Flook N.W.
        • Wiklund I.
        Accounting for the effect of GERD symptoms on patients' health-related quality of life: supporting optimal disease management by primary care physicians.
        Int J Clin Pract. 2007; 61: 2071-2078
        • Jones R.
        • Patrikios T.
        The effectiveness of esomeprazole 40 mg in patients with persistent symptoms of gastro-oesophageal reflux disease following treatment with a full dose proton pump inhibitor.
        Int J Clin Pract. 2008; 62: 1844-1850
        • Kahrilas P.J.
        • Shaheen N.J.
        • Vaezi M.F.
        • et al.
        American Gastroenterological Association Institute technical review on the management of gastroesophageal reflux disease.
        Gastroenterology. 2008; 135: 1392-1413
        • Pandolfino J.E.
        • Richter J.E.
        • Ours T.
        • et al.
        Ambulatory esophageal pH monitoring using a wireless system.
        Am J Gastroenterol. 2003; 98: 740-749
        • Srinivasan R.
        • Vela M.
        • Katz P.
        • et al.
        Esophageal function testing using multichannel intraluminal impedance.
        Am J Physiol Gastrointest Liver Physiol. 2001; 280: G457-G462
        • Vela M.
        • Camacho-Lobato L.
        • Srinivasan R.
        • et al.
        Simultaneous intraesophageal impedance and pH measurement of acid and nonacid gastroesophageal reflux: effect of omeprazole.
        Gastroenterology. 2001; 120: 1599-1606
        • Pandolfino J.E.
        • Vela M.F.
        Esophageal-reflux monitoring.
        Gastrointest Endosc. 2009; 69: 917-930
        • Jones R.
        • Junghard O.
        • Dent J.
        • et al.
        Development of the GerdQ, a tool for the diagnosis and management of gastro-oesophageal reflux disease in primary care.
        Aliment Pharmacol Ther. 2009; 30: 1030-1038
        • The EuroQol Group
        EuroQol—a new facility for the measurement of health-related quality of life.
        Health Policy. 1990; 16: 199-208
        • Gershon R.
        • Rothrock N.E.
        • Hanrahan R.T.
        • et al.
        The development of a clinical outcomes survey research application: Assessment Center.
        Qual Life Res. 2010; 19: 677-685
        • Cella D.
        • Yount S.
        • Rothrock N.
        • et al.
        The Patient-Reported Outcomes Measurement Information System (PROMIS): progress of an NIH Roadmap cooperative group during its first two years.
        Med Care. 2007; 45: S3-S11
        • Naunton M.
        • Peterson G.M.
        • Bleasel M.D.
        Overuse of proton pump inhibitors.
        J Clin Pharm Ther. 2000; 25: 333-340
        • Heidelbaugh J.J.
        • Goldberg K.L.
        • Inadomi J.M.
        Overutilization of proton pump inhibitors: a review of cost-effectiveness and risk [corrected].
        Am J Gastroenterol. 2009; 104: S27-S32
        • Hollingworth S.
        • Duncan E.L.
        • Martin J.H.
        Marked increase in proton pump inhibitors use in Australia.
        Pharmacoepidemiol Drug Saf. 2010; 19: 1019-1024
        • Heidelbaugh J.J.
        • Goldberg K.L.
        • Inadomi J.M.
        Magnitude and economic effect of overuse of antisecretory therapy in the ambulatory care setting.
        Am J Manag Care. 2010; 16: e228-e234
        • Heidelbaugh J.J.
        • Inadomi J.M.
        Magnitude and economic impact of inappropriate use of stress ulcer prophylaxis in non-ICU hospitalized patients.
        Am J Gastroenterol. 2006; 101: 2200-2205
        • George C.J.
        • Korc B.
        • Ross J.S.
        Appropriate proton pump inhibitor use among older adults: a retrospective chart review.
        Am J Geriatr Pharmacother. 2008; 6: 249-254
        • Friedenberg F.K.
        • Hanlon A.
        • Vanar V.
        • et al.
        Trends in gastroesophageal reflux disease as measured by the National Ambulatory Medical Care Survey.
        Dig Dis Sci. 2010; 55: 1911-1917
        • van Boxel O.S.
        • Hagenaars M.P.
        • Smout A.J.
        • et al.
        Socio-demographic factors influence chronic proton pump inhibitor use by a large population in the Netherlands.
        Aliment Pharmacol Ther. 2009; 29: 571-579
        • Lacy B.E.
        • Chehade R.
        • Crowell M.D.
        A prospective study to compare a symptom-based reflux disease questionnaire to 48-h wireless pH monitoring for the identification of gastroesophageal reflux (revised 2-26-11).
        Am J Gastroenterol. 2011; 106: 1604-1611
        • El-Serag H.
        • Becher A.
        • Jones R.
        Systematic review: persistent reflux symptoms on proton pump inhibitor therapy in primary care and community studies.
        Aliment Pharmacol Ther. 2010; 32: 720-737
        • Rubenstein J.H.
        • Nojkov B.
        • Korsnes S.
        • et al.
        Oesophageal hypersensitivity is associated with features of psychiatric disorders and the irritable bowel syndrome.
        Aliment Pharmacol Ther. 2007; 26: 443-452
        • van der Velden A.W.
        • de Wit N.J.
        • Quartero A.O.
        • et al.
        Maintenance treatment for GERD: residual symptoms are associated with psychological distress.
        Digestion. 2008; 77: 207-213
        • Wiklund I.
        • Carlsson R.
        • Carlsson J.
        • et al.
        Psychological factors as a predictor of treatment response in patients with heartburn: a pooled analysis of clinical trials.
        Scand J Gastroenterol. 2006; 41: 288-293
        • Wright C.E.
        • Ebrecht M.
        • Mitchell R.
        • et al.
        The effect of psychological stress on symptom severity and perception in patients with gastro-oesophageal reflux.
        J Psychosom Res. 2005; 59: 415-424
        • Johnston B.T.
        • Lewis S.A.
        • Collins J.S.
        • et al.
        Acid perception in gastro-oesophageal reflux disease is dependent on psychosocial factors.
        Scand J Gastroenterol. 1995; 30: 1-5
        • Chey W.D.
        • Mody R.R.
        • Wu E.Q.
        • et al.
        Treatment patterns and symptom control in patients with GERD: US community-based survey.
        Curr Med Res Opin. 2009; 25: 1869-1878
        • Haug T.T.
        • Wilhelmsen I.
        • Svebak S.
        • et al.
        Psychotherapy in functional dyspepsia.
        J Psychosom Res. 1994; 38: 735-744
        • Delgado-Aros S.
        • Cremonini F.
        • Talley N.J.
        Treatment of functional dyspepsia.
        Curr Treat Options Gastroenterol. 2004; 7: 121-131
        • Kiebles J.L.
        • Kwiatek M.A.
        • Pandolfino J.E.
        • et al.
        Do patients with globus sensation respond to hypnotically assisted relaxation therapy?.
        Dis Esophagus. 2010; 23: 545-553
        • Iwakiri K.
        • Kawami N.
        • Sano H.
        • et al.
        Acid and non-acid reflux in Japanese patients with non-erosive reflux disease with persistent reflux symptoms, despite taking a double-dose of proton pump inhibitor: a study using combined pH-impedance monitoring.
        J Gastroenterol. 2009; 44: 708-712
        • Savarino E.
        • Zentilin P.
        • Tutuian R.
        • et al.
        The role of nonacid reflux in NERD: lessons learned from impedance-pH monitoring in 150 patients off therapy.
        Am J Gastroenterol. 2008; 103: 2685-2693
        • Sifrim D.
        • Castell D.
        • Dent J.
        • et al.
        Gastro-oesophageal reflux monitoring: review and consensus report on detection and definitions of acid, non-acid, and gas reflux.
        Gut. 2004; 53: 1024-1031
        • Hirano I.
        • Richter J.E.
        • Practice Parameters Committee of the American College of Gastroenterology
        ACG practice guidelines: esophageal reflux testing.
        Am J Gastroenterol. 2007; 102: 668-685
        • Lee W.C.
        • Yeh Y.C.
        • Lacy B.E.
        • et al.
        Timely confirmation of gastro-esophageal reflux disease via pH monitoring: estimating budget impact on managed care organizations.
        Curr Med Res Opin. 2008; 24: 1317-1327

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