Adverse Effects of Proton Pump Inhibitors: Fact or Fake News?

Mitchell L. Schubert


Curr Opin Gastroenterol. 2018;34(6):451-457. 

In This Article


PPIs are well tolerated and effective. Despite the ever-increasing number of associations and the widespread media coverage with accompanying brouhaha, the quality of the evidence linking PPIs to a wide range of serious adverse effects is very low. When PPIs are prescribed appropriately, the benefits greatly outweigh potential adverse effects. The absolute risk to an individual is extremely low (less than 1 in 500) and fear of these risks should not dictate prescribing habits. PPIs should be prescribed for patients with GERD, especially those with erosive esophagitis and strictures, as well as for patients at an increased risk for ulcer-related bleeding from NSAIDs, aspirin, and dual antiplatelet therapies. In those patients without a valid indication, PPIs should be discontinued.

Not only has the information derived from these observational studies been unhelpful, but also the unattended consequence is that patients who require PPIs to prevent UGI bleeding are not receiving these medications, mainly due to fear on the part of the patient and provider. Gastroenterologists and primary care providers, who already have limited time to spend with their patients, are incessantly spending additional time discussing and reassuring their patients, both when initiating treatment and on every follow-up visit. Established benefits are being obfuscated by potential unproven risks. We, physicians and researchers, are to blame, both as authors for sensationalizing conclusions and as reviewers for accepting the studies for publication. There used to be a time, not long ago in the galaxy, when science sold itself. Now, investigators must 'sell' their research in order to get published and funded, and journals are more than willing to publish controversial less than optimally executed studies in an effort to improve their impact factor. Although one may argue that these studies, with overstated conclusions that imply but cannot demonstrate cause and effect, ought not to be published, perhaps it can be more strongly argued that, if published, authors must be mandated to strongly indicate that such associations are weak and more likely to be caused by confounding variables both in the study itself and media interviews, conclusions should be tempered and derived the data without added hyperbole, articles should not be published, especially in high impact journals, for the sake of publicity for the journal, and editorials should accompany the papers that place the findings in appropriate context and caution about misinterpretation.

There is no question that PPIs are overprescribed. It has been estimated that 30–50% of prescriptions for PPIs may be inappropriate.[43] When PPIs are prescribed long-term, they should be used at the lowest effective doses and the need for their use should be periodically reassessed.