Welcome to my blog ‘Proton Pump Inhibitors: Their Use And Misuse”
What Are PPIs?
Proton pump inhibitors (PPIs) are proven medications of choice for gastroesophageal reflux disease (GERD), acid-related disorders, erosive esophagitis, Barrett esophagus, prevention of gastrointestinal bleeding while on NSAIDs (nonsteroidal anti-inflammatory drugs_, eosinophilic esophagitis, peptic ulcer disease, stress ulcer prophylaxis in critically ill patients, and other indications. (source)
However there is very little evidence to support their use for many other disorders and with long term use there are significant risks that many on these drugs are not aware of. (source)
It is estimated that between 20% and 80% of people worldwide who are using PPIs are doing so without an approved indication. (source)
Their Inappropriate Prescription
There is extensive evidence of the misuse of proton pump inhibitors. Here are just four:
In France, the misuse of PPIs, according to the literature, ranges from 40% to over 80%, depending on the definition used.
In 2011, a study investigated the suitability of the prescription of proton pump inhibitors in patients discharged from several university hospitals in Colorado. The study concluded that 73% of almost one million patients received a proton pump inhibitor without adequate need.
Another study examined the initiation of proton pump inhibitor treatment in hospitalised patients unnecessarily and continued at discharge in western Pennsylvania: 70% of patients who had started a PPI and kept it at discharge did so inappropriately.
Functional dyspepsia is another example of proton pump inhibitor over-prescription. This is because family doctors often recommend these drugs indefinitely, without a reassessment to establish how appropriate it is, or the possibility of reducing the dose or even stopping them. The success of PPIs in these cases is low, ranging from 10% to 30%.
According to a Cochrane systematic review published in 2017 (source), comparing PPI versus placebo, the number of patients that would need to be treated to get a benefit is 11.
There are numerous other examples of this in the literature (source), I won’t bore you with more here.
Adverse Outcomes Of Proton Pump Inhibitor Use
Adverse outcomes due to PPI therapy may be categorised as unrelated or related to gastric acid inhibition.
Allergic reactions, acute interstitial nephritis, chronic kidney disease, poor cardiovascular outcomes, dementia, and drug interactions.
Symptoms include headache and insomnia.
Related To Gastric Inhibition
Gastrointestinal infections, pneumonia, nutrient deficiencies, fractures, spontaneous bacterial peritonitis, and small intestinal bacterial overgrowth. (source)
Symptoms include abdominal discomfort and pain, constipation, diarrhoea, hyponatremia, osteoporosis, interstitial nephritis, B12 impaired absorption or Campylobacter, Salmonella or C. diffcile gastrointestinal infections. (source)
Provider awareness regarding best practice guidelines on PPI use and imparting pertinent education to patients may be the rational approach to safe and effective PPI therapy. (source)
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Coming Off Proton Pump Inhibitors
If someone is on the drug and may not need to be, efforts to come off the PPI may be attempted. Approaches include:
- Stopping the drug.
- Reducing the dose. This can be as practical as going from taking it twice a day to once a day, or, once a day to every other day.
- Using “on-demand” therapy after completing the course of treatment for the specific indication.
Follow-up is recommended for recurrence of manifestations; in the event of recurrence, the PPI may need to be re-instituted. (source)
Evidence nevertheless suggests that excessive and inappropriately prolonged use of Proton Pump Inhibitors is associated with a broad range of adverse effects. Education of provider and patient, stewardship, and motivation are key to appropriate use of PPIs for the right indications. (source)
What’s The Best Way To Come Off PPI?
It has been concluded in the research that the two factors related to the most successful strategies were:
- The clarity and simplicity of the de-escalation protocols, in which patients were instructed on the measures to follow in the event of the reappearance of symptoms,.
- The training of the physicians responsible for deprescribing. (source)
Various Proton Pump Inhibitors de-escalation strategies have been studied, but there is still a lack of consensus regarding the most appropriate approach for cessation of therapy.
In 2017, Canadian Family Physician published de-prescribing guidelines that recommend both abrupt discontinuations, tapering or using “on demand” PPI as viable options. On demand PPI therapy is simply when a patient takes a PPI as needed, when they are experiencing symptoms.
The guidelines further emphasise that PPI de-prescribing should be a shared decision between the provider and the patient. Use of histamine type 2 receptor antagonists (H2RAs) have also been used in de-escalation and are associated with less risk of pneumonia and chronic kidney disease progression/acute kidney injury in comparison PPIs.
One protocol used if symptoms occurred at any step, patients were instructed to return to the dose from the previous step or the initial dose prior to intervention if appropriate. De-escalation could be terminated at any step if the patient experienced acid reflux symptoms. (source)
Patients were monitored every 2 weeks by clinic visit, phone call, or electronic health record messaging and followed for a total of 8 weeks. While other long term side effects require further study when comparing Proton Pump Inhibitors to H2RAs, step down to a less potent acid suppressant such as H2RAs can be considered a significant de-escalation step, while achieving the goal of preventing acid relapse, with the ultimate goal to discontinue all acid-suppressing agents.
How Long Does It Take For Symptoms To Settle?
Typically, acid hyper-secretion takes 3 months to resolve however in one study patients tolerated de-escalation with minimal symptoms after the study period of 8 weeks. Those with successful de-escalation did not experience any disruption in daily activities or inability to eat during the de-escalation process. Given the patient population in the study was complex, commonly with psychiatric co-morbidities and substance use disorders, this is quite impressive. (source)
Both on-demand therapy and stepping down to H2RA therapy increase the risk of symptom relapse more so than lowering the dose does. (source)
It Should Be A Patient Centred Decision
Patient education, including the rationale for PPI de-escalation, as well as what to expect from de-prescribing, should be encouraged.
Eligible patients should be offered the choice of continuing their PPI or trying to reduce/stop their PPI (deprescribing), a choice dependent on values and preferences.
Patients are willing to discuss the option of continuing PPI use or trying to reduce their PPI; however, a range of attitudes exist. The results suggest that reducing a PPI is a preference-sensitive decision. Therefore, patient attitudes should be elicited and incorporated into shared decision making surrounding the decision to continue or try deprescribing a PPI, and structured tools will be helpful to encourage this (source).
Further evidence also suggests shared decision making interventions significantly improve outcomes for disadvantaged patients with low literacy or socioeconomic status (source).
