Appropriate prescribing and deprescribing of proton pump inhibitors

Clinical question

How can I prescribe proton pump inhibitors (PPIs) most effectively in my patients? What is the likely diagnosis that requires PPIs, and how should patients be treated?

Bottom line

PPIs are among the most prescribed drugs in Canada, yet 30% to 40% of PPI prescriptions lack an ongoing indication.^1,2 Family physicians are well placed to reduce prescribing of PPIs since they write 75% of PPI prescriptions,³ but other members of the care team, including pharmacists, patients, and gastroenterologists, also play important roles. Reducing PPI overuse involves the following: prescribing PPIs only for evidence-based indications and with the appropriate dose and duration; regular consideration of deprescribing (stopping or dose reduction); and knowing and documenting reasons for patients to continue taking PPIs long term.

Case

A 59-year-old woman is complaining of a burning sensation behind her sternum. She has been experiencing this most days of the week and it is interfering with her sleep. Antacids have been helping “a bit.” She does not take any other medications.

Evidence

Rates of PPI use vary depending on the population and setting. In Alberta, 11% of the general population receive at least 1 PPI prescription each year while around 30% of Canadians 65 years and older take PPIs.^3,4 It is estimated that 30% to 40% of patients taking PPIs over the long term potentially lack an indication for long-term use.^1,2 While PPIs provide symptom relief in gastroesophageal reflux disease (GERD) and dyspepsia, the response rate for GERD is higher, with up to 80% of patients having symptom resolution in 8 weeks.^5-7 The initial recommended treatment duration for PPIs is typically up to 8 weeks.^5,7 Some patients will have an indication to continue a PPI long term (eg, Barrett esophagus, patients with high gastrointestinal [GI] bleed risk who require a nonsteroidal anti-inflammatory drug [NSAID]). In patients who have been treated long term (eg, >1 year) whose symptoms have resolved and have no indication for ongoing use, it is reasonable to consider a trial of deprescribing the PPI.⁸ Sometimes PPIs may have been started for indications where there is lack of evidence for benefit (eg, chronic cough).⁹ Consideration of deprescribing is also warranted in these cases.

Options for deprescribing long-term PPIs include tapering or taking them on demand (as needed until symptoms resolve) or lowering to a dose and frequency that prevents symptoms from recurring.^8,10,11 Abruptly stopping PPIs in those who have taken them long term has a higher risk of temporary rebound acid hypersecretion and symptom relapse and is generally not recommended.^10,11

Adverse effects of long-term PPI use have been extensively researched but most studies have weak designs.¹² Most purported long-term adverse effects are unlikely to be causally related to PPIs.¹³ Rare established adverse effects include a small increased risk of enteric infections, low magnesium levels, and diarrhea.¹³ Despite their safety, unnecessary long-term PPI use contributes to pill burden, drug costs, and potential drug interactions, and thus remains an important target for deprescribing in appropriate patients.

Approach

In all patients it is important to determine whether lifestyle issues, such as smoking, obesity, and unhealthy diet, have contributed to symptoms. When a prescription for a PPI is initiated, patients should have an appropriate indication for its use, be started on the right dose, and receive instructions on the correct duration of treatment. Table 1 provides further details on these 3 points.^14-18 The table highlights principles of appropriate PPI prescribing for the most common primary care indications (eg, symptomatic GERD, dyspepsia, preventing GI bleeding), and indications based on gastroenterology specialist assessment.

In primary care, a diagnosis of GERD can be made when patients present with dominant symptoms of heartburn or regurgitation.^5,19 In dyspepsia, epigastric pain or discomfort is the dominant symptom but heartburn can be present as an associated symptom.¹⁹ Overlap between these 2 entities is common. In Canada, GERD is more common than dyspepsia.²⁰ For most indications the starting dose of PPI is once daily in the morning before breakfast. The main indications for a twice-daily starting dose are treatment of GI bleeding and anti–Helicobacter pylori therapy (for the duration of antibiotic therapy). A useful clinical pearl is that PPIs are effective in ulcer-like dyspepsia (where the main symptom is epigastric pain) and reflux-like dyspepsia (heartburn also present) but not in dysmotility-like dyspepsia (where upper abdominal bloating is the dominant symptom).²¹

The recommended duration of initial therapy is 4 to 8 weeks. After this time, patients should be reassessed to see if symptoms have improved. Sometimes it may be necessary to continue therapy for a longer period (another 4 to 8 weeks) or give a trial of twice-daily PPIs if the symptom response was equivocal, and then follow up to assess symptoms. Table 1 gives guidance as to whether patients should be tested for H pylori.^14-18 Testing and treating for H pylori provides long-term benefit in some but not all patients who experience dyspepsia.²² In contrast, the clinical course of GERD (ongoing symptoms, need for PPI) is not altered by H pylori treatment.²³ The decision to start patients on long-term (maintenance) PPI therapy for GERD or dyspepsia is based on recurrence of symptoms once the PPI is stopped. Some patients will need long-term therapy or, over time, need twice-daily PPIs to maintain control of their symptoms.²⁴ Table 1 lists the indications for long-term maintenance therapy, including patients with indications based on endoscopy findings such as Barrett esophagus.^14-18

Overall, it is best practice to review a patient’s medication list at regular intervals, which includes assessing whether discontinuation or dose reduction of a medication is possible (deprescribing). Reasons for deprescribing PPIs include lack of ongoing indication (eg, patient is no longer taking NSAIDs), the medication is no longer required (eg, GERD symptoms have resolved), the dose can be lowered, or no clinical benefit is evident (dysmotility-like dyspepsia, chronic cough).

Figure 1 shows several evidence-based strategies to approach PPI tapering.¹⁶ Some patients will report a brief period of symptom recurrence when a long-term PPI is stopped. This is thought to be due to rebound acid hypersecretion and is temporary, typically lasting for 1 to 2 weeks.²⁵ Patients should be warned about this, as it is not an immediate reason to restart the PPI. Short-term use of over-the-counter antacids is often sufficient to control these symptoms. The Choosing Wisely Canada toolkit provides several approaches that encourage active patient engagement and empowerment (https://choosingwiselycanada.org/toolkit/ask-why-ppis) including patient handouts with practical information on PPIs and on GERD treatment.¹⁶

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Figure 1.

Deprescribing algorithm

Implementation

Prescription refill requests, and medication reconciliation at admission to and discharge from hospital, are opportunities to review the indication for a PPI and discuss deprescribing where appropriate. Other strategies for identifying opportunities for deprescribing may include reviewing all patients taking twice-daily PPIs or focusing on patients who are taking more than 5 medications (eg, using electronic medical record reports). Patient education strategies and academic detailing may also be promising approaches.²⁶ It is important to document the indication for long-term use for patients who require it; this is often done with input from the gastroenterologist or endoscopist. Patients should be involved in the decision and plan to deprescribe and made aware if they need to continue to take a PPI long term. Pharmacists can play a key role in discussing deprescribing opportunities with patients.

Case resolution

Based on our patient’s presentation with dominant symptoms of heartburn, GERD is the diagnosis. She was prescribed a PPI once daily for 8 weeks. She was informed that treatment was expected to be short term and her symptoms should resolve after 8 weeks. Her symptoms did resolve after 8 weeks, and she was able to stop the PPI at that time. Two months later she had a recurrence of symptoms requiring a further course of PPI for 8 weeks, which again resolved symptoms. After managing to quit smoking and avoid dietary triggers, she has remained symptom free.

Conclusion

The new Choosing Wisely Canada toolkit “Ask Why for PPIs” is a useful document to help physicians to appropriately prescribe, judiciously use, and, where appropriate, deprescribe PPIs (https://choosingwiselycanada.org/toolkit/ask-why-ppis).¹⁶