Introduced in the 1970s for use in reducing gastric acid production, proton pump inhibitors (PPIs) are among the most widely sold drugs in the world; omeprazole appears on the World Health Organization Model List of Essential Medicines. They are used in treating conditions such as gastroesophageal reflux disease (GERD), dyspepsia, reflux esophagitis, peptic ulcer disease (PUD), and hypersecretory conditions (e.g., Zollinger-Ellisson Syndrome), and are included as part of the eradication therapy for Helicobacter pylori bacteria (Cochrane Database of Systematic Reviews 2015, Issue 11. Art. No. CD011969. doi: 10.1002/14651858.CD011969).
PPIs are also commonly used on a long-term basis for preventing esophagitis caused by laryngopharyngeal reflux (LPR). PPIs are effective at reducing gastric acid, but researchers have noted the potential for harm that comes from long-term prescription-level use, including an increased risk of bone fractures not found with short-term, low-dose use. The U.S. Food and Drug Administration included a warning on PPI drug labels in 2010, noting that the available data show that patients at the highest risk for fractures received high doses of prescription PPIs and/or used a PPI for one year or more, but decided against adding a warning label to over-the-counter versions.
Alongside an increase in bone fracture risk, long-term high-dose PPIs carry other risks, including the possibility of interference with the absorption of iron, calcium, magnesium and vitamin B-12 due to a reduction in the breakdown of micronutrients released by gastric acid (Curr Gastroenterol Rep. 2010;12: 448–457). Long-term use has also been associated with an increased risk of pneumonia and Clostridium difficile colitis, according to the Cochrane Report.
This raises an important question for clinicians who see patients with LPR: How do you assess whether a patient should be on PPIs on a long-term basis, and how do you wean them off of the medication if necessary?
As PPI use becomes ever more common, it is important to note that some patients may not need them as part of a regular regimen—a recent study noted that up to 50% of PPI users are inappropriately prescribed the medication (Ann Pharmacother. 2015;49:29-38).
Part of the problem is that while LPR symptoms differ from GERD symptoms in that LPR doesn’t usually include heartburn and regurgitation, the symptoms that are most frequently reported in LPR (mild hoarseness and the need to clear the throat, globus, post-nasal drip, chronic cough, difficulty swallowing, sore throat, and an irritated, swollen larynx) are nonspecific and may be due to other factors such as allergy, smoking, environmental irritants, infection, or vocal abuse (Am J Otolaryngol. 2016;37:245-250). The researchers who conducted the study reported on in Annals of Pharmacotherapy also noted that 22% to 70% of patients who are prescribed a PPI do not have an appropriate indication for it.
The term for weaning patients off of medication is “deprescribing,” a process that involves slowly withdrawing and stopping the medication. “Unfortunately, there really isn’t much information in terms of a ‘gold standard’ on what weaning protocols are the most effective,” said Karla O’Dell, MD, assistant professor of clinical otolaryngology at the University of Southern California Voice Center in Los Angeles. “Anecdotally, I think most use a de-escalation approach: If a patient is on a maximum dose twice a day, you would decrease the dose, then go from twice a day to once a day. Some physicians will transition patients from a PPI to an H2 blocker, and then stop completely.”
Because there is no cut-and-dried diagnostic for LPR, some physicians use a PPI as a sort of diagnostic test. But we don’t always think about getting patients back off of the PPI if that test fails. —Karla O’Dell, MD
Several studies have looked at ways to wean patients off of PPI therapy. Clark Rosen, MD, a professor of otolaryngology at the University of Pittsburgh School of Medicine in Pittsburgh, and his colleagues presented a retrospective review at the 2016 Triological Society meeting at the Combined Otolaryngology Spring Meetings (COSM) in Chicago. Thirty-seven patients with suspected LPR were instructed to wean from PPI using a standardized weaning protocol after successful treatment of their symptoms. Twenty-two of the 37 patients (59%) remained symptom free after deprescription. Fifteen patients (41%) had symptom recurrence, and 12 (32%) needed to go back on a PPI. The researchers also found that high body mass index was predictive of a failure to wean off the medication.
A recently published retrospective cohort examined 188 patients treated for LPR between April 1, 2011, and April 30, 2014, at the Queens Hospital Center Otolaryngology Clinic in New York City (Am J Otolaryngol. 2016;37:245-50). The clinic had instituted a standardized clinical protocol for LPR diagnosis and management in 2012, involving diagnosis using clinical judgment guided by the Reflux Symptom Index and Reflux Finding Score, treatment with PPIs, and weaning therapy after symptom resolution. This allowed the researchers to distinguish between patients who had been treated through the protocol and those who had not. The primary outcome measure was complete response to therapy and the secondary outcome measures were any response (complete or partial) and successful wean off PPI therapy.
The patients who were treated with the LPR protocol had higher rates of complete response, although there was no statistically significant difference in rates of any response (complete or partial) between the two groups, and were more likely to be successfully weaned off of PPI therapy than those who were not treated following the protocol. The 12-month wean rate was 52% for patients treated with the protocol versus 23% for patients treated without.
The aim of a prospective study published in 2015 was to assess the feasibility of a patient-centered deprescribing process in a population of adults with complex polypharmacy (Ann Pharmacother. 2015;49:29-38). The patient-centered deprescribing process consisted of five steps:
- Collecting a comprehensive medication history;
- Identifying potentially inappropriate medications;
- Determining whether the medication could be discontinued;
- Planning the withdrawal regimen, tapering where necessary; and
- Providing monitoring, support, and documentation.
Fifty-seven PPI users were recruited; participants were 70 (± 14) years old and took 14 (± 6) medications. Indication for use was verified in 43 participants and judged as potentially inappropriate in 19; eight of those were suitable for trial withdrawal, and six consented. All six successfully discontinued or reduced their PPI use, which was sustained at six months out in four participants.
Barriers to Deprescribing
Although deprescribing has been successful in many studies, there are some barriers to successfully implementing this strategy in a clinical practice. Some physicians prefer to continue prescribing PPIs regardless of actual indications, and many patients who might do well without PPIs put pressure on physicians to keep prescribing them. The lack of clear weaning guidelines and the fear of withdrawal or rebound symptoms are key concerns for both. (Rebound acid hypersecretion following PPI discontinuation can lead to increased stomach acid production, beginning the cycle again.)
Reeve and colleagues found that although participants accepted the weaning protocol, the time required for accessing complete medical histories and assessing follow-up conditions made the process difficult to manage during regular medical consultations.
Patient lifestyle choices present one barrier to deprescription. “Patient lifestyle changes can affect LPR symptoms—eating late at night and coffee consumption, for instance. But adopting lifestyle modifications is difficult,” said Dr. O’Dell. “These modifications become an issue in how successful weaning will be. I think more patients would be able to come off of the medication if they were able to make and sustain lifestyle modifications.”
“In addition, as physicians we can get into a pattern where if patients are doing well, we prescribe the same medications, regardless of actual need; we don’t know that LPR really needs lifelong treatment,” she added. “Because there is no cut-and-dried diagnostic for LPR, some physicians use a PPI as a sort of diagnostic test. But we don’t always think about getting patients back off of the PPI if that test fails. I think it’s probably worthwhile to try to wean them off and see if the PPIs are what’s really helping to improve their symptoms.”
The bottom line may be to treat patients with LPR with the same approach now recommended for patients with chronic sinusitis and antibiotics: Assess the situation for whether the medication is needed, prescribe when symptoms truly warrant it, and provide an endpoint where possible once symptoms have resolved.
Overall, PPIs are considered very safe medications,” said Dr. O’Dell, “but because of those potential side effects I think if patients don’t need to be on the medication long term, it’s better to wean them off of it.”
Amy E. Hamaker is a freelance medical writer based in California.