Proton pump inhibitors (PPIs): when to take them, and when to taper off

Proton pump inhibitors (PPIs): when to take them, and when to taper off

Proton pump inhibitors - PPIs - are widely used in Denmark and worldwide. Omeprazole, esomeprazole, pantoprazole and lansoprazole inhibit the proton pump (the H+/K+-ATPase) in the stomach lining that secretes hydrochloric acid, which substantially reduces acid production. How much that helps depends on the indication: in acid-related conditions such as reflux oesophagitis and peptic ulcer, acid suppression is what allows the mucosa to heal, whereas symptoms that are not driven by acid will not necessarily improve.

PPIs work well for acid-related conditions and most people tolerate them. The problem starts when a short course becomes years of use without a clear reason. This article explains when PPIs are the right choice, what risks have been described with longer use, how the indication is reassessed, and how dose reduction or stopping is planned individually with your doctor.

---

When are PPIs the right choice?

PPIs are prescribed in conditions such as the following. Treatment length is set by the prescribing doctor based on the indication and the response, and no fixed period is given here:

• GERD (acid reflux) with documented oesophagitis or daily symptoms that don't respond to lifestyle changes and antacids.
• Peptic ulcer disease (gastric or duodenal), alone or as part of Helicobacter pylori eradication.
• Barrett's oesophagus - usually long-term maintenance.
• Gastric protection alongside NSAIDs (ibuprofen, diclofenac), aspirin or anticoagulants in patients where the doctor judges the risk of upper gastrointestinal bleeding to be increased. The assessment is individual, and there is no single fixed age cut-off.
• Zollinger-Ellison syndrome and other rare hypersecretory states.

For mild, occasional symptoms, lifestyle measures (weight loss, raised head of the bed, less coffee and alcohol, no large late-evening meals) and antacids or alginates as needed can be relevant. What is right for you depends on your symptoms, any alarm features and your doctor's assessment. PPIs are prescribed after a medical assessment of the indication.

---

What do we know about long-term use?

When gastric acid is suppressed for months or years, the absorption of certain nutrients changes. The findings below come mainly from observational studies. They show statistical associations, not proven causation, and they are vulnerable to the fact that PPI users are often older and sicker than the comparison group. The AGA points out that fear of these associations is not in itself a reason to stop a well-indicated PPI [6].

Reported association	What the studies show	Suggested mechanism (hypothesis)
B12 and calcium deficiency	Observational studies have described lower B12 and calcium levels in long-term PPI users, particularly in older people on several medicines. These are statistical associations without proven causation, and they cannot be transferred directly to younger or short-term users [3].	One suggested explanation is that gastric acid releases B12 from protein and dissolves calcium, so absorption falls during long-term suppression. The mechanism is not confirmed.
Clostridioides difficile infection	Observational studies report an association between prolonged PPI therapy and enteric infections, including C. difficile. Causality is not established, and no pooled risk figure is given here [1].	One suggested explanation is that gastric acid acts as a barrier against gut bacteria. The mechanism is not confirmed.
Bone fractures (hip, spine)	Observational studies and meta-analyses report a modest statistical association, particularly with longer-term or high-dose treatment and in older adults. The results are heterogeneous, do not in themselves show causation, and there is no universal duration threshold at which the risk begins [1,3].	Suggested explanations include reduced calcium absorption and effects on parathyroid hormone. Neither is confirmed.
Chronic kidney disease	Renal effects, including acute interstitial nephritis and chronic kidney disease, are described in observational studies of long-term use. The size of the risk is uncertain and is not given as a figure here [5].	Allergic interstitial nephritis is described and can become chronic if missed. How this relates to chronic kidney disease is unsettled.
Magnesium deficiency	May cause cramps, arrhythmias and fatigue.	One suggested explanation is reduced intestinal absorption. The mechanism is not confirmed and there is no reliable time threshold.

These findings should be weighed against the alternative: untreated reflux oesophagitis can lead to stricture, Barrett's oesophagus and rarely adenocarcinoma, and an untreated peptic ulcer can bleed or perforate. PPIs remain the right choice for many. The point is that the treatment must be reviewed regularly, not renewed on autopilot.

---

Deprescribing

The decision to continue or stop a PPI is based on the original indication and your risk of upper gastrointestinal bleeding - not on worry about observational studies [6]. If the indication has gone (the ulcer has healed, the NSAID course is finished, reflux symptoms have been absent for a longer period with no other reason to continue), tapering can be discussed with your doctor. Symptom relief alone is not enough: in severe oesophagitis, Barrett's oesophagus or ongoing anticoagulation with a high bleeding risk, the PPI is often continued even if you feel nothing.

There is no mandatory universal taper. Gradual dose reduction, switching to on-demand use and stopping outright can all be considered, and the choice depends on dose, duration and symptoms [6]. Whichever route is chosen, be aware of rebound acid hypersecretion: the stomach may produce extra acid for a few weeks after stopping, so heartburn can flare temporarily without meaning the disease is back. Antacids or an alginate as needed can cover that period, and lifestyle measures help.

Some situations argue for continuing treatment, for example when the original indication is still present, or when the doctor judges that the risk of gastrointestinal bleeding is increased. Whether and how treatment can be tapered is therefore an individual clinical decision [6]. Never stop prescribed medicine on your own.

---

What to watch for

• Don't take PPIs without a reason. If you use an acid-suppressing medicine for occasional heartburn, follow the package instructions and the advice from your pharmacy. If the need becomes daily or persistent, have it assessed by a doctor rather than carrying on unsupervised.
• Never stop a prescribed PPI without agreeing it with your treating doctor, including after reading about possible long-term effects.
• Take alarm symptoms seriously. Black tarry stool, haematemesis, weight loss, swallowing difficulty or iron deficiency need investigation, not more PPI.
• Blood tests when indicated, not as routine. B12, ferritin, calcium, magnesium and kidney function are checked if you have symptoms or risk factors - not as blanket screening of every PPI user [6].
• Don't stack acid suppressants yourself. Whether an H2 blocker should be added to a PPI is a clinical decision.

---

Assessment and follow-up at Kirurgen.dk

If you have been on a PPI for a prolonged period without an agreed follow-up, or your symptoms persist despite treatment, we can help. We offer outpatient oral and nasal gastroscopy, which on independent medical indication may include biopsy and testing for Helicobacter pylori. The current waiting time for non-urgent patients with no suspicion of cancer is approximately 6-8 weeks. Waiting times can vary. On the basis of that assessment, you and your doctor can decide whether the PPI should continue, be adjusted or be tapered off.

See also: GERD reflux, peptic ulcer disease, Helicobacter pylori, Barrett's oesophagus, black stool.

---

References

1. Andrawes M, Andrawes W, Das A, Siau K. Proton Pump Inhibitors (PPIs) - An Evidence-Based Review of Indications, Efficacy, Harms, and Deprescribing. Medicina (Kaunas) 2025;61(9):1569. doi:10.3390/medicina61091569 PubMed
2. Kim SY, Lee KJ. Potential Risks Associated With Long-term Use of Proton Pump Inhibitors and the Maintenance Treatment Modality for Patients With Mild GERD. J Neurogastroenterol Motil 2024;30(4):407-420.
3. Shahid MS, Ahmed N, Kamal Z, et al. A Systematic Review of Long-Term Use of Proton Pump Inhibitors (PPIs) in Older Adults on Polypharmacy: Do PPIs Deplete Nutrients? Cureus 2025;17(8):e90888. doi:10.7759/cureus.90888 PubMed
4. Shanika LGT, et al. Proton pump inhibitor use: systematic review of global trends and practices. Eur J Clin Pharmacol 2023;79(9):1159-1172.
5. Maideen NMP. Adverse Effects Associated with Long-Term Use of Proton Pump Inhibitors. Chonnam Med J 2023;59(2):115-127. doi:10.4068/cmj.2023.59.2.115 PubMed
6. Targownik LE, Fisher DA, Saini SD. AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review. Gastroenterology 2022;162(4):1334-1342. doi:10.1053/j.gastro.2021.12.247