Researchers warn against pills that reduce stomach acid:
Many become addicted and are unable to stop

The numbers are unmistakable:

The use of proton pump inhibitors (PPIs) in Norway is steadily increasing. 

These are medications such as omeprazole (Somac) and esomeprazole (Nexium).

“There has been a fourfold increase in use over the past 20 years,” says Professor Reidar Fossmark at the Norwegian University of Science and Technology (NTNU), whose research focuses on these medications.

Today, PPIs are used by a significant proportion of the Norwegian population. According to the Norwegian Prescription Database, perscriptions were given to around 600,000 people in Norway in 2020. The number of daily doses totals to a staggering 130 million.

Something similar is also happening in many other countries, and there are no signs that this trend will level off.

What in the world is going on?

At the moment, there is no definite answer to this question. Data suggests that more people have developed reflux disease in recent decades. However, the increase in medication use likely cannot be explained solely by more people developing conditions that require treatment with proton pump inhibitors.

Guttorm Raknes is a senior physician at the Regional Medicines Information Centre (RELIS) in Northern Norway. He believes that the medications themselves may cause more and more people in the population to use them.

Increases the ability to produce acid

Proton pump inhibitors work by preventing the stomach from producing stomach acid. The substance is very effective. After just a few days, acid production is reduced by 99 per cent.

This can be an effective treatment for many acid-related health issues, such as ulcers in the stomach or oesophagus, or reflux disease with heartburn and acid reflux.

But the pills themselves can create a new problem.

Stomach acid is important for digestion. So when normal production is hindered for a long time, for example, a couple of months, the body makes changes to increase its own ability to produce stomach acid. When you then stop taking PPIs, the result is a significant increase in the amount of stomach acid.

Addictive

After stopping PPIs, there can be so much acid that even healthy people can experience unpleasant symptoms. A Danish study showed this as early as 2009.

The discomfort often becomes so great that many soon return to the pills. They have simply become addicted.

“Many of those who use proton pump inhibitors for more than four to eight weeks are unable to stop,” says Raknes.

If you stop taking the pills, acid production will decrease over time, and the symptoms will eventually go away. But it can take a long time, especially if you have used large doses or been on PPIs for a long time, Raknes notes.

“It can take weeks to months for the acid problems to go away, and this period can be very tough to get through,” he says.

A Norwegian study from 2005 showed that the stomach continued to overproduce acid for two to four months in people who had used PPIs over many years.

Vicious circle

Raknes believes that today's situation is reminiscent of the problems related to medicine-induced headaches. Some who suffer from headaches use a lot of painkillers. But the tablets themselves can cause headaches, which in turn require more medication, creating a vicious circle.

Raknes believes many doctors may not be aware that PPIs are so addictive and that they often have no plan for when patients should stop taking the pills.

Many – including doctors – can also interpret the new discomfort as a sign that the original problems are not resolved and that the medications are still needed. Although the medications are really only supposed to be taken for short periods of up to eight weeks, many probably continue with daily use for years.

The result of this may simply be that more and more people start PPI treatment, while few stop, Raknes believes.

Linked to increased risk of several diseases

Raknes believes that the use of PPIs today has created a public health problem and that we should take measures to reduce the use of these medications.

In recent years, many studies have suggested that proton pump inhibitors may be linked to diseases such as cancer, dementia, heart disease, infections, and osteoporosis.

“Although most people will not develop disease due to PPIs, there's still good reason not to use proton pump inhibitors unnecessarily,” says Raknes.

Some need PPIs

“Some patients have very good reason to use proton pump inhibitors. For these individuals, the benefits of using PPIs far outweigh the risks,” says Fossmark from NTNU.

PPIs are necessary, for example, for people with bleeding stomach ulcers, severe oesophagitis, Barrett's oesophagus, and for people at increased risk of ulcers who have to take non-steroidal anti-inflammatory drugs, which are called NSAIDs.

For these patients, discontinuing PPI medications can be dangerous.

People who have severe problems with reflux disease may also need proton pump inhibitors, Fossmark believes.

Lax doctors

Even though some really need to reduce their stomach acid levels, much of the PPI use is probably unnecessary, Raknes argues. 

“Many patients are routinely put on proton pump inhibitors as a precaution when they take certain medications or are admitted to hospital,” he says.

Not everyone with reflux disease – a very common health problem in the population – needs PPIs.

Both Fossmark and Raknes believe doctors have probably been too lax in prescribing proton pump inhibitors.

“Many doctors perceive it as harmless to try PPIs in patients with heartburn or diffuse digestive issues, without having conducted examinations to diagnose reflux disease,” says Raknes.

Paradoxically, however, several studies suggest that many of these patients do not actually benefit from PPIs.

Often fails to help with reflux disease

Many people with presumed reflux disease do not improve with PPIs, Fossmark and his colleagues concluded in a review from 2023.

Summaries of clinical trials show, for example, that proton pump inhibitors are not much better than placebo for dyspepsia, which is discomfort in the upper part of the stomach. The same applies to patients with chronic coughing and throat clearing, also called laryngopharyngeal reflux, or LPR.

Research on PPIs as a treatment for dyspepsia has shown that at least ten patients must take PPIs for just one of them to benefit from the medication.

At the same time, the pills also provide a significant placebo effect that can deceive both the patient and the doctor at first.

“Patients may start on PPIs and experience a placebo effect, but when they stop, they get a real increase in acid-related symptoms,” says Fossmark.

In reality, patients end up without benefits but with new side effects that make them continue the medication to avoid getting worse than before.

Fairly safe, but unnecessary use should be stopped

Both Raknes and Fossmark believe it is important to reduce the unnecessary use of proton pump inhibitors, while not scaring patients who genuinely need them.

“The main message is that these are fairly safe medications – but it's a problem if large sections of the population use them for no reason,” says Fossmark.

Raknes believes many struggling with acid problems can benefit from lifestyle measures such as losing weight, quitting smoking, not eating right before bedtime, and raising the head of the bed.

There are also over-the-counter acid-neutralising chewable tablets.

Would like H2 blockers

Raknes also wants more people who need help to be able to get H2 blockers on prescription. These are a type of medication that also inhibits acid production. They work faster than PPIs but are not as strong. H2 blockers are less associated with increased risk of disease anddependency than proton pump inhibitors.

However, a few years ago, there was a major scandal surrounding the H2 blocker Zantac. Questions were asked about potentially carcinogenic substances in the tablets. As a reaction to this, the medications were withdrawn from the market.

In several other countries, other H2 blockers are now available as prescription medications. It is also possible to buy H2 blockers without a prescription in Norway, although they are quite expensive.

“In Norway, it's still far too cumbersome for doctors to prescribe H2 blockers. It should be possible to prescribe them without patients having used PPIs first,” Fossmark says.

He also wants these medications to return.

"I believe there are many today who use PPIs who could use H2 blockers. They are much better suited for those who have occasional problems," says Fossmark.

References:

Fossmark et al. Adverse Effects of Proton Pump Inhibitors—Evidence and Plausibility, International Journal of Molecular Sciences, 2019. DOI: 10.3390/ijms20205203

Fossmark et al. Is empiric proton pump inhibition in patients with symptoms of extraesophageal gastroesophageal reflux justified?, BMC Gastroenterology, 2023. DOI: 10.1186/s12876-023-02945-7

Raknes, G. & Giverhaug, T. Mer om problematiske protonpumpehemmere (More about problematic proton pump inhibitors), RELIS, 2020.

Reimer et al. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy, Gastroenterology, 2009. DOI: 10.1053/j.gastro.2009.03.058

Waldum, H. & Martinsen, T.C. Uforstand å tro at biologiske funksjoner kan fjernes uten konsekvenser (Absurd to believe that biological functions can be removed without consequences), Dagens Medisin, August 2023.

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Translated by Nancy Bazilchuk

Read the Norwegian version of this article on forskning.no

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