The perils of proton pump inhibitors - Part 1

Rampant overprescription of PPIs continues, despite attempts to rein it in. This 3 part miniseries takes a close look at one of the biggest blockbuster drugs of all time.

Proton pump inhibitors (PPIs) are a class of medicines that include Nexium, Somac, Pariet, Prilosec, Maxor and Prevacid, and many generics. These drugs, which drastically reduce the secretion of hydrochloric acid by the stomach, are among the best-selling pharmaceuticals of all time. Australians are enthusiastic participants in the global acid-suppressing pill-popping party:

• In the 2022/23 financial year, two proton pump inhibitors - pantoprazole (Somac) and esomeprazole (Nexium) were the third and fourth most commonly prescribed drugs respectively, with nearly 19 million prescriptions issued, in a population of 26 million.

• While 15 per cent of Australians over 18 had at least one Pharmaceutical Benefit Scheme (PBS) prescription for a PPI medicine dispensed in one year, that rate is 47 per cent for people aged 75 years and over. Since conditions that decrease the secretion of stomach acid (such as atrophic gastritis) become more common as people age, this means that a significant proportion of elderly people who already have reduced gastric acid secretion, are taking drugs that further suppress their ability to make stomach acid.

• PPIs are only indicated for short-term use (4-8 weeks) for most patients, and yet 38 per cent of 75+ year olds had four or more prescriptions dispensed per year, indicating long-term use in a significant proportion of elderly people.

• These usage data do not include PPIs purchased over the counter (OTC i.e. without a doctor's prescription); the first PPI was authorised for OTC sale in 2015, and most PPIs are now available OTC in Australia, albeit with only a 7-day supply and higher cost than PBS prescriptions.

I've written about proton pump inhibitors in several other posts, including The purple pill that kills, Acid suppressors and antibiotics increase allergic disease, Drugs and gut bugs, and Depressing drugs.

But with ever more studies on the dangers of PPIs appearing in the medical literature, I thought it was high time to pull together everything you need to know about this class of drugs into one miniseries, so that you can make an informed decision about whether to continue taking one if you're already on it, or to start taking one if it's been prescribed for you.

In Part 1 of this miniseries, we'll look at how PPIs work, what they're supposed to be used for, and what is known about the extent of their overuse and inappropriate use.

In Part 2, we'll examine the known and suspected adverse effects of PPIs, and why they might occur.

Part 3 will cover how to stop taking PPIs safely, and how you might go about repairing any damage they may have caused.

PPIs: The basics

1. How do they work?

Let's start with the mechanism of action of PPIs. They block a critical chemical reaction that is required for the parietal cells of the stomach to release acid, resulting in up to 99 per cent inhibition of acid secretion. When taking a PPI, the pH of the stomach, which is normally between 1.5 and 3.5, will be higher than 4 (i.e. dramatically less acidic - or in other words, more alkaline - than normal) for most of the day.

2. What conditions are they prescribed for?

Tissues in the upper gut that have become damaged by an inflammatory reaction (for example, erosive gastritis due to an overgrowth of Helicobacter pylori in the stomach, or regurgitation of the acidic stomach contents into the oesophagus) are able to heal when acid secretion is suppressed by PPIs.

Hence, PPIs are recommended for short-term use (4-8 weeks) for the treatment of peptic ulcer (ulcers in the stomach and/or duodenum); as part of triple therapy for eradication of H. pylori; and for healing erosive oesophagitis.

In the real world though, by far the most common reason for a PPI prescription is for relief of the upper gastrointestinal symptoms of gastro-oesophageal reflux disorders (GORD, or GERD for our American cousins).

However, according to Primary Health Tasmania, only around one third of people with GORD have erosive disease. Of these, approximately 70 per cent had complete healing after taking a PPI for only 4 weeks, and 85 per cent by 8 weeks. But for the remaining two thirds of patients with non-erosive GORD (also called endoscopy negative reflux disease), the net remission rate for heartburn symptoms is only 29 per cent.

That is, if you are one of the roughly 70 per cent of people who suffers reflux but doesn't have erosions in the lining of your upper gut, taking a PPI may give you temporary symptom relief but is highly unlikely to leave you any better off. This is why clinical practice guidelines do not recommend these drugs for treatment of simple GORD.

The only valid indications for long-term use of PPIs are:

• Barrett’s oesophagus (pre-cancerous changes in the oesophagus, usually due to long-term GORD);

• Symptom management for severe oesophagitis, oesophageal stricture and/or oesophageal scleroderma;

• Those at a high risk of gastrointestinal ulceration, for example due to taking long-term nonsteroidal anti-inflammatory drugs (NSAIDs) or oral bisphosphonates;

• Healing and relapse prevention in patients with H. pylori-associated disease where eradication therapy has failed or is contraindicated;

• Healing and/or prevention of ulcers in patients with Zollinger-Ellison syndrome;

• Gastrinoma; and

• Symptom management and prevention of complications in patients with GORD who have frequent, significant symptoms that are not controlled by lower doses of PPIs, or intermittent doses of PPIs.

But even though the vast majority of Australians taking one of these drugs does not have any of the valid indications for long-term use listed above, the average duration of PPI therapy is 3.8 years.

3. What is the extent of overuse and inappropriate use?

Studies of PPI use both within Australia and internationally have consistently found

"good evidence that they are overused, that opportunities for lifestyle interventions are not maximised and that many people are inappropriately using PPI medicines for long periods of time."

The Third Australian Atlas of Healthcare Variation, Ch. 2.3: Proton pump inhibitor medicines dispensing, 18 years and over

In fact, despite multiple programs to educate doctors and patients on the correct use of these drugs, up to 84 per cent of PPIs are inappropriately used, meaning that they are either prescribed without a valid medical reason, used for too long, or used at the wrong dose.

I certainly see this in my own practice. I have seen dozens of clients who have been on a PPI for months to years, without any of the valid indications listed above. My own mother was on a PPI for many years, until my repeated insistence that her GP review her medications finally bore fruit (only after she had suffered fractures of her pelvis and femur; more on that in Part 2).

My observation is that if you walk into a doctor's office complaining of just about any symptom of gut distress, from excess burping and farting to bloating, you're likely to walk out with a prescription for a PPI.

But what's the big deal about taking a PPI if you don't need it? After all, since practically all of them are available over the counter in Australia, surely they must be pretty safe, right? Wrong. In Part 2 of this series, we'll survey the literature on adverse effects of PPIs, and what is known and suspected about why they occur.

For information on my private practice, please visit Empower Total Health. I am a Certified Lifestyle Medicine Practitioner, with an ND, GDCouns, BHSc(Hons) and Fellowship of the Australasian Society of Lifestyle Medicine.