BMJ  2008;336:2-3 (5 January), doi:10.1136/bmj.39406.449456.BE

Editorials

Overprescribing proton pump inhibitors

Is expensive and not evidence based

Proton pump inhibitors are one of the most frequently prescribed classes of drug in the world because they combine a high level of efficacy with low toxicity. In 2006, expenditure on these drugs was £425m (595m; $872m) in England¹ and £7bn globally.² Yet studies consistently show that proton pump inhibitors are being overprescribed worldwide in both primary and secondary care.^3456789 Between 25% and 70% of patients taking these drugs have no appropriate indication. This means that, at the very least, £100m from the National Health Service (NHS) budget and almost £2bn worldwide is being spent unnecessarily on proton pump inhibitors each year.

The first generic proton pump inhibitor (omeprazole) was introduced in 2002 and now comprises more than four fifths of all prescriptions for proton pump inhibitors in the United Kingdom. In the five years since the introduction of omeprazole, precriptions for proton pump inhibitors have doubled, although the reasons for the this rise are not obvious.¹ Despite this substantial increase in drug usage, the decrease in price means that overall expenditure on proton pump inhibitors has been falling in recent years.

Effective and less expensive alternative drugs, such as H₂ receptor antagonists are available for many patients. Yet prescriptions for proton pump inhibitors have superseded those for all other acid inhibiting agents and now account for over 90% of the NHS drug budget for treating dyspepsia.¹ Proton pump inhibitors cost more than other agents, which is partly why prescribing guidelines have been drafted in several countries. The National Institute for Health and Clinical Excellence (NICE) published its guidelines on proton pump inhibitors in 2000. Its recommendations for using these drugs—particularly in the long term—are relatively selective.¹⁰ If prescriptions were restricted to the recommended indications, expenditure on proton pump inhibitors would be far less than 90% of the total dyspepsia drug budget. But what is the evidence that well established guidelines are not followed?

Although it might be assumed that overprescribing occurs mainly in primary care, evidence of inappropriate use of proton pump inhibitors in secondary care is abundant. In hospital inpatients taking proton pump inhibitors in Australia,³ Ireland,⁴ and the UK,⁵ 63%, 33%, and 67% of patients did not meet their country’s criteria for taking the drug. In a series of hospital inpatients in Michigan, USA, 20% of patients were taking a proton pump inhibitor on admission and another 40% were prescribed the drug during their hospital stay (mostly for prophylaxis). At discharge, half the patients were taking a proton pump inhibitor—more than double the number who were taking the drug when admitted.⁶ In this study, 90% of patients did not need to take these drugs unless having gastro-oesophageal reflux at some time in the past is accepted as a reasonable indication.

Problems have been identified at the interface between primary and secondary care. A study from New Zealand found that 40% of hospital inpatients were taking proton pump inhibitors inappropriately.⁷ Two thirds of these patients were still taking the drugs on discharge and most were still taking them six months later. In a UK centre, the suggested length of treatment with a proton pump inhibitor was specified in fewer than one hospital discharge letter in five.⁵ Only a third of letters indicated a date for the prescription to be reviewed and only half specified why the drug was started.

Studies in primary care have come largely from Europe. In a Swedish cohort of patients who had been taking proton pump inhibitors for four years, 27% were able to discontinue the drug altogether.⁸ A prospective audit of a series of patients admitted as a medical emergency to a hospital in Wales found that a quarter of patients were taking a proton pump inhibitor. In only half of the patients was the indication for the drug deemed appropriate.⁹ The audit was repeated six months after the NICE guidelines were disseminated to local practitioners. This repeat audit found that the same proportion of admitted patients were taking a proton pump inhibitor and again that only half of these had a recommended indication.

Proton pump inhibitors have been a tremendous therapeutic advance. Especially in the long term, they have transformed the lives of patients with previously intractable symptoms of gastro-oesophageal reflux with its associated complications, and they have also proved valuable for patients who are at risk of iatrogenic upper gastrointestinal pathology. A short term trial of a proton pump inhibitor is also a good option for treating a wide range of acid-peptic conditions. But the drugs are clearly being overused.

Some people will point to their combination of superior efficacy and high safety as a justification for using them in preference to drugs such as H₂ receptor antagonists. Yet, side effects should not be overlooked. An increase in the prevalence of pneumonia and Campylobacter enteritis is reported, as well as a doubling of the risk of infection with Clostridium difficile.¹¹ Acute interstitial nephritis and osteoporosis are unusual but recognised consequences of treatment with proton pump inhibitors.¹² Such effects are fortunately rare. The adverse effect of overprescription on drug budgets around the world is the real problem. Quite how to motivate doctors to follow guidelines is a matter of considerable importance.

¹ Department of Gastroenterology, King’s College Hospital, London SE5 9RS

---

Competing interests: None declared.

Provenance and peer review: Commissioned; externally peer reviewed.

References

1. National Health Service. PACT centre pages. Drugs for dyspepsia. 2006. www.ppa.nhs.uk//news/pact-082004.htm.
2. IMS Health Report. Leading therapy classes by global pharmaceutical sales. 2006.http://www.imshealth.com/ims/portal/front/articleC/0,2777,6025_80528184_80530441,00.html.
3. Naunton M, Peterson GM, Bleasel MD. Overuse of proton pump inhibitors. J Clin Pharm Ther 2000;25:333-40.[CrossRef][ISI][Medline]
4. Mat Saad AZ, Collins N, Lobo MM, O’Connor HJ. Proton pump inhibitors: a survey of prescribing in an Irish general hospital. Int J Clin Pract 2005;59:31-4.[Medline]
5. Walker NM, McDonald J. An evaluation of the use of proton pump inhibitors. Pharm World Sci 2001;23:116-7.[CrossRef][ISI][Medline]
6. Pham CQD, Regal RE, Bostwick TR, Knauf KS. Acid suppressive therapy use on an inpatient internal medicine service. Ann Pharmacother 2006;40:1261-6.[Abstract/Free Full Text]
7. Grant K, Al-Adhami N, Tordoff J, Livesey J, Barbezat G, Reith D. Continuation of proton pump inhibitors from hospital to community. Pharm World Sci 2006;28:189-93.[CrossRef][ISI][Medline]
8. Bjornsson E, Abrahamsson H, Simren M, Mattsson N, Jensen C, Agerforz P, et al. Discontinuation of proton pump inhibitors in patients on long term therapy: a double blind, placebo controlled trial. Aliment Pharmacol Ther 2006;24:945-54.[CrossRef][ISI][Medline]
9. Batuwitage B, Kingham JCG, Morgan NE, Bartlett RL. Inappropriate prescribing of proton pump inhibitors in primary care. Postgrad Med J 2007;83:66-8.[Abstract/Free Full Text]
10. National Institute for Clinical Excellence. Guidance on the use of proton pump inhibitors (PPI) in the treatment of dyspepsia. 2000. www.nice.org.uk/newsevents/pressreleases/pressreleasearchive/pressreleases2000/2000_022_nice_issues_guidance_on_proton_pump_inhibitors_ppi_for_dyspepsia.jsp.
11. Dial S, Delaney J, Barkun A, Suissa S. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA 2005;294:2989-95.[Abstract/Free Full Text]
12. Yang Y, Lewis J, Epstein S, Metz D. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA 2006;296:2947-53.[Abstract/Free Full Text]

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