I read with interest the guidance provided in Best Practice Journal on the management
of dyspepsia and heartburn in general practice (BPJ 34, Feb 2011).
I note that much of this article also applies to the management of dyspepsia and heartburn in community pharmacy. I
also note some variation in your advice from that provided in the New Zealand Guideline Group's best practice, evidence-based
Management of Dyspepsia and Heartburn guideline (2004).
Most notably, bpacnz advocates the use of a proton pump inhibitor (PPI) as first-line therapy in undifferentiated
and functional dyspepsia, though the strength of evidence to support this approach is not immediately obvious. In contrast
the NZGG guideline recommends treating according to symptoms, and recognises that undifferentiated and functional dyspepsia
without symptoms of reflux may well respond better to a prokinetic agent, rather than an acid suppressant.
I'm conscious that the NZGG guideline and my knowledge of this area is somewhat dated and I'd be keen to learn of any
advances in evidence to support PPI as a first-line therapy option in the management of undifferentiated and/or functional
Andrew Orange, Pharmacist
In the 2007 article about dyspepsia (BPJ 4, Apr 2007), the faecal
antigen test for H.Pylori was considered to have far better sensitivity and specificity than serology and was
the recommended test but in the 2011 article (BPJ 34, Feb 2011) serology
is preferred - why?
Also in the 2007 article, for dyspepsia without heartburn the NNT
for ranitidine was lower than the NNT for PPI, so why are you now recommending to use PPI as a first-line in patients
with dyspepsia without heartburn?
Also could you please comment on the cardiac safety of domperidone and what to be aware of when prescribing this?
Dr Daniel Then, GP
Proton Pump Inhibitors (PPI)
In the article “Managing dyspepsia and heartburn in general
practice – an update” (BPJ 34, Feb 2011) proton pump inhibitors (PPI) are recommended as first-line treatment
in undifferentiated and functional dyspepsia, i.e. dyspepsia which has either not been investigated in a low risk patient,
or dyspepsia that has been investigated with no underlying pathology found.
Since the New Zealand Guidelines Group guideline for the Management of dyspepsia and heartburn was published in 2004,1 there
has been an evidence based shift in practice that favours the use of PPIs as first-line therapy. This is because there
is increasing evidence that PPIs are more effective in their ability to resolve the symptoms of dyspepsia than H2 receptor
antagonists.2,3,4,5,6 Although not expressed as NNTs, this evidence shows consistent statistically significant
benefits for the empiric use of PPIs. The Cochrane reviews (and NNTs) quoted in the 2007 article have been withdrawn
from publication because the conclusions have changed and an updated Cochrane review is awaited.7 The availability
of generic PPIs has also removed the previous cost benefit of H2 receptor antagonists.
The efficacy of prokinetic agents such as domperidone and metoclopromide has been debated in the recent literature.5,8 Prokinetic
agents are no longer recommended for first line therapy because of their potential for adverse effects and the evidence
for their effectiveness is limited.2,5,9,10
Empiric treatment with PPIs in undifferentiated and functional dyspepsia therefore is favoured in evidence based guidelines
that have been produced since the 2004 New Zealand guideline.9,11,12 In addition, the use of PPIs as first-line
therapy is only one step in the suggested approach for the treatment of undifferentiated dyspepsia given in the article.
The suggested approach includes:
- The need to rule out the possibility of serious disease
- Consideration of the need for H. pylori testing
- Monitoring the response to empiric treatment so that other medicines or further investigations can be initiated
if there is no response to PPI treatment
Serology or faecal antigen test?
Each of the available tests for H. pylori has advantages and disadvantages, hence the recommendation that
the choice should be determined by the clinical setting. Carbon-13 urea breath test is the most accurate test but is
not consistently available to general practice. Serology is more convenient to obtain for both the GP and patient and
can determine whether the patient has been exposed to the infection. If infection is present and treatment is given,
the faecal antigen test, which is able to detect active infection, can be used to test cure.
Testing for H. pylori is also best determined by the likely prevalence of H. pylori in the community.
It is recommended to consider testing for H.pylori when there is a local prevalence rate of greater than 30%
(when serology tests are appropriate).
For further information about H. pylori testing, see “
pylori testing: Serology and stool antigen testing” Best Tests (March, 2010).
Safety concerns with domperidone
Domperidone has been associated with rare reports of serious ventricular arrhythmia, QT prolongation and sudden cardiac
death. In most cases, these events have occurred in patients who have had other cardiac risk factors, or in patients
who received domperidone intraveneously.7 The use of domperidone therefore should be avoided in patients
who may be at increased risk of QT prolongation such as those with hypokalaemia, severe hypomagnesaemia or structural
heart disease. It should also be used with caution in patients who are taking other drugs that may also cause QT prolongation,
such as oral ketoconazole, fluconazole, erythromycin and amiodarone.10
- New Zealand Guidelines Group (NZGG). Management of dyspepsia and heartburn. NZGG, Wellington, 2004.
- National Institute for Health and Clinical Excellence (UK). Clinical Knowledge Summaries (CKS). Dyspepsia. Available
from: www.cks.nhs.uk (Accessed April, 2011).
- Peura DA, Gudmundson J, Siepman N, et. al. Proton pump inhibitors: Effective first-line treatment for management
of dyspepsia. Dig Dis Sci 2007;52:983-7.
- Armstrong D, Veldhuyzen van Zanten SJO, Barkun AN, et.al. Heartburn dominant, uninvestigated dyspepsia: a comparison
of ‘PPI-start’ and ‘H2-RA-start’ management strategies in primary care – the CADET-HR Study. Aliment Pharmacol
- Harman RC, Peura DA. Evaluation and management of dyspepsia. Ther Adv Gastroenterol 2010;3(2):87-98.
- Nagahara A, Asaoka D, Hojo M, et al. Observational comparative trial of the efficacy of proton pump inhibitors
versus histamine-2 receptor antagonists for uninvestigated dyspepsia. J Gastroenterol Hepatol 2010;25(Suppl 1):S122-S128.
- Moayyedi P, Shelly S, Deeks JJ, et.al. WITHDRAWN: Pharmacological interventions for non-ulcer dyspepsia. Cochrane
Database Syst Rev. 2011 Feb 16;2:CD001960.
- Kandulski A, Venerito M, Malfertheiner P. Therapeutic strategies for the treatment of dyspepsia. Expert Opin Pharmacother.
- National Institute for Health and Clinical Excellence (NICE). Dyspepsia: management of dyspepsia in adults in primary
care (amended NICE guideline). NICE, 2005. Available from: www.nice.org.uk (Accessed
- Janssen-Cilag (New Zealand) Ltd. Motilium. Medicine Data Sheet. Available from:
www.medsafe.govt.nz (Accessed April 2011)
- Talley NJ, Vakil N, Practice parameters committee of the American College of Gastroenterology. Guidelines for the
management of dyspepsia. Am J Gastroenterol 2005;100(10):2324-37.
- Veldhuyzen van Zanten SJO, Bradette M, Chiba N, et al. Evidence-based recommendations for short- and long-term
management of uninvestigated dyspepsia in primary care: An update of the Canadian Dyspepsia Working Group (CanDys)
clinical management tool. Can J Gastroenterol. 2005;19(5):285-303.