Since PPI are also the most effective therapy in NERD, it is advisable to start treatment with these compounds. However, results from treatment in patients with NERD are much more complex. This has to be ascribed to the heterogenous population: solely based upon a careful history of symptoms it is not always possible to exclude patients with predominant non-acid reflux or aerophagia who often also report to suffer from heartburn, but who will eventually not respond to acid inhibitory drug. Thus, the outcome from an effective treatment will also generate valuable diagnostic information. Taken these facts into consideration, prompt response to PPI therapy supports the assumption that pathological reflux is the underlying pathophysiological mechanism though placebo effects cannot be excluded. On the other hand, complete failure of PPI therapy casts doubt on the suspected diagnosis of NERD.
Since acid inhibitory effects vary considerably interindividually, PPI dose should be doubled if responses to PPI therapy are unsatisfactory. The optimal intervals after which the dose escalation should be initiated is unclear so far, but should be carried out not later than 6-8 weeks after starting therapy. If doubled or tripled PPI doses (preferentially administered in divided doses which will produce profound and prolonged acid inhibition close to achlorhydria with the exception of only few patients) will not lead to disappearance of reflux symptoms, it can be concluded with almost certainty that acid reflux does not play a significant role for the symptoms. Only in rare cases, pH-metry will be necessary to confirm absence of pathological reflux (for further discussion see chapter on therapeutic failure).
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