Standard treatment for stomach complaints is no more effective than a placebo

However, the evidence for the effectiveness of nortriptyline in treating stomach complaints is not conclusive, whilst some patients experience unpleasant side effects. The researchers therefore investigated whether the drug might work better if prescribed in a more targeted manner. In the study, nortriptyline was given only to patients who, according to their DNA, metabolise the drug normally. People in whom the drug is processed too slowly – and who therefore have an increased risk of side effects – did not take part.

“We thought: if this drug really works, then we should see that specifically in this carefully selected group,” says lead researcher Daniel Keszthelyi, Professor of Gastroenterology and Hepatology at MUMC+. That is why 33 patients were given nortriptyline and 36 patients a placebo, without either them or the researchers knowing who was taking which drug. “In this way, we wanted to provide clarity on a treatment that has been the subject of debate for years.”

That expectation did not materialise. Patients who were given nortriptyline did not recover any more often than those who received a placebo. Around half of the participants in both groups showed an improvement in their symptoms. Nor was there any difference in the number of side effects between the two groups.

That does not mean the drug has no effect at all. In patients who did experience improvement with nortriptyline, higher levels of the drug were measured in the blood. There was also a link to side effects. “This suggests that the drug does indeed have a biological effect in a specific subgroup,” explains Keszthelyi, “although this study is insufficient to demonstrate a general therapeutic benefit.”

What does seem to be the decisive factor, however, is the patient’s belief. Of the patients who thought they were receiving the real medicine, more than three-quarters reported an improvement, regardless of whether they were given the medicine or the placebo.

“Whether someone feels better therefore depends more on what they expect than on what is actually in the pill,” says Keszthelyi. “That is the essence of the placebo effect. And that is not a weakness, but rather something we can make better use of in the consulting room.”

The researchers emphasise that the results do not mean nortriptyline should no longer be prescribed. However, they do highlight the importance of the context of treatment: the consultation with the doctor, being taken seriously, and the feeling that one’s symptoms are being carefully assessed.

“The way in which you explain and offer a treatment is already part of the treatment,” explains Keszthelyi. “In research, we try to minimise the placebo effect as much as possible. In everyday care, however, you want to make use of that effect, because it helps patients.”

The study was conducted in 11 Dutch hospitals and funded by a grant from ZonMw. Principal investigator Daniel Keszthelyi is affiliated with the NUTRIM research institute at Maastricht University and Maastricht UMC+.

This article was previously published on the Maastricht UMC+ website.

Did you enjoy reading this article? Follow us on Instagram and LinkedIn for more.