A commonly prescribed medication for chronic stomach problems doesn’t perform any better than a placebo, even when patients are genetically selected as likely to respond, a latest study reveals. The effectiveness of the treatment appears to hinge on whether patients *believe* they are receiving the active drug, rather than the drug itself.
The research, published January 13, 2026, in Clinical Gastroenterology and Hepatology, focuses on nortriptyline, a medication originally developed as an antidepressant. It’s frequently used to treat functional dyspepsia, a condition characterized by long-lasting symptoms like stomach pain, bloating, and feeling full quickly, despite a lack of identifiable physical causes. Nortriptyline is currently included in treatment guidelines as a standard option when other therapies prove insufficient.
Given inconsistent evidence supporting nortriptyline’s effectiveness and the potential for side effects, researchers at Maastricht UMC+ sought to determine if a more targeted approach to prescribing the drug could improve outcomes. The study aimed to address a long-standing debate about the treatment’s efficacy.
The study involved 33 patients who received nortriptyline and 36 who received a placebo, with neither the participants nor the researchers knowing who received which treatment. Crucially, only patients whose DNA indicated they could normally metabolize the drug were included. Individuals who process the medication too slowly – and are therefore at higher risk of side effects – were excluded from the trial.
“We thought: if this drug really works, then we should see that particularly in this carefully selected group,” explained lead researcher Daniel Keszthelyi, professor of Gastroenterology and Hepatology at MUMC+.
However, the results were surprising. Patients receiving nortriptyline did not experience a higher rate of improvement compared to those receiving the placebo. Approximately half of the participants in both groups reported symptom relief, and there was no significant difference in the number of side effects experienced. This finding highlights the complex interplay between medication, biology, and patient expectation.
While the drug didn’t demonstrate overall benefit, researchers did observe a correlation between improvement and drug levels in the blood, as well as a link to side effects. “That suggests that the drug does have a biological effect in a specific subgroup,” Keszthelyi noted, “although this study is not sufficient to demonstrate a general treatment benefit.”
What appeared to be most influential was the patient’s expectation of improvement. More than three-quarters of patients who believed they were receiving the actual medication reported feeling better, regardless of whether they received nortriptyline or the placebo.
“Whether someone feels better depends more on what they expect than on what’s actually in the pill,” Keszthelyi said. “That is the essence of the placebo effect. And that’s not a weakness, but something we can make better use of in the clinic.”
The researchers emphasize that these findings do not mean nortriptyline should no longer be prescribed. Instead, they underscore the importance of the treatment context – the conversation with the doctor, feeling heard and understood, and the sense that complaints are being taken seriously.
“The way you explain and offer a treatment is already part of the treatment,” Keszthelyi added. “In research, we try to minimize the placebo effect. In daily care, you want to harness that effect, as it helps patients.”
The study was conducted across 11 Dutch hospitals and funded by a grant from ZonMw. Keszthelyi is affiliated with the NUTRIM research institute at Maastricht University and Maastricht UMC+.
