A commonly prescribed medication for chronic stomach complaints offers no more relief than a placebo, even when patients are genetically screened to identify those most likely to benefit, according to a new study from Maastricht University Medical Centre+ (MUMC+). The research, published in Clinical Gastroenterology and Hepatology, challenges conventional treatment approaches for functional dyspepsia, a condition characterized by persistent stomach pain, bloating and a feeling of fullness without a clear physical cause.
The medication, nortriptyline, originally developed as an antidepressant, is frequently used to manage functional dyspepsia when other treatments fail. Researchers sought to determine if tailoring its prescription based on a patient’s ability to metabolize the drug – specifically, focusing on individuals with normal CYP2D6 enzyme activity – would improve efficacy and reduce side effects. The study involved 33 patients receiving nortriptyline and 36 receiving a placebo, with neither patients nor researchers aware of who received which treatment.
Despite the genetic pre-selection, the study yielded a surprising result: patients receiving nortriptyline did not experience a greater improvement in symptoms 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 incidence of side effects between the two groups.
“We thought: if this drug really works, then we should notice that precisely in this carefully selected group,” said lead researcher Daniel Keszthelyi, professor of Gastroenterology and Hepatology at MUMC+. Though, the data did indicate a biological effect within a specific subgroup. Patients who *did* experience improvement with nortriptyline showed higher levels of the drug in their bloodstream, and a correlation with reported side effects, suggesting the medication is not entirely inert.
The study’s most significant finding centered on the power of patient expectation. More than three-quarters of patients who believed they were receiving the active medication reported improvement, regardless of whether they actually received nortriptyline or the placebo. “Whether someone feels better depends more on what they expect than on what is actually in the pill,” Keszthelyi explained. “That is the essence of the placebo effect. And that is not a weakness, but something One can build better use of in the clinic.”
Researchers emphasize that the findings do not necessitate abandoning nortriptyline as a treatment option. Instead, they highlight the critical importance of the therapeutic context – the doctor-patient interaction, feeling heard and understood, and a sense of careful consideration. “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 because it helps patients.”
The research was conducted across 11 Dutch hospitals and funded by a grant from ZonMw, the Netherlands Organisation for Health Research and Development. Keszthelyi is affiliated with the NUTRIM research institute at Maastricht University and MUMC+. Further research is needed to fully understand the mechanisms underlying the placebo response and how to best integrate it into clinical practice.
