Drug-induced symptoms of functional dyspepsia and nausea. A symmetry analysis of one million prescriptions.

BACKGROUND

A large variety of drugs have been implicated in causing dyspepsia. Due to the high background incidence of dyspepsia it is impossible to distinguish between spontaneous and truly drug-related symptoms. Most patients with dyspeptic symptoms are treated empirically. Drug-induced dyspepsia might therefore be reflected in the sequencing of prokinetics relative to other medications.

OBJECTIVE

To screen a large prescription database for signs of drug-induced functional dyspepsia, applying a symmetry principle.

METHODS

Prescription data on all incident users of cisapride and metoclopramide were used to identify individuals who had started their first therapies with a prokinetic drug and an index drug within a 100-day span. A dyspepsia-provoking effect of the index drug would manifest as an excess of persons with the prokinetic drug prescribed last in this selected population. Relative to conventional analyses based on case-control or cohort design, this principle is robust to confounders that are stable over time.

RESULTS

In the cisapride analysis (1825 persons) no single drug had adjusted rate ratios significantly above unity. An inverse signal for antidepressants (rate ratio 0.57; 95% CI: 0.39-0.84) suggests that these drugs may have a therapeutic effect against functional dyspepsia. In the metoclopramide analysis (6126 persons) positive signals were found for 14 drugs, all well-known for causing nausea as a side-effect, with the exception of insulin (rate ratio 2.91, 95% CI: 1.40-8.11).

CONCLUSIONS

Drug-induced symptoms of functional dyspepsia are rare and do not contribute to the use of cisapride. The start of insulin treatment may induce nausea.