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 dyspep sia. Due to the high background incidence of dyspepsia it is impossible to distinguish between spontaneous and truly drug-related symptoms. Most patie nts with dyspeptic symptoms are treated empirically. Drug-induced dyspepsia might therefore be reflected in the sequencing of prokinetics relative to other medications. Aim: To screen a large prescription database for signs of drug-induced func tional dyspepsia, applying a symmetry principle. Methods: Prescription data on all incident users of cisapride and metoclopr amide were used to identify individuals who had started their first therapi es with a prokinetic drug and an index drug within a 100-day span. A dyspep sia-provoking effect of the index drug would manifest as an excess of perso ns with the prokinetic drug prescribed last in this selected population. Re lative to conventional analyses based on case-control or cohort design, thi s principle is robust to confounders that are stable over time. Results: In the cisapride analysis (1825 persons) no single drug had adjust ed rate ratios significantly above unity. An inverse signal for antidepress ants (rate ratio 0.57; 95% CI: 0.39-0.84) suggests that these drugs may hav e 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 (r ate 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.