Association between SSRIs and upper gastrointestinal bleeding

Editor—The paper by de Abajo et al raises the possibility of an increased risk of upper gastrointestinal bleeding associated with selective serotonin reuptake inhibitors.1 The authors excluded patients with cancer, oesophageal varices, Mallory-Weiss disease, alcoholism, liver disease, and coagulopathies, but it is not clear if they excluded patients who were coprescribed antiulcer treatments. They do mention antecedents of upper gastrointestinal disorders as potential cofounders that were adjusted for. To investigate this issue further we examined a large prescription database provided by the general medical services in the Republic of Ireland. For November 1998 we determined the odds ratios to estimate the relative risk for the coprescription of antiulcer drugs (including H2 antagonists, proton pump inhibitors, and prostaglandin analogues but excluding antacids) with selective serotonin reuptake inhibitors and other antidepressants (table). We excluded people who were coprescribed aspirin, non-steroidal anti-inflammatory agents, or corticosteroids as this may have been cytoprotective coprescribing. This left a total of 95 929 patients for analysis, of whom 8921 received prescriptions for antiulcer drugs. There was a significant correlation between the prescribing of antidepressants of all types and antiulcer drugs. In the past, tricyclic antidepressants were used to treat peptic ulcer disease because of their antimuscarinic effects, but because of poor efficacy they are now not used for this. The newer selective serotonin reuptake inhibitors may have fewer antimuscarinic side effects, although they have gastrointestinal side effects such as vomiting, dyspepsia, and abdominal pain. Paradoxically, antidepressants (in particular, selective serotonin reuptake inhibitors) have been recommended in functional dyspepsia.2 Coprescribing of antiulcer drugs with antidepressants may indicate patients with depression who have dyspeptic symptoms, an increased prevalence of peptic ulcer disease in patients with depression, or an increased prevalence of depression in patients with peptic ulcer disease. Whatever the true association between these conditions, an increased risk of bleeding from peptic ulcer disease would be expected on the basis of these data.