BMJ 2001;323:655 ( 22 September )

Papers

Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort study

C van Walraven, assistant professor of medicine, ^a M M Mamdani, scientist, ^b P S Wells, associate professor of medicine, ^a J I Williams, vice president of research. ^c

^a Clinical Epidemiology Unit, Ottawa Health Research Institute, Ottawa Hospital - Civic Campus, Ottawa, ON, Canada K1Y 4E9, ^b Institute for Clinical Evaluative Sciences, Toronto, ON, Canada M4N 3M5, ^c Toronto Rehabilitation Institute, Toronto, ON, Canada M5G 2A2

Correspondence to: C van Walraven carlv{at}ohri.ca

Objectives: To determine the association between inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding.
Design: Retrospective cohort study from population based databases.
Setting: Ontario, Canada.
Participants: 317 824 elderly people observed for more than 130 000 person years. The patients started taking an antidepressant between 1992 and 1998 and were grouped by how much the drug inhibited serotonin reuptake. Patients were observed until they stopped the drug, had an upper gastrointestinal bleed, or died or the study ended.
Main outcome measure: Admission to hospital for acute upper gastrointestinal bleeding.
Results: Overall, 974 bleeds were observed, with an overall bleeding rate of 7.3 per 1000 person years. After controlling for age or previous gastrointestinal bleeding, the risk of bleeding significantly increased by 10.7% and 9.8%, respectively, with increasing inhibition of serotonin reuptake. Absolute differences in bleeding between antidepressant groups were greatest for octogenarians (low inhibition of serotonin reuptake, 10.6 bleeds/1000 person years v high inhibition of serotonin reuptake, 14.7 bleeds/1000 person years; number needed to harm 244) and those with previous upper gastrointestinal bleeding (low, 28.6 bleeds/1000 person years v high, 40.3 bleeds/1000 person years; number needed to harm 85).
Conclusions: After age or previous upper gastrointestinal bleeding were controlled for, antidepressants with high inhibition of serotonin reuptake increased the risk of upper gastrointestinal bleeding. These increases are clinically important for elderly patients and those with previous gastrointestinal bleeding.

What is already known on this topic A case-control study found that the risk of upper gastrointestinal bleeding increases with intake of antidepressants that extensively inhibit serotonin reuptake The study's validity was questioned because antidepressants were not specifically classified by the extent that they inhibit serotonin reuptake, and absolute differences in bleeding rates between antidepressants were unavailable What this study adds The risk of upper gastrointestinal bleeding in elderly and depressed patients increases with antidepressants having the greatest extent of inhibition of serotonin reuptake This increased risk of bleeding is clinically important for patients with a high risk of bleedingnamely, octogenarians and those with previous upper gastrointestinal bleeding The extent that an antidepressant inhibits serotonin reuptake should be considered when drugs are required for depression in high risk patients

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