Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study

BMJ 1999;319:1106-1109 ( 23 October )

General Practice

Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study

Editorial by Li Wan Po

Francisco José de Abajo, head, ^a Luis Alberto García Rodríguez, director, ^c Dolores Montero, head. ^b

^a División de Farmacoepidemiología y Farmacovigilancia, Agencia Española del Medicamento, 28220 Majadahonda, Madrid, Spain, ^b Safety Evaluation Unit, División de Farmacoepidemiología y Farmacovigilancia, Agencia Española del Medicamento, ^c Centro Español de Investigación Farmacoepidemiológica, Madrid, Spain

Correspondence to: F J de Abajo fabajo{at}agemed.es

Objective: To examine the association between selectiveserotonin reuptake inhibitors and risk of upper gastrointestinalbleeding.
Design: Population based case-controlstudy.
Setting: General practices included in the UK generalpractice researchdatabase.
Subjects: 1651 incident cases of upper gastrointestinalbleeding and 248 cases of ulcer perforation among patients aged40 to 79 years between April 1993 and September 1997, and 10 000controls matched for age, sex, and year that the case wasidentified.
Interventions: Review of computer profiles for all potentialcases, and an internal validation study to confirm the accuracyof the diagnosis on the basis of the computerisedinformation.
Main outcome measures: Current use of selective serotonin reuptakeinhibitors or other antidepressants within 30 days before theindexdate.
Results: Current exposure to selective serotonin reuptakeinhibitors was identified in 3.1% (52 of 1651) of patients withupper gastrointestinal bleeding but only 1.0% (95 of 10 000) ofcontrols, giving an adjusted rate ratio of 3.0 (95% confidenceinterval 2.1 to 4.4). This effect measure was not modified bysex, age, dose, or treatment duration. A crude incidence of 1case per 8000 prescriptions was estimated. A small associationwas found with non-selective serotonin reuptake inhibitors (relativerisk 1.4, 1.1 to 1.9) but not with antidepressants lacking thisinhibitory effect. None of the groups of antidepressants was associatedwith ulcer perforation. The concurrent use of selective serotoninreuptake inhibitors with non-steroidal anti-inflammatory drugsincreased the risk of upper gastrointestinal bleeding beyond thesum of their independent effects (15.6, 6.6 to 36.6). A smallerinteraction was also found between selective serotonin reuptakeinhibitors and low dose aspirin (7.2, 3.1 to 17.1).
Conclusions: Selective serotonin reuptake inhibitors increasethe risk of upper gastrointestinal bleeding. The absolute effectis, however, moderate and about equivalent to low dose ibuprofen.The concurrent use of non-steroidal anti-inflammatory drugs oraspirin with selective serotonin reuptake inhibitors greatly increasesthe risk of upper gastrointestinalbleeding.

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