Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: a population-based cohort study.
BACKGROUND
Selective serotonin reuptake inhibitors (SSRIs) have been suspected of increasing the risk of bleeding. We examined the risk of upper gastrointestinal tract (GI) bleeding with use of antidepressant medication.


METHODS
All users of antidepressants in the county of North Jutland, Denmark, from January 1, 1991, to December 31, 1995, were identified in the Pharmaco-Epidemiologic Prescription Database of North Jutland. In the Hospital Discharge Register, hospitalizations for upper GI bleeding were searched among the 26 005 users of antidepressant medications and compared with the number of hospitalizations in the population of North Jutland who did not receive prescriptions for antidepressants.


RESULTS
During periods of SSRI use without use of other drugs associated with upper GI bleeding, we observed 55 upper GI bleeding episodes, which was 3.6 times more than expected (95% confidence interval, 2.7-4.7), corresponding to a rate difference of 3.1 per 1000 treatment years. Combined use of an SSRI and nonsteroidal anti-inflammatory drugs or low-dose aspirin increased the risk to 12.2 (95% confidence interval, 7.1-19.5) and 5.2 (95% confidence interval, 3.2-8.0), respectively. Non-SSRIs increased the risk of upper GI bleeding to 2.3 (95% confidence interval, 1.5-3.4), while antidepressants without action on the serotonin receptor had no significant effect on the risk of upper GI bleeding. The risk with SSRI use returned to unity after termination of SSRI use, while the risks were similarly increased during periods of use and nonuse of non-SSRIs.


CONCLUSIONS
Selective serotonin reuptake inhibitors increase the risk of upper GI bleeding, and this effect is potentiated by concurrent use of nonsteroidal anti-inflammatory drugs or low-dose aspirin, whereas an increased risk of upper GI bleeding could not be attributed to other types of antidepressants.
Dalton
Susanne Oksbjerg
SO
Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark. sanne@cancer.dk
Johansen
Christoffer
C
Mellemkjaer
Lene
L
Nørgård
Bente
B
Sørensen
Henrik Toft
HT
Olsen
Jørgen H
JH
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D004357:Drug Synergism; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D018570:Risk Assessment; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000928:Antidepressive Agents; D017367:Selective Serotonin Reuptake Inhibitors