Does concurrent prescription of selective serotonin reuptake inhibitors and non-steroidal anti-inflammatory drugs substantially increase the risk of upper gastrointestinal bleeding?
BACKGROUND
A 15-fold increased risk of gastrointestinal bleeding has been reported with concurrent use of selective serotonin reuptake inhibitors and non-steroidal anti-inflammatory drugs. Recent guidance cautions against concurrent prescription, particularly in older people.


OBJECTIVE
To quantify the risk of gastrointestinal bleeding associated with current exposure to non-steroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, and both drugs concurrently.


METHODS
We conducted a case-control analysis of 11,261 cases with upper gastrointestinal bleeding and 53,156 controls matched by gender, age and general practice from computerized primary care data. We coupled this with self-controlled case series analysis.


RESULTS
Both drugs were associated with a twofold increased risk of gastrointestinal bleeding (odds ratio =2.38, 95% confidence interval 2.08-2.72 for selective serotonin reuptake inhibitors and odds ratio = 2.15, 95% confidence interval 2.02-2.28 for non-steroidal anti-inflammatory drugs). This increased risk was marginally higher for concurrent prescription (odds ratio = 2.93, 95% confidence interval 2.25-3.82). The self-controlled analysis showed a greater incidence rate ratio for gastrointestinal bleeding with non-steroidal anti-inflammatory drugs (2.71, 95% confidence interval 2.51-2.91) and lower incidence rate ratio with selective serotonin reuptake inhibitors (1.71, 95% confidence interval 1.48-1.98). The incidence rate ratio when both drugs were combined was 3.25, 95% confidence interval 1.95-5.42. Estimates were similar after restricting to people over 80 years of age. Increased risk of gastrointestinal bleeding was not specifically related to class of non-steroidal anti-inflammatory drugs and was similar when we looked at tricyclic anti-depressants.


CONCLUSIONS
Our study suggests that the risk of gastrointestinal bleeding is not substantially increased when non-steroidal anti-inflammatory drugs and selective serotonin reuptake inhibitors are prescribed together, compared with their use alone.
Tata
L J
LJ
Epidemiology and Public Health, University of Nottingham, City Hospital, Nottingham, UK. laila.tata@nottingham.ac.uk
Fortun
P J
PJ
Hubbard
R B
RB
Smeeth
L
L
Hawkey
C J
CJ
Smith
C J P
CJ
Whitaker
H J
HJ
Farrington
C P
CP
Card
T R
TR
West
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects*; D016022:Case-Control Studies; D015897:Comorbidity; D004347:Drug Interactions; D004739:England / Q000453:epidemiology; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019338:Polypharmacy; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects; D014852:Wales / Q000453:epidemiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018687:Antidepressive Agents, Second-Generation; D017367:Selective Serotonin Reuptake Inhibitors