Differential Risk of Peptic Ulcer Among Users of Antidepressants Combined With Nonsteroidal Anti-inflammatory Drugs.
BACKGROUND
Selective serotonin reuptake inhibitors (SSRIs) have been reported to have an increased risk of gastrointestinal adverse events, and the risk may be further increased by combined use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, little has been known about the risk of peptic ulcer associated with other classes of antidepressants or individual antidepressants combined with NSAIDs.


METHODS
We conducted a retrospective cohort study to define the risk of peptic ulcer associated with combined use of antidepressants and NSAIDs, as compared with use of antidepressants alone. Using the Korean Health Insurance Review and Assessment Service database, we identified a total of 1,127,622 patients who began receiving antidepressants between 2009 and 2012. Propensity-based matching and Cox proportional hazards models were used to compare the risk of peptic ulcer between antidepressant users with NSAIDs and those without NSAIDs matched in a 1:1 ratio, for a total of 768,850 patients.


RESULTS
The risk of peptic ulcer did not increase with combined use of overall antidepressants and NSAIDs, as compared with antidepressant use alone (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.99-1.06). A slightly increased risk was observed for combined use of NSAIDs with tricyclic antidepressants (HR, 1.15; 95% CI, 1.09-1.21) and with SSRIs (HR, 1.08; 95% CI, 1.01-1.16).


CONCLUSIONS
We found that although concomitant use of NSAIDs and antidepressants was not associated with an increased risk of peptic ulcer for antidepressants in general, it was so for some specific classes including tricyclic antidepressants and SSRIs. However, we cannot rule out the possibility that the increased risk was solely due to NSAID use.
From the *School of Pharmacy, Sungkyunkwan University, Suwon; †Korea Centers for Disease Control and Prevention, Division of Risk Assessment and International Cooperation, Cheongju; ‡Department of Internal Medicine, Dongguk University College of Medicine, Goyang; §Department of Family Medicine, Hallym University College of Medicine, Hwasung; and Departments of ∥Psychiatry and ¶Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
Ju-Young
JY
Shin
Inmyung
I
Song
Jin-Ho
JH
Lee
Jong Lull
JL
Yoon
Jun Soo
JS
Kwon
Byung-Joo
BJ
Park
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000928:Antidepressive Agents / Q000009:adverse effects*; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010437:Peptic Ulcer / Q000139:chemically induced* / Q000453:epidemiology; D056910:Republic of Korea / Q000453:epidemiology; D012189:Retrospective Studies; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D017367:Selective Serotonin Reuptake Inhibitors