ABSTRACT
BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs)
have been associated with increased risk of upper gastrointestinal
bleeding (UGIB) in older patients, but little is known about the risk
associated with individual SSRI drugs and doses.
METHODS: We conducted a nested case-control study within a
cohort of 9,295 patients aged ≥65 years treated with SSRIs from 2000 to
2013 using claims data of a universal health insurance in Taiwan.
Incident cases of UGIB during follow-up period were identified and
matched with three control subjects for age, sex, and follow-up
duration. Conditional logistic regression was used to estimate odds
ratio (OR) of UGIB associated with use of individual SSRI drugs and
cumulative dose.
RESULTS: UGIB risk increased with the increasing cumulative
doses of SSRIs (adjusted OR: 1.28, 95% confidence interval [CI]:
1.02–1.62 for the highest vs. the lowest tertile). Compared with users
of other SSRIs, Fluoxetine users were at had an increased risk of UGIB
(adjusted OR: 1.25, 95% CI: 1.03–1.50), whereas paroxetine users had
29% decreased odds (95% CI: 0.56–0.91). A dose-response manner was
observed between fluoxetine use and UGIB (adjusted OR [95% CI] for
tertiles of cumulative dose vs. use of other SSRI classes: tertile 1,
1.04 [0.78-1.39]; tertile 2, 1.25 [0.96-1.63]; tertile 3, 1.44
[1.11–1.87]). The increased risk was only observed among current
fluoxetine users.
CONCLUSIONS: Among older adults treated with SSRIs, fluoxetine
therapy was associated with increased risk of UGIB in a dose-response
manner. Careful considerations in treatment dosage are needed when
providing care to older people.
Key words: older people; selective serotonin reuptake
inhibitors; upper gastrointestinal bleeding; drug dose