4.3 Limitations of the study
There are several limitations in our study. First, drug adherences were
unmeasurable in claims data, which can result in misclassification of
exposure levels. Although we defined SSRIs by at least two prescriptions
to reduce the possibility of including patients who never took the drugs
in the first prescription, accurate information on medication use should
be further confirmed by patients themselves. Second, older adults with
obscure GIB might be misclassified into the control group because an
obscure GIB can only be verified by endoscopic and radiologic
evaluation[39]. This could result in the underestimation of the
association in our study. Third, to improve the likelihood of
identifying patients who truly had UGIB, patients with UGIB treated only
in outpatient clinics were not included in our analysis. Therefore, our
findings may only apply to patients with severe UGIB requiring
hospitalization. Fourth, the statistical power may be insufficient to
detect mild or moderate associations in dose analysis of some classes of
SSRIs such as fluvoxamine and escitalopram, as the number of patients in
each category was small.
In conclusion, among the adults aged ≥65 years receiving SSRI
treatments, fluoxetine therapy was associated with increased risk of
UGIB in a dose-response manner. Moreover, recent users of fluoxetine
(<1 month before UGIB occurrence) had higher risk of UGIB than
those who used this medication one month ago. Further investigations are
needed to clarify whether paroxetine may incur lower risk of UGIB than
other classes of SSRIs and the possible underlying causes. As SSRI use
increases with age, physicians should accurately evaluate the patients
for risk of gastrointestinal bleeding and calculate the total doses of
SSRIs in long-term users because UGIB risk may increase with cDDDs.
Careful considerations in treatment dosage and close monitoring are
needed when providing care to older people.