Use of SSRI, But Not SNRI, Increased Upper and Lower Gastrointestinal Bleeding

Abstract

Selective serotonin receptor inhibitor (SSRI) and serotonin-noradrenaline reuptake inhibitor (SNRI) users have been reported to have an increased risk of upper gastrointestinal bleeding (UGIB), but their association with lower gastrointestinal bleeding (LGIB) is less studied. This study aimed to analyze the incidence of UGIB and LGIB among SSRI users, SNRI users, and controls.Using the National Health Insurance Research Database of Taiwan, 9753 subjects who were taking serotonin reuptake inhibitors (8809 with SSRIs, and 944 with SNRIs), and 39,012 age, sex, and enrollment time-matched controls were enrolled at a 1:4 ratio. The log-rank test was used to analyze differences in the cumulative hazard of UGIB and LGIB between groups. Cox proportional hazard regression analysis was used to evaluate the independent risk factors for UGIB and LGIB.During the 10-year follow-up period from 2000 to 2010, SSRI users, but not SNRI users, had significantly higher incidences of UGIB and LGIB than the controls (P < 0.001; log-rank test). The use of SSRIs, but not SNRIs, was independently associated with an increased risk of UGIB (hazard ratio [HR]:1.97; 95% confidence interval [CI]: 1.67–2.31) and LGIB (HR: 2.96, 95% CI: 2.46–3.57) after adjusting for age, sex, underlying comorbidities, and medications.The long-term use of SSRIs significantly increased the risk of UGIB and LGIB, and caused more LGIB than UGIB in the general population after adjusting for possible confounding factors, but the association between SNRIs and GIB is insignificant. Further prospective studies are needed to clarify this important issue.

Risks of hospitalization for upper gastrointestinal bleeding in users of selective serotonin reuptake inhibitors after Helicobacter pylori eradication therapy: a propensity score matching analysis

“…Moreover, a high proportion (>45%) of our patients was taking gastroprotective agents, which may also affect the potential interactions. Similar findings were also reported in previous studies which did not report any significant interactions between SSRIs and other drugs …”

“…We also found that SNRIs and other antidepressants were not associated with the increased risk of UGIB, which was consistent with the study of Cheng et al The inclusion of these two control medications also addressed the concern that patients with depression may have a higher risk of peptic ulcer disease and hence the risk of UGIB rather than due to SSRIs use…”

The Safety, Tolerability and Risks Associated with the Use of Newer Generation Antidepressant Drugs: A Critical Review of the Literature

“…The overall risks are substantially higher among individuals on concomitant use of nonsteroidal anti-inflammatory agents [127,128]. The association between the use of SNRIs and upper GI bleeding is less compelling with inconsistent results across studies [129,130,131]. The role of proton pump inhibitors against this increased risk of GI bleeding when used with SSRIs has not been firmly established [15,130,132,133].…”

SSRI co‐medication with NOAC or VKA does not increase hospitalisation for bleeding: A retrospective nationwide cohort study in Austria 2010‐2015

“…19 In contrast, a previous real-world study from Texas showed a smaller number of GI-bleeding events in patients taking NOAC than those receiving VKA; however, the number of patients treated with NOAC was small. [22][23][24][25][26][27][28] However, recent studies showed that a prestroke SSRI exposure was not associated with increased cerebral haemorrhage. 18,21 Conflicting results have been reported concerning the bleeding risk of patients receiving SSRI treatment in previous observational retrospective studies, which might be explained by different applied methodologies, health care system, selection bias, or follow-up periods.…”