FYI...Commonly used antidepressants are associated with increased risk of upper GI bleeds

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Commonly used antidepressants are associated with increased risk of upper GI

bleeds

Published date :May 31, 2010

Selective serotonin reuptake inhibitors (SSRIs) are associated with a modest but

significant increase in the risk of upper gastrointestinal (GI) bleeding,

according to a case-control analysis. In patients on an SSRI, the risk of an

upper bleed was increased 43% (odds ratio 1.43, 95% CI 1.09 - 1.89) relative to

controls. Surprisingly, SSRI therapy did not significantly increase GI risk in

patients taking NSAIDs relative to NSAIDs alone. Co-therapy with a proton pump

inhibitor (PPI) eliminated the SSRI bleeding risk.

A case-control study has associated selective serotonin reuptake inhibitors

(SSRIs) with a 43% increase in the risk of an upper gastrointestinal (GI) bleed.

Patients taking both a SSRI and a nonsteroidal anti-inflammatory drug (NSAID) do

not appear to have a significantly greater risk of an upper GI bleed than those

taking a NSAID alone. The risk of an upper GI bleed from SSRIs was characterized

as modest but potentially important for patients who already have one or more

other risk factors.

Relative to some previously published studies, this case-control analysis

" discovered a more modest association between SSRI use and upper GI bleeds,

[but] this association may still have a significant clinical impact in certain

patient groups who are already at increased risk of gastrointestinal

hemorrhage, " reported the authors, led by E. Targownik, MD. Based on the

evidence in this and other studies proton pump inhibitors (PPI) nearly

eliminated the risk of upper GI bleeds from SSRIs.

The study evaluated records from a province-wide database in Canada with almost

one million patients. Over a 12-year study period, 1,552 patients were

hospitalized for an upper GI bleed. These cases were compared to 68,590

demographically matched controls that had no history of upper GI bleeding and

were treated as outpatients during the same period as the matched patient

hospitalization. Patients and controls were considered exposed to a medication

if they had been using that medication within 14 days of the index event.

Before adjusting for confounders, those exposed to SSRI were 1.38 times more

likely to have an upper GI bleed than those who were not. After adjustment the

odds ratio (OR) rose to 1.43 (95% CI 1.09 - 1.89). Although patients using both

an NSAID and a PPI were 3.17 (95% CI 2.01 - 5.0), times more likely to have an

upper GI bleed than the case controls, the increased risk on SSRI and a NSAID

was only slightly and not significantly greater than the risk of NSAID alone (OR

1.21, 95 CI 0.76 - 1.93). The risk of upper GI bleeds did not increase with

longer duration of SSRI therapy or in patients who had not been on an SSRI

within 14 days of the bleeding event even if they had extensive exposure before.

In patients taking a SSRI and a PPI, the risk of an upper GI bleed fell below

that of the control group (OR 0.39, 95% CI 0.15 - 0.94). The reduction in risk

in those taking a PPI and both a SSRI and a NSAID was also reduced but complete

protection could not be demonstrated on a statistical basis (OR 0.29, 95% CI

0.08 - 1.03). When patients were stratified by gender, age, and presence of

other risk factors for upper GI bleeding, the protection from increased bleeding

on SSRIs with PPIs was of a similar and consistent magnitude as that for the

whole study population.

Although the increased risk of upper GI bleeding is relatively modest, the

authors emphasized that SSRIs are not only the most frequently prescribed class

of antidepressants, they are among the most frequently prescribed therapies of

any kind. In patients with a high absolute risk of bleeding, such as those with

significant medical co-morbidities taking an anticoagulant, the added risk of

SSRI may be clinically meaningful. The authors cautioned that there are no

prospective studies to provide an evidence-based, best-practice approach to

reducing risk of upper GI bleeding in patients on SSRIs, but they did conclude

this case-control analysis supports a major degree of protection from PPIs.

© AstraZeneca 2010

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