Meta-analysis of the Risk of Upper Gastrointestinal Hemorrhage with Combination Therapy of Selective Serotonin Reuptake Inhibitors and Non-steroidal Anti-inflammatory Drugs

Abstract

It is thought that both selective serotonin reuptake inhibitors (SSRIs) and non-steroidal anti-inflammatory drugs (NSAIDs) can cause the adverse reaction of upper gastrointestinal hemorrhage (UGIH). To evaluate differences in the probability of UGIH occurring when SSRIs, NSAIDs, or both combined are administered, the authors performed a systematic review of related articles and a meta-analysis of data in those articles, which were identified by searching the literature published between 1999 and 2012 using PubMed, Scirus, and Google Scholar. The odds ratios were calculated using the Mantel-Haenszel method. The integrated odds ratios for SSRIs only, NSAIDs only, and the combination were 1.73 (0.65-2.82), 2.55 (1.51-3.59), and 4.02 (2.89-5.15), respectively. Use of the combination resulted in an odds ratio 2.32 times higher than use of either alone. Since the combination of SSRIs and NSAIDs resulted in a significantly higher risk of UGIH than either type of drug alone, clinicians should avoid use of the combination as much as possible. If it is necessary to administer both kinds of drugs, the minimum dosage should be prescribed for the shortest time period possible, and patients, particularly elderly patients, should be closely monitored for development of UGIH and other complications.Key words meta-analyses; epidemiology; combination use; non-steroidal anti-inflammatory drug (NSAID); selective serotonin reuptake inhibitor (SSRI); upper gastrointestinal hemorrhage (UGIH) Selective serotonin reuptake inhibitors (SSRIs) are widely used in the treatment of panic and obsessive compulsive disorders in many countries, and the effects have been confirmed. Usage of SSRIs is increasing because of their low toxicity compared with classical antidepressants, which have a different mode of action.1) Thus, among the many kinds of antidepressants available, SSRIs are currently the most commonly prescribed, and their usage has steadily increased in elderly patients with depression in particular.2) However, SSRIs are reported to have some specific adverse reactions, such as upper gastrointestinal hemorrhage (UGIH). 3)Non-steroidal anti-inflammatory drugs (NSAIDs), which are widely used over-the-counter drugs, have also been shown to be associated with a risk of UGIH.1) Although SSRIs and NSAIDs are sometimes administered in combination, 4) the harmful effects of this combination have not been clarified, as the Food and Drug Administration (FDA) has not accurately analyzed the risk of UGIH resulting from combination use of SSRIs and NSAIDs. 3)Therefore, we collected data for cases of UGIH resulting from the administration of SSRIs alone, NSAIDs alone, and combination use reported between 1999 and 2012, and performed a meta-analysis in order to analyze the risk of UGIH associated with combination use of SSRIs and NSAIDs. METHODS Literature SearchWe searched the literature through PubMed, Scirus, and Google Scholar for articles published between 1999 and 2012 using the following terms: "NSAIDs other drug interaction," "adverse intera...

Prescription drugs associated with false-positive results when using faecal immunochemical tests for colorectal cancer screening

“…We wanted to gather information regarding prescription drug use because our initial hypothesis was that SSRI use, due to its effect on platelet aggregation [12], could explain the difference between the sexes because they are prescribed more often to women. Also, there is evidence that SSRIs may be associated with upper gastrointestinal bleeding, especially when used concurrently with NSAIDs, APAs or OACs [33][34][35]. Although we found the expected association between SSRIs and women (crude OR, 2.8; 95%CI, 1.5-5.2), their use was not shown to be associated with FP results, even when there was concurrent use of these other drugs.…”

Contribution of Helicobacter pylori infection to the risk of peptic ulcer bleeding in patients on nonsteroidal anti‐inflammatory drugs, antiplatelet agents, anticoagulants, corticosteroids and selective serotonin reuptake inhibitors

“…Selective serotonin reuptake inhibitor intake has been associated with a modest increase in the risk of gastroduodenal bleeding (OR = 1.7, 95% CI = 1.4‐1.9) and the risk further increased for patients on joint NSAID therapy (OR = 4.02; 95% CI = 2.89‐5.15) . In our study population, H. pylori infection did not increase the risk of peptic ulcer bleeding in patients on selective serotonin reuptake inhibitor therapy.…”

Effective and safe proton pump inhibitor therapy in acid-related diseases – A position paper addressing benefits and potential harms of acid suppression

“…While the role of steroids, antiplatelet drugs, and anticoagulants is long known, the synergistic effect of selective serotonin reuptake inhibitors (SSRIs) has until recently been overlooked. Over the past 15 years, several epidemiologic studies, summarized by three recent meta-analyses [226–228], have shown an association between SSRI use and the occurrence of UGIB, and found that this risk is further increased among patients, who concomitantly use NSAIDs [229, 230] and/or hold H. pylori infection [231], while it is lowered by concomitant PPI intake [227, 232]. The most plausible mechanisms underlying this detrimental effect include a marked decrease in serotonin platelet content, with consequent impairment of platelet aggregation in response to injury and prolongation of bleeding time as well as an increase in gastric acid secretion, with potential ulcerogenic activity [233, 234].…”

“…When given with NSAIDs, SSRIs may inhibit their metabolism, raising their blood levels and – through impairment of the hemostasis – may promote more severe bleeding. Since the concomitant use of both these drugs results in a significantly higher risk of UGIB than either drug alone [229, 230], this combination should be avoided whenever possible and, if unavoidable, adequate gastroprotection should be adopted from the very beginning [235]. …”