An Association Between Selective Serotonin Reuptake Inhibitor Use and Serious Upper Gastrointestinal Bleeding

Dall, Michael; Muckadell, Ove B Schaffalitzky de; Lassen, Annmarie Touborg; Hansen, Jane Møller; Hallas, Jesper

doi:10.1016/j.cgh.2009.08.019

Cited by 96 publications

(112 citation statements)

References 37 publications

Supporting

Mentioning

104

Contrasting

Unclassified

Order By: Relevance

“…Among these six reports, 2,3,[8][9][10][11] one was a study on the drug interaction between SSRI and NSAIDs, 9) and four also included the interactions of non-SSRIs (serotonin noradrenaline receptor inhibitors; SNRIs) or tricyclic antidepressants (TCAs). 2,8,10,11) The remaining study was a meta-analysis on the interaction between SSRIs and NSAIDs.…”

Section: Data Searchmentioning

confidence: 99%

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

Oka

Okamoto

Kawashita

et al. 2014

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

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...

show abstract

Section: Data Searchmentioning

confidence: 99%

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

Oka

Okamoto

Kawashita

et al. 2014

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…[1][2][3][4] The bleeding risk increases further when SSRIs/SNRIs are used concomitantly with NSAIDs, anticoagulants, and antiplatelet agents. 1,[5][6][7][8] Potential mechanisms that underlie the bleeding risk associated with medications that affect the serotonergic system may include inhibition of serotonin uptake by platelets, SRI-induced increases in gastric acid secretion, and modulation of the CYP450 metabolism. 9,10,26 Certain SSRIs and SNRIs with high protein binding (eg, fluoxetine, duloxetine), when coadministered with another highly bound drug (eg, warfarin), may also increase the free plasma drug concentrations via displacement of proteinbound drug, potentially increasing the risk of adverse events.…”

Section: Discussionmentioning

confidence: 99%

“…The study also evaluated the effects of vortioxetine coadministration on the pharmacokinetics of aspirin and vice versa. In period 1, 28 subjects were randomized to 1 of the 2 sequences in which vortioxetine 10 mg or matching placebo was administered once daily in the morning for 14 days (days [1][2][3][4][5][6][7][8][9][10][11][12][13][14], followed by coadministration with aspirin 150 mg once daily for 6 days (days [15][16][17][18][19][20]. Following a 21-day washout, in period 2, subjects received the alternative treatment.…”

Section: Designmentioning

confidence: 99%

“…[1][2][3][4] This bleeding risk increases further with concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs), anticoagulants, and antiplatelet agents. 1,[5][6][7][8] This effect is thought to be related to platelet serotonin depletion. …”

mentioning

confidence: 99%

“…25 SSRIs and SNRIs are reported to potentially increase the risk of bleeding events, and concomitant use of aspirin, NSAIDs, warfarin, and other anticoagulants with these drugs may potentiate this risk. [1][2][3][4][5][6][7][8] The objectives of the current studies were to evaluate the effects of multiple vortioxetine doses on the pharmacokinetics and pharmacodynamics of aspirin/salicylic acid and the (R)-and (S)-warfarin enantiomers.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Lack of effect of multiple doses of vortioxetine on the pharmacokinetics and pharmacodynamics of aspirin and warfarin

Chen

Zhang

Serenko

2015

The Journal of Clinical Pharmacology

View full text Add to dashboard Cite

Vortioxetine is an antidepressant with multimodal activity approved for the treatment of major depressive disorder. Two separate randomized, placebo-controlled trials evaluated the effects of multiple doses of vortioxetine (10 mg/day) on the pharmacokinetics and pharmacodynamics of aspirin and warfarin in healthy volunteers. In the aspirin study, subjects received vortioxetine 10 mg or placebo once daily for 14 days, followed by coadministration with aspirin 150 mg once daily for 6 days, in 2 periods with a crossover design. In the warfarin study, subjects were randomized after reaching target international normalized ratio (INR) values on warfarin to receive vortioxetine 10 mg or matching placebo once daily for 14 days, with all subjects receiving a maintenance dose of warfarin (1-10 mg). Vortioxetine had no effect on the steady-state pharmacokinetic parameters of aspirin or its metabolite salicylic acid, and no statistically significant effect on the inhibition of arachidonic acid-, adenosine-5 0 -diphosphate-, or collageninduced platelet aggregation at any time points. Coadministration of vortioxetine did not alter the pharmacokinetics of (R)-and (S)-warfarin enantiomers, or the mean coagulation parameters of warfarin treatment alone. Coadministration of vortioxetine doses in healthy volunteers had no effect on aspirin or warfarin pharmacokinetics or pharmacodynamics. Vortioxetine was well tolerated when coadministered with aspirin or warfarin. Keywords vortioxetine, platelet, bleeding, coagulation, pharmacokinetics, drug-drug interactionVarious case reports and epidemiologic studies indicate that selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) may be associated with an increased risk of bleeding. [1][2][3][4] This bleeding risk increases further with concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs), anticoagulants, and antiplatelet agents. 1,[5][6][7][8] This effect is thought to be related to platelet serotonin depletion. 9Based on the observation that serotonin reuptake inhibitor (SRI)-related bleedings most commonly occur in upper gastrointestinal sites, increased gastric acidity associated with some SRIs could be another important mechanism of drug-drug interaction.10 Because warfarin is highly protein-bound, coadministration with other SSRIs or SNRIs with high protein binding, such as fluoxetine and duloxetine, may result in increased levels of free drug, which could contribute to bleeding-related complications. 11Vortioxetine was approved by FDA and European Union (EU) in 2013 for the treatment of major depressive disorder (MDD). 12,13 The pharmacokinetic profile of vortioxetine is linear and dose-proportional with moderate oral bioavailability, extensive tissue distribution, and a long elimination half-life.14 Vortioxetine is extensively metabolized primarily through oxidation via multiple CYP450 isozymes and subsequent glucuronic acid conjugation. CYP2D6 is the primary enzyme catalyzing the metabolism of vortioxetine...

show abstract

Antidepressants and Bleeding Risk After Face-lift Surgery

Harirchian

Zoumalan

Rosenberg

2012

Archives of Facial Plastic Surgery

View full text Add to dashboard Cite

An Association Between Selective Serotonin Reuptake Inhibitor Use and Serious Upper Gastrointestinal Bleeding

Cited by 96 publications

References 37 publications

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

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

Lack of effect of multiple doses of vortioxetine on the pharmacokinetics and pharmacodynamics of aspirin and warfarin

Antidepressants and Bleeding Risk After Face-lift Surgery

Contact Info

Product

Resources

About