Selective serotonin re‐uptake inhibiting antidepressants and the risk of overanticoagulation during acenocoumarol maintenance treatment

Teichert, Martina; Visser, Loes E.; Uitterlinden, André G.; Hofman, Albert; Buhre, Peter J.; Straus, Sabine M. J. M.; Smet, Peter A. G. M. De; Stricker, Bruno H.

doi:10.1111/j.1365-2125.2011.04004.x

“…21-23 A study by Teichert et al showed that users of SSRIs were more likely to be over-anticoagulated, although our analysis found a significant association even after controlling for supratherapeutic INRs. 24 Labos et al reported that patients taking antiplatelet agents had significant increases in bleeding risk among those patients taking aspirin, clopidogrel, or both along with an SSRI when compared to their non-SSRI taking counterparts. 25 Recent evidence has suggested improved physical and psychological outcomes in patients treated with SSRIs after stroke.…”

Section: Discussionmentioning

confidence: 99%

Effect of Selective Serotonin Reuptake Inhibitors on Bleeding Risk in Patients With Atrial Fibrillation Taking Warfarin

Quinn

¹

,

Singer

²

,

Chang

³

et al. 2014

The American Journal of Cardiology

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Selective serotonin reuptake inhibitor (SSRI) medications have been linked to increased bleeding risk, however, the actual association between warfarin, SSRI exposure, and bleeding risk has not been well-established. We studied the AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA) cohort of 13,559 adults with atrial fibrillation (AF), restricted to the 9186 patients contributing follow-up time while taking warfarin. Exposure to SSRIs and tricyclic antideprssants (TCAs) were assessed from pharmacy database dispensing data. The main outcome was hospitalization for major hemorrhage. Results were adjusted for bleeding risk and time in an INR range ≥ 3. We identified 461 major hemorrhages during 32,888 person-years of follow-up, 45 events during SSRI use, 12 during TCA only use, and 404 without either medication. Hemorrhage rates were higher during periods of SSRI exposure compared with periods on no antidepressants (2.32 per 100 person-years vs. 1.35 per 100 person-years, p ≤ 0.001) and did not differ between TCA exposure and no antidepressants (1.30 per 100 person-years on TCAs, p = 0.93). After adjusting for bleeding risk and time in INR range > 3, SSRI exposure was associated with an increased rate of hemorrhage compared with no antidepressants (adjusted relative risk 1.41, 95% CI: 1.04-1.92, p=0.03), whereas TCA exposure was not (adjusted relative risk 0.82, 95% CI: 0.46-1.46, p=0.50). In conclusion, SSRI exposure was associated with higher major hemorrhage risk in patients on warfarin and this risk should be considered when selecting antidepressant treatments in those patients.

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“…The SSRIs are among the most commonly prescribed drug classes . Fluvoxamine and fluoxetine are the two SSRIs most likely to inhibit warfarin metabolism, which is supported by several case reports.…”

Section: Specific Drug‐drug Interactions By Psychotropic Classmentioning

confidence: 82%

Drug‐Drug Interactions Between Warfarin and Psychotropics: Updated Review of the Literature

Nadkarni

¹

,

Oldham

²

,

Howard

³

et al. 2012

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As the number of psychotropics on the market expands, the likelihood increases that a patient requiring anticoagulation with warfarin will receive concurrent treatment with a psychotropic drug. Because warfarin undergoes hepatic metabolism and is highly protein bound, it is particularly prone to drug interactions; in addition, its relatively narrow therapeutic window places patients at risk of either hemorrhagic or thrombotic complications. Although warfarin's interactions with other drugs have long been studied, the most recent review of the literature of warfarin's interactions with psychotropics was over a decade ago. Thus, we conducted a systematic review of the literature documenting the interaction between warfarin and psychotropics, with a focus on interactions mediated through the cytochrome P450 system and protein binding. A search of the MEDLINE database was performed, and reports of warfarin interactions with psychotropics were identified. The results suggest that interactions between warfarin and psychotropic drugs are important and likely underrecognized. They also have notable implications for both safety and drug compliance. When certain psychotropics are started or discontinued in patients receiving warfarin therapy, or when warfarin is introduced to a patient receiving a stable dose of a psychotropic, clinicians should monitor a patient's international normalized ratio (INR) closely to ensure it remains within therapeutic range. Psychotropics that pose a particular risk of increasing the INR when used with warfarin include fluoxetine, fluvoxamine, quetiapine, and valproic acid. Psychotropics that may significantly decrease the INR when used with warfarin include trazodone, St. John's wort, carbamazepine, and the polycyclic aromatic carbons in tobacco cigarettes; however, nicotine itself, as in nicotine replacement strategies, is not known to alter warfarin's anticoagulant effect. In certain cases, the need for anticoagulation may also necessitate switching to a different psychotropic.

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“…The SSRIs are among the most commonly prescribed drug classes. 70 Fluvoxamine 12, 13 and fluoxetine [14][15][16] are the two SSRIs most likely to inhibit warfarin metabolism, which is supported by several case reports. In two reports of a fluvoxamine interaction with warfarin, the INR was elevated without hemorrhagic complications, 12,13 although in one report of a fluoxetine-warfarin interaction, an elderly man experienced a fatal intracerebral hemorrhage.…”

Section: Antidepressantsmentioning

confidence: 83%

Drug-Drug Interactions Between Warfarin and Psychotropics: Updated Review of the Literature

Nadkarni

¹

,

Oldham

²

,

Howard

³

et al. 2012

View full text Add to dashboard Cite

As the number of psychotropics on the market expands, the likelihood increases that a patient requiring anticoagulation with warfarin will receive concurrent treatment with a psychotropic drug. Because warfarin undergoes hepatic metabolism and is highly protein bound, it is particularly prone to drug interactions; in addition, its relatively narrow therapeutic window places patients at risk of either hemorrhagic or thrombotic complications. Although warfarin's interactions with other drugs have long been studied, the most recent review of the literature of warfarin's interactions with psychotropics was over a decade ago. Thus, we conducted a systematic review of the literature documenting the interaction between warfarin and psychotropics, with a focus on interactions mediated through the cytochrome P450 system and protein binding. A search of the MEDLINE database was performed, and reports of warfarin interactions with psychotropics were identified. The results suggest that interactions between warfarin and psychotropic drugs are important and likely underrecognized. They also have notable implications for both safety and drug compliance. When certain psychotropics are started or discontinued in patients receiving warfarin therapy, or when warfarin is introduced to a patient receiving a stable dose of a psychotropic, clinicians should monitor a patient's international normalized ratio (INR) closely to ensure it remains within therapeutic range. Psychotropics that pose a particular risk of increasing the INR when used with warfarin include fluoxetine, fluvoxamine, quetiapine, and valproic acid. Psychotropics that may significantly decrease the INR when used with warfarin include trazodone, St. John's wort, carbamazepine, and the polycyclic aromatic carbons in tobacco cigarettes; however, nicotine itself, as in nicotine replacement strategies, is not known to alter warfarin's anticoagulant effect. In certain cases, the need for anticoagulation may also necessitate switching to a different psychotropic.

show abstract

Selective serotonin re‐uptake inhibiting antidepressants and the risk of overanticoagulation during acenocoumarol maintenance treatment

Cited by 16 publications

References 40 publications

Effect of Selective Serotonin Reuptake Inhibitors on Bleeding Risk in Patients With Atrial Fibrillation Taking Warfarin

Effect of Selective Serotonin Reuptake Inhibitors on Bleeding Risk in Patients With Atrial Fibrillation Taking Warfarin

Drug‐Drug Interactions Between Warfarin and Psychotropics: Updated Review of the Literature

Drug-Drug Interactions Between Warfarin and Psychotropics: Updated Review of the Literature

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