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

Br J Clin Pharmacol. 2011 Nov;72(5):798-805. doi: 10.1111/j.1365-2125.2011.04004.x.

Abstract

Aim: The aim of this study was to investigate the effects of co-medication with selective serotonin re-uptake inhibitors (SSRIs) on overanticoagulation during acenocoumarol maintenance treatment.

Methods: All subjects from The Rotterdam Study who received acenocoumarol maintenance treatment between April 1 1991 and September 9 2009 were followed for the event of an international normalized ratio (INR) ≥6, until death, end of treatment or end of the study period. With the Andersen-Gill extension of the Cox proportional hazards model, risks for repeated events of overanticoagulation in relation to concomitant SSRI use were calculated.

Results: The risk for overanticoagulation during acenocoumarol maintenance treatment was increased in combination with fluvoxamine (HR 2.63, 95% CI 1.49, 4.66) and venlafaxine (HR 2.19, 95% CI 1.21, 3.99). There was no increase in risk for the other SSRIs, but numbers of exposed cases were low for all SSRIs except paroxetine.

Conclusion: Fluvoxamine and venlafaxine were associated with a more than double risk of INR values ≥6 in acenocoumarol treated subjects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acenocoumarol / therapeutic use*
  • Aged
  • Aged, 80 and over
  • Anticoagulants / therapeutic use*
  • Antidepressive Agents / pharmacology*
  • Blood Coagulation / drug effects
  • Cohort Studies
  • Cyclohexanols / pharmacology
  • Drug Interactions
  • Fluvoxamine / pharmacology
  • Hemorrhage / chemically induced
  • Humans
  • Middle Aged
  • Proportional Hazards Models
  • Risk Factors
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Serotonin / pharmacology*
  • Venlafaxine Hydrochloride

Substances

  • Anticoagulants
  • Antidepressive Agents
  • Cyclohexanols
  • Serotonin Uptake Inhibitors
  • Serotonin
  • Venlafaxine Hydrochloride
  • Acenocoumarol
  • Fluvoxamine