Association between warfarin combined with serotonin-modulating antidepressants and increased case fatality in primary intracerebral hemorrhage: a population-based study.

OBJECTIVE

Patients receiving oral anticoagulants run a higher risk of cerebral hemorrhage with a poor outcome. Serotonin-modulating antidepressants (selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs]) are frequently used in combination with warfarin, but it is unclear whether this combination of drugs influences outcome after primary intracerebral hemorrhage (PICH). The authors investigated case fatality in PICH among patients from a defined population who were receiving warfarin alone, with aspirin, or with serotonin-modulating antidepressants.

METHODS

Nine hundred eighty-two subjects with PICH were derived from the population of Northern Ostrobothnia, Finland, for the years 1993-2008, and those with warfarin-associated PICH were eligible for analysis. Their hospital records were reviewed, and medication data were obtained from the national register of prescribed medicines. Kaplan-Meier survival curves were drawn to illustrate cumulative case fatality, and a Cox proportional-hazards analysis was performed to demonstrate predictors of death.

RESULTS

Of the 176 patients eligible for analysis, 17 had been taking aspirin and 19 had been taking SSRI/SNRI together with warfarin. The 30-day case fatality rates were 50.7%, 58.8%, and 78.9%, respectively, for those taking warfarin alone, with aspirin, or with SSRI/SNRI (p = 0.033, warfarin plus SSRI/SNRI compared with warfarin alone). Warfarin combined with SSRI/SNRI was a significant independent predictor of case fatality (adjusted HR 2.10, 95% CI 1.13-3.92, p = 0.019).

CONCLUSIONS

Concurrent use of warfarin and a serotonin-modulating antidepressant, relative to warfarin alone, seemed to increase the case fatality rate for PICH. This finding should be taken into account if hematoma evacuation is planned.