title: Association between warfarin combined with serotonin-modulating antidepressants and increased case fatality in primary intracerebral hemorrhage: a population-based study.
abstract: 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.
authors: Departments of Neurosurgery.
authors: Pekka
authors: P
authors: Löppönen
authors: Sami
authors: S
authors: Tetri
authors: Seppo
authors: S
authors: Juvela
authors: Juha
authors: J
authors: Huhtakangas
authors: Pertti
authors: P
authors: Saloheimo
authors: Michaela K
authors: MK
authors: Bode
authors: Matti
authors: M
authors: Hillbom
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002543:Cerebral Hemorrhage / Q000453:epidemiology* / Q000401:mortality*; D003863:Depression / Q000188:drug therapy; D004359:Drug Therapy, Combination; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D020521:Stroke / Q000517:prevention & control; D015996:Survival Rate; D016896:Treatment Outcome; D014859:Warfarin / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D000928:Antidepressive Agents; D017367:Selective Serotonin Reuptake Inhibitors; D014859:Warfarin
keywords: GCS = Glasgow Coma Scale; ICH = intracerebral hemorrhage; INR = international normalized ratio; PTCC = prothrombin complex concentrate; SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor; WA-PICH = warfarin-associated primary ICH; case fatality; intracerebral hemorrhage; serotonin-modulating antidepressant; vascular disorders; warfarin