title: Comparison of the effects of serotonin-norepinephrine reuptake inhibitors versus selective serotonin reuptake inhibitors on cerebrovascular events.
abstract: BACKGROUND
  Use of selective serotonin reuptake inhibitors (SSRIs) has been associated with an increased risk of intracranial hemorrhage. However, little is known about cerebrovascular risk in users of serotonin-norepinephrine reuptake inhibitors (SNRIs). Our aim was to determine the differential risk of cerebrovascular events between SSRIs and SNRIs.
  
  
  METHODS
  A nationwide population-based cohort study was conducted in adult patients who started taking SSRIs or SNRIs during the time period 2005 through 2009. The outcome of interest was defined by the first hospitalization diagnosis for ischemic stroke (ICD-9-CM codes 433, 434, 436) or intracranial hemorrhage (ICD-9-CM codes 430, 431, 432). We used a Cox regression model with time-varying medication use and adjusted for stroke risk factors to estimate the hazard ratios (HRs) of ischemic stroke and intracranial hemorrhage associated with SNRI use, using SSRI use as a reference.
  
  
  RESULTS
  Among 582,650 SSRI and 76,920 SNRI initiators with an average follow-up period of 3.2 years, there was a nonsignificantly increased trend toward intracranial hemorrhage (adjusted HR = 1.24 [95% CI, 0.97-1.58]) in SNRI users compared to SSRI users. The risk of ischemic stroke was comparable between the 2 treatment groups (adjusted HR = 1.01 [0.90-1.12]). Similar results were obtained in sensitivity analyses, considering a dose-response relation, allowance of a 7-day grace period between study drug discontinuation and outcome occurrence, and restriction to exclusive users, who remained on the initial treatment. In the subgroup analysis, there was an increased incidence of intracranial hemorrhages in SNRI users compared to SSRI users in patients without prior depression (adjusted HR = 1.63 [1.14-2.32]).
  
  
  CONCLUSIONS
  Use of SNRIs is not associated with an increased risk of either ischemic stroke or intracranial hemorrhage as compared to use of SSRIs in adult patients with depression or anxiety. However, SNRIs should be used cautiously in patients without depression.
authors: Department of Family Medicine, Cathay General Hospital, Taipei, Taiwan.
authors: Yen-Chieh
authors: YC
authors: Lee
authors: Chin-Hsien
authors: CH
authors: Lin
authors: Min-Shung
authors: MS
authors: Lin
authors: Yun
authors: Y
authors: Lu
authors: Chia-Hsuin
authors: CH
authors: Chang
authors: Jou-Wei
authors: JW
authors: Lin
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced* / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000009:adverse effects*; D020521:Stroke / Q000139:chemically induced* / Q000453:epidemiology*; D013624:Taiwan / Q000453:epidemiology
chemical_list: D017367:Selective Serotonin Reuptake Inhibitors; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors