title: SSRI use and risk of fractures among perimenopausal women without mental disorders.
abstract: BACKGROUND
  Selective serotonin reuptake inhibitors (SSRIs) were recently approved by the FDA to treat vasomotor symptoms associated with menopause. No prior study has directly examined whether fracture risk is increased among perimenopausal women who initiate SSRIs or among a population of women without mental disorders more generally.
  
  
  METHODS
  Female patients without mental illness, aged 40-64 years, who initiated SSRIs were compared with a cohort who initiated H2 antagonists (H2As) or proton-pump inhibitors (PPIs) in 1998-2010, using data from a claims database. Standardised mortality ratio weighting was applied using the propensity score odds of treatment to adapt the distribution of characteristics among patients starting H2A/PPIs to the distribution among SSRI initiators. Poisson regression estimated risk differences and Cox proportional hazards regression the RR of fractures among new users of SSRIs versus H2A/PPIs. Primary analyses allowed for a 6-month lag period (ie, exposure begins 6 months after initiation) to account for a hypothesised delay in the onset of any clinically meaningful effect of SSRIs on bone mineral density.
  
  
  RESULTS
  Fracture rates were higher among the 137,031 SSRI initiators compared with the 236,294 H2A/PPI initiators, with HRs (SSRI vs H2A/PPI) over 1, 2 and 5 years of 1.76 (95% CI 1.33 to 2.32), 1.73 (95% CI 1.33 to 2.24) and 1.67 (95% CI 1.30 to 2.14), respectively.
  
  
  CONCLUSIONS
  SSRIs appear to increase fracture risk among middle-aged women without psychiatric disorders, an effect sustained over time, suggesting that shorter duration of treatment may decrease fracture risk. Future efforts should examine whether this association pertains at lower doses.
authors.affiliation: Department of Epidemiology, Harvard University, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors.forename: Yi-han
authors.initials: YH
authors.lastname: Sheu
authors.affiliation: Department of Social and Behavioral Sciences, Harvard University, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Lanteigne
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Gillings School of Global Public Health, Chapel Hill, North Carolina, USA.
authors.forename: Til
authors.initials: T
authors.lastname: Stürmer
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Gillings School of Global Public Health, Chapel Hill, North Carolina, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Pate
authors.affiliation: Department of Health Policy and Management, Harvard University, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Azrael
authors.affiliation: Department of Epidemiology, Harvard University, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA Department of Health Policy and Management, Harvard University, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA Department of Health Sciences, Northeastern University, Boston, Massachusetts, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Miller
mesh_terms: D000328:Adult; D015519:Bone Density; D015331:Cohort Studies; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology* / Q000209:etiology; D019584:Hot Flashes / Q000188:drug therapy*; D006801:Humans; D001523:Mental Disorders; D008875:Middle Aged; D047648:Perimenopause; D012044:Regression Analysis; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D014481:United States / Q000453:epidemiology
chemical_list: D017367:Selective Serotonin Reuptake Inhibitors