title: Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: cohort study using primary care database.
abstract: OBJECTIVE
  To assess associations between different antidepressant treatments and rates of three cardiovascular outcomes (myocardial infarction, stroke or transient ischaemic attack, and arrhythmia) in people with depression.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  UK general practices contributing to the QResearch primary care database.
  
  
  METHODS
  238,963 patients aged 20 to 64 years with a first diagnosis of depression between 1 January 2000 and 31 July 2011.
  
  
  METHODS
  Antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, duration of use, and commonly prescribed individual antidepressant drugs.
  
  
  METHODS
  First diagnoses of myocardial infarction, stroke or transient ischaemic attack, and arrhythmia during five years' follow-up. Cox proportional hazards models were used to estimate hazard ratios, adjusting for potential confounding variables.
  
  
  RESULTS
  During five years of follow-up, 772 patients had a myocardial infarction, 1106 had a stroke or transient ischaemic attack, and 1452 were diagnosed as having arrhythmia. No significant associations were found between antidepressant class and myocardial infarction over five years' follow-up. In the first year of follow-up, patients treated with selective serotonin reuptake inhibitors had a significantly reduced risk of myocardial infarction (adjusted hazard ratio 0.58, 95% confidence interval 0.42 to 0.79) compared with no use of antidepressants; among individual drugs, fluoxetine was associated with a significantly reduced risk (0.44, 0.27 to 0.72) and lofepramine with a significantly increased risk (3.07, 1.50 to 6.26). No significant associations were found between antidepressant class or individual drugs and risk of stroke or transient ischaemic attack. Antidepressant class was not significantly associated with arrhythmia over five years' follow-up, although the risk was significantly increased during the first 28 days of treatment with tricyclic and related antidepressants (adjusted hazard ratio 1.99, 1.27 to 3.13). Fluoxetine was associated with a significantly reduced risk of arrhythmia (0.74, 0.59 to 0.92) over five years, but citalopram was not significantly associated with risk of arrhythmia even at high doses (1.11, 0.72 to 1.71 for doses ≥ 40 mg/day).
  
  
  CONCLUSIONS
  This study found no evidence that selective serotonin reuptake inhibitors are associated with an increased risk of arrhythmia or stroke/transient ischaemic attack in people diagnosed as having depression between the ages of 20 to 64 or that citalopram is associated with a significantly increased risk of arrhythmia. It found some indication of a reduced risk of myocardial infarction with selective serotonin reuptake inhibitors, particularly fluoxetine, and of an increased risk with lofepramine.
authors.affiliation: Division of Primary Care, School of Medicine, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Carol
authors.initials: C
authors.lastname: Coupland
authors.affiliation: Division of Primary Care, School of Medicine, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Trevor
authors.initials: T
authors.lastname: Hill
authors.affiliation: Institute of Mental Health, Nottingham NG8 1BB, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Morriss
authors.affiliation: University of Southampton Medical School, Primary Care and Population Sciences, Aldermoor Health Centre, Southampton SO16 5ST, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Moore
authors.affiliation: School of Health Sciences, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich NR4 7TJ, UK.
authors.forename: Antony
authors.initials: A
authors.lastname: Arthur
authors.affiliation: Division of Primary Care, School of Medicine, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Hippisley-Cox
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000175:diagnosis; D016208:Databases, Factual; D003863:Depression / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011320:Primary Health Care; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000928:Antidepressive Agents; D017367:Selective Serotonin Reuptake Inhibitors