title: Antidepressant Use Is Associated With an Increased Risk of Developing Microbleeds.
abstract: OBJECTIVE
  Serotonin-specific antidepressants may increase the risk of adverse bleeding events. In a previous cross-sectional study, we did not observe an association between antidepressant use and presence of subclinical cerebral bleedings. In this study, we investigated longitudinally whether antidepressant use is associated with an increased risk of new subclinical cerebral microbleeds.
  
  
  METHODS
  In total, 2559 participants aged ≥45 years of the population-based Rotterdam Study, all without microbleeds at baseline, underwent baseline and repeat brain magnetic resonance imaging between 2005 and 2013 (mean time interval, 3.9 years; SD, 0.5) to determine the incidence of microbleeds. Antidepressant use (yes versus no) was assessed between baseline and follow-up scan. In additional analyses, antidepressants were classified as low, intermediate, or high affinity for the serotonin transporter, and alternatively as selective serotonin reuptake inhibitors or non-selective serotonin reuptake inhibitors. We used multivariable logistic regression models to investigate the association of antidepressants with incident microbleeds.
  
  
  RESULTS
  Antidepressant use was associated with a higher cerebral microbleed incidence (odds ratio, 2.22; 95% confidence interval, 1.31-3.76) than nonuse. When stratified by affinity for the serotonin transporter, intermediate serotonin affinity antidepressant use was associated with an increased risk of developing microbleeds (odds ratio, 3.07; 95% confidence interval, 1.53-6.17). Finally, selective serotonin reuptake inhibitor and non-selective serotonin reuptake inhibitor use were both associated with increased microbleed incidence.
  
  
  CONCLUSIONS
  Antidepressant use was associated with an increased risk of developing microbleeds. Our results may support findings from previous clinical studies about increased intracranial and extracranial bleeding risk in antidepressant users.
authors.affiliation: From the Departments of Epidemiology (S.A., N.A., R.N., M.A.I., H.T., A.H., B.H.S., M.W.V., L.E.V.), Radiology (S.A., M. A.I., M.W.V.), Neurology (S.A., M.A.I.), Internal Medicine (N.A., R.N., B.H.S., L.E.V.), Psychiatry (H.T.), and Department of Child and Adolescent Psychiatry (H.T.), Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Inspectorate of Health Care, Utrecht, The Netherlands (B.H.S.); and Apotheek Haagse Ziekenhuizen - HAGA, the Hague, The Netherlands (L.E.V.).
authors.forename: Saloua
authors.initials: S
authors.lastname: Akoudad
authors.affiliation: From the Departments of Epidemiology (S.A., N.A., R.N., M.A.I., H.T., A.H., B.H.S., M.W.V., L.E.V.), Radiology (S.A., M. A.I., M.W.V.), Neurology (S.A., M.A.I.), Internal Medicine (N.A., R.N., B.H.S., L.E.V.), Psychiatry (H.T.), and Department of Child and Adolescent Psychiatry (H.T.), Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Inspectorate of Health Care, Utrecht, The Netherlands (B.H.S.); and Apotheek Haagse Ziekenhuizen - HAGA, the Hague, The Netherlands (L.E.V.).
authors.forename: Nikkie
authors.initials: N
authors.lastname: Aarts
authors.affiliation: From the Departments of Epidemiology (S.A., N.A., R.N., M.A.I., H.T., A.H., B.H.S., M.W.V., L.E.V.), Radiology (S.A., M. A.I., M.W.V.), Neurology (S.A., M.A.I.), Internal Medicine (N.A., R.N., B.H.S., L.E.V.), Psychiatry (H.T.), and Department of Child and Adolescent Psychiatry (H.T.), Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Inspectorate of Health Care, Utrecht, The Netherlands (B.H.S.); and Apotheek Haagse Ziekenhuizen - HAGA, the Hague, The Netherlands (L.E.V.).
authors.forename: Raymond
authors.initials: R
authors.lastname: Noordam
authors.affiliation: From the Departments of Epidemiology (S.A., N.A., R.N., M.A.I., H.T., A.H., B.H.S., M.W.V., L.E.V.), Radiology (S.A., M. A.I., M.W.V.), Neurology (S.A., M.A.I.), Internal Medicine (N.A., R.N., B.H.S., L.E.V.), Psychiatry (H.T.), and Department of Child and Adolescent Psychiatry (H.T.), Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Inspectorate of Health Care, Utrecht, The Netherlands (B.H.S.); and Apotheek Haagse Ziekenhuizen - HAGA, the Hague, The Netherlands (L.E.V.).
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: From the Departments of Epidemiology (S.A., N.A., R.N., M.A.I., H.T., A.H., B.H.S., M.W.V., L.E.V.), Radiology (S.A., M. A.I., M.W.V.), Neurology (S.A., M.A.I.), Internal Medicine (N.A., R.N., B.H.S., L.E.V.), Psychiatry (H.T.), and Department of Child and Adolescent Psychiatry (H.T.), Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Inspectorate of Health Care, Utrecht, The Netherlands (B.H.S.); and Apotheek Haagse Ziekenhuizen - HAGA, the Hague, The Netherlands (L.E.V.).
authors.forename: Henning
authors.initials: H
authors.lastname: Tiemeier
authors.affiliation: From the Departments of Epidemiology (S.A., N.A., R.N., M.A.I., H.T., A.H., B.H.S., M.W.V., L.E.V.), Radiology (S.A., M. A.I., M.W.V.), Neurology (S.A., M.A.I.), Internal Medicine (N.A., R.N., B.H.S., L.E.V.), Psychiatry (H.T.), and Department of Child and Adolescent Psychiatry (H.T.), Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Inspectorate of Health Care, Utrecht, The Netherlands (B.H.S.); and Apotheek Haagse Ziekenhuizen - HAGA, the Hague, The Netherlands (L.E.V.).
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: From the Departments of Epidemiology (S.A., N.A., R.N., M.A.I., H.T., A.H., B.H.S., M.W.V., L.E.V.), Radiology (S.A., M. A.I., M.W.V.), Neurology (S.A., M.A.I.), Internal Medicine (N.A., R.N., B.H.S., L.E.V.), Psychiatry (H.T.), and Department of Child and Adolescent Psychiatry (H.T.), Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Inspectorate of Health Care, Utrecht, The Netherlands (B.H.S.); and Apotheek Haagse Ziekenhuizen - HAGA, the Hague, The Netherlands (L.E.V.). b.stricker@erasmusmc.nl.
authors.forename: Bruno H
authors.initials: BH
authors.lastname: Stricker
authors.affiliation: From the Departments of Epidemiology (S.A., N.A., R.N., M.A.I., H.T., A.H., B.H.S., M.W.V., L.E.V.), Radiology (S.A., M. A.I., M.W.V.), Neurology (S.A., M.A.I.), Internal Medicine (N.A., R.N., B.H.S., L.E.V.), Psychiatry (H.T.), and Department of Child and Adolescent Psychiatry (H.T.), Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Inspectorate of Health Care, Utrecht, The Netherlands (B.H.S.); and Apotheek Haagse Ziekenhuizen - HAGA, the Hague, The Netherlands (L.E.V.).
authors.forename: Meike W
authors.initials: MW
authors.lastname: Vernooij
authors.affiliation: From the Departments of Epidemiology (S.A., N.A., R.N., M.A.I., H.T., A.H., B.H.S., M.W.V., L.E.V.), Radiology (S.A., M. A.I., M.W.V.), Neurology (S.A., M.A.I.), Internal Medicine (N.A., R.N., B.H.S., L.E.V.), Psychiatry (H.T.), and Department of Child and Adolescent Psychiatry (H.T.), Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Inspectorate of Health Care, Utrecht, The Netherlands (B.H.S.); and Apotheek Haagse Ziekenhuizen - HAGA, the Hague, The Netherlands (L.E.V.).
authors.forename: Loes E
authors.initials: LE
authors.lastname: Visser
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects*; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000175:diagnosis* / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000928:Antidepressive Agents
keywords: antidepressive agents; cerebral microbleeds; cerebral small vessel diseases; epidemiology; magnetic resonance imaging