title: Use of selective serotonin re-uptake inhibitors and the heart rate corrected QT interval in a real-life setting: the population-based Rotterdam Study.
abstract: OBJECTIVE
  Selective serotonin re-uptake inhibitors (SSRIs), specifically citalopram and escitalopram, are thought to cause QTc prolongation, although studies have shown contradictory results. Nevertheless, a maximum citalopram dosage of 20 mg in high risk patients (e.g. >60 years of age) is recommended. We aimed to investigate the association between use of (individual) SSRIs and QTc in a population-based study in older adults.
  
  
  METHODS
  This study, which was part of the prospective Rotterdam Study (period 1991-2012), included participants with up to five electrocardiograms (ECGs). We used linear mixed models to compare QTc F (QT corrected according to Fridericia) measured during use of individual SSRIs with QTc F measured during non-use of any antidepressant. For citalopram, analyses were additionally restricted to a maximum dosage of 20 mg in participants aged 60 years and older.
  
  
  RESULTS
  We included 12 589 participants with a total of 26 620 ECGs of which 436 ECGs were made during SSRI use. The mean QTc F was similar during use of any drugs from the SSRI class and during non-use. After stratifying to individual SSRIs, ECGs recorded during use of citalopram had the longest QTc compared with ECGs recorded during non-use (+12.8 ms, 90% CI 7.5, 18.2). This result remained similar in the analysis comprising participants aged 60 years and older with a maximum prescribed daily dosage of 20 mg citalopram.
  
  
  CONCLUSIONS
  Although no SSRI class effect was observed, use of citalopram was associated with a longer QTc F, even after considering the recommended restrictions. Other SSRIs may not give a clinically relevant QTc F prolongation.
authors.affiliation: Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam.
authors.forename: Nevena M
authors.initials: NM
authors.lastname: Maljuric
authors.affiliation: Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam.|Department of Internal Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam.
authors.forename: Raymond
authors.initials: R
authors.lastname: Noordam
authors.affiliation: Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam.|Department of Internal Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam.
authors.forename: Nikkie
authors.initials: N
authors.lastname: Aarts
authors.affiliation: Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam.
authors.forename: Maartje N
authors.initials: MN
authors.lastname: Niemeijer
authors.affiliation: Department of Medical Informatics, Erasmus MC - University Medical Center Rotterdam, Rotterdam.
authors.forename: Marten E
authors.initials: ME
authors.lastname: van den Berg
authors.affiliation: Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Medical Informatics, Erasmus MC - University Medical Center Rotterdam, Rotterdam.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Kors
authors.affiliation: Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam.|Department of Internal Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam.|Inspectorate of Health Care, Utrecht.
authors.forename: Bruno H
authors.initials: BH
authors.lastname: Stricker
authors.affiliation: Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam.|Department of Internal Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam.|Apotheek Haagse Ziekenhuizen - HAGA, The Hague, the Netherlands.
authors.forename: Loes E
authors.initials: LE
authors.lastname: Visser
mesh_terms: D000368:Aged; D015283:Citalopram / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D016208:Databases, Factual; D004363:Drug Utilization; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006306:Health Surveys; D006339:Heart Rate; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*
chemical_list: D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors
keywords: electrocardiography; population surveillance; serotonin re-uptake inhibitors