Use of selective serotonin re-uptake inhibitors and the heart rate corrected QT interval in a real-life setting: the population-based Rotterdam Study

Br J Clin Pharmacol. 2015 Oct;80(4):698-705. doi: 10.1111/bcp.12681. Epub 2015 Jul 29.

Abstract

Aims: 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.

Keywords: electrocardiography; population surveillance; serotonin re-uptake inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Citalopram / adverse effects*
  • Cross-Sectional Studies
  • Databases, Factual
  • Drug Utilization
  • Electrocardiography / drug effects
  • Female
  • Health Surveys
  • Heart Rate*
  • Humans
  • Long QT Syndrome / chemically induced*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Netherlands
  • Selective Serotonin Reuptake Inhibitors / adverse effects*

Substances

  • Serotonin Uptake Inhibitors
  • Citalopram