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

• Published in: British journal of clinical pharmacology 2015-10, Vol.80 (4), p.698-705
• Main Authors: Maljuric, Nevena M., Noordam, Raymond, Aarts, Nikkie, Niemeijer, Maartje N., Berg, Marten E., Hofman, Albert, Kors, Jan A., Stricker, Bruno H., Visser, Loes E.
• Format: Article
• Language: English
• Subjects: Aged; Citalopram - adverse effects; Cross-Sectional Studies; Databases, Factual; Drug Safety; Drug Utilization; electrocardiography; Electrocardiography - drug effects; Female; Health Surveys; Heart Rate; Humans; Long QT Syndrome - chemically induced; Longitudinal Studies; Male; Middle Aged; Netherlands; population surveillance; serotonin re‐uptake inhibitors; Serotonin Uptake Inhibitors - adverse effects
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/bcp.12681

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 QTcF (QT corrected according to Fridericia) measured during use of individual SSRIs with QTcF 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 QTcF 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 QTcF, even after considering the recommended restrictions. Other SSRIs may not give a clinically relevant QTcF prolongation.