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

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.

A Thorough QT Study to Evaluate the Effects of a Supratherapeutic Dose of Sertraline on Cardiac Repolarization in Healthy Subjects

“…A meta‐analysis of study‐level data from those trials reported a mean 3.0‐millisecond (95%CI, 2.95‐3.05) increase in QTc interval for sertraline compared with placebo ( P < .0001) . In a prospective, cross‐sectional population‐based study (n = 42), sertraline was associated with a mean QTcF increase of 1.7 milliseconds (90%CI, −3.4 to 6.9) . At suprathreshold doses, however, sertraline has been associated with QTc prolongation.…”

“…Although not a direct relationship, reduction of delayed rectifier potassium/hERG current is considered a surrogate marker of delayed cardiac repolarization . No significant effect of sertraline on QTc was observed in a population‐based cohort study comparing SSRI‐treated adults with untreated individuals or in either of 2 retrospective analyses of electrocardiogram (ECG) records . Nonetheless, pharmacovigilance assessments indicate that QTc prolongation may occur after ingestion of suprathreshold sertraline doses …”

Anksioznost in koronarna bolezen srca

“…Pri predpisovanju antidepresivov moramo biti pri bolnikih s koronarno boleznijo še toliko bolj pozorni na njihov vpliv na podaljšanje intervala QTc (57). Podaljšanje intervala lahko povzroči prekatno aritmijo in nenadno srčno smrt (57).…”

“…Podaljšanje intervala lahko povzroči prekatno aritmijo in nenadno srčno smrt (57). V večji presečni študiji sta bila samo citalopram in escitalopram povezana s podaljšanjem intervala QTc (58), medtem ko je metaanaliza randomiziranih kliničnih raziskav pokazala, da na podaljšanje dobe QTc vplivajo tudi sertralin, paroksetin in fluvoksamin, a manj kot citalopram in escitalopram (59).…”

“…V večji presečni študiji sta bila samo citalopram in escitalopram povezana s podaljšanjem intervala QTc (58), medtem ko je metaanaliza randomiziranih kliničnih raziskav pokazala, da na podaljšanje dobe QTc vplivajo tudi sertralin, paroksetin in fluvoksamin, a manj kot citalopram in escitalopram (59). Citalopram v odmerku 20 mg ali manj je pri starejših od 60 let povečal interval QTc za 20ms (57). Še vedno pa najbolj vplivajo na podaljšanje intervala QTc triciklični antidepresivi (59).…”