Lack of relationship between plasma levels of escitalopram and QTc-interval length

• Published in: European archives of psychiatry and clinical neuroscience Vol. 267; no. 8; pp. 815 - 822
• Main Authors: Carceller-Sindreu, Mar, de Diego-Adeliño, Javier, Portella, Maria J., Garcia-Moll, Xavier, Figueras, Maria, Fernandez-Vidal, Aina, Queraltó, Josep M., Puigdemont, Dolors, Álvarez, Enric
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2017; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antidepressants; Antipsychotics; Citalopram; Citalopram - adverse effects; Citalopram - blood; Coronary artery disease; Cross-Sectional Studies; Electrocardiography - drug effects; Female; Heart diseases; Humans; Male; Medicine; Medicine & Public Health; Mental Disorders - drug therapy; Middle Aged; Myocardial Contraction - drug effects; Neurosciences; Original Paper; Plasma levels; Psychiatry; Psychotropic drugs; Serotonin Uptake Inhibitors - adverse effects; Serotonin Uptake Inhibitors - blood; Tricyclic antidepressants; Young Adult; Electrocardiography; Long QT syndrome/chemically induced; Adverse effects; Escitalopram; Black box warning
• ISSN: 0940-1334; 1433-8491
• DOI: 10.1007/s00406-016-0758-6

Despite safety concerns raised by the European Medicines Agency (EMA), evidence supporting QT-lengthening effects of escitalopram is far to be conclusive. We aimed to evaluate the relationship between escitalopram plasma levels (Escit-PL) and corrected QT-interval length (QTc-length) in 91 outpatients recruited from a hospital setting. Fifteen patients had an abnormally prolonged QTc-interval, and 3 had QTc-intervals ≥500 ms. No correlation between Escit-PL and QTc-length was found ( r  = 0.08; p  = 0.45). Linear/logistic regression analyses were also conducted taking into account potential confounders such as age, gender, personal history of heart disease, medication load and concomitant use of antipsychotic/tricyclic antidepressants. Escit-PL did not predict either QTc-length or abnormally prolonged QTc-interval. Only antipsychotics/tricyclics use (adjusted β  = 0.26, SE = 9.1; p  = 0.01) was an independent predictor of QTc-length ( R 2  = 0.096, F  = 4.68, df  = 2,88; p  = 0.01). Only antipsychotics/tricyclics use (OR 3.56 [95% CI 1.01–12.52]; p  < 0.05) and medication load (OR 1.32 [95% CI 1.06–1.64]; p  < 0.01) were significantly associated with an increased risk of abnormally prolonged QTc-interval (Omnibus test χ 2  = 9.5, df  = 2; p  < 0.01). Our study did not find a significant relationship between Escit-PL and QTc-length even when recognized modulating factors of the QT-interval were controlled for. Concomitant use of other potentially arrhythmogenic agents may help to explain the apparent link between escitalopram and QT prolongation previously suggested. The advisability of maintaining the EMA warning is once again called into question.