title: Lack of relationship between plasma levels of escitalopram and QTc-interval length.
abstract: 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 (R2= 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 χ2= 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.
authors.affiliation: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau (IIB-SantPau), Universitat Autònoma de Barcelona (UAB), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), C/ Sant Antoni Maria Claret, 167, 08025, Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Carceller-Sindreu
authors.affiliation: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau (IIB-SantPau), Universitat Autònoma de Barcelona (UAB), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), C/ Sant Antoni Maria Claret, 167, 08025, Barcelona, Spain. fdiego@santpau.cat.
authors.forename: Javier
authors.identifier: http://orcid.org/0000-0001-9708-2441
authors.initials: J
authors.lastname: de Diego-Adeliño
authors.affiliation: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau (IIB-SantPau), Universitat Autònoma de Barcelona (UAB), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), C/ Sant Antoni Maria Claret, 167, 08025, Barcelona, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Portella
authors.affiliation: Department of Cardiology, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau (IIB-SantPau), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Garcia-Moll
authors.affiliation: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau (IIB-SantPau), Universitat Autònoma de Barcelona (UAB), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), C/ Sant Antoni Maria Claret, 167, 08025, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Figueras
authors.affiliation: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau (IIB-SantPau), Universitat Autònoma de Barcelona (UAB), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), C/ Sant Antoni Maria Claret, 167, 08025, Barcelona, Spain.
authors.forename: Aina
authors.initials: A
authors.lastname: Fernandez-Vidal
authors.affiliation: Department of Biochemistry, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Queraltó
authors.affiliation: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau (IIB-SantPau), Universitat Autònoma de Barcelona (UAB), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), C/ Sant Antoni Maria Claret, 167, 08025, Barcelona, Spain.
authors.forename: Dolors
authors.initials: D
authors.lastname: Puigdemont
authors.affiliation: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau (IIB-SantPau), Universitat Autònoma de Barcelona (UAB), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), C/ Sant Antoni Maria Claret, 167, 08025, Barcelona, Spain.
authors.forename: Enric
authors.initials: E
authors.lastname: Álvarez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015283:Citalopram / Q000009:adverse effects* / Q000097:blood*; D003430:Cross-Sectional Studies; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy*; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000097:blood*; D055815:Young Adult
chemical_list: D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Adverse effects; Black box warning; Electrocardiography; Escitalopram; Long QT syndrome/chemically induced