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

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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 (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.

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Acknowledgements

Dr. de Diego-Adeliño is funded by the Instituto de Salud Carlos III through a “Juan Rodés” research fellowship (JR14/00011). Dr. Portella is funded by the Ministerio de Ciencia e Innovación of the Spanish Government and by the Instituto de Salud Carlos III through a “Miguel Servet” research contract (CP10-00393), co-financed by the European Regional Development Fund (ERDF) (2013–2016). The funding agencies mentioned had no role in the design, conduct and publication of the study.

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Authors and Affiliations

  1. 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

    Mar Carceller-Sindreu, Javier de Diego-Adeliño, Maria J. Portella, Maria Figueras, Aina Fernandez-Vidal, Dolors Puigdemont & Enric Álvarez

  2. 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

    Xavier Garcia-Moll

  3. Department of Biochemistry, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain

    Josep M. Queraltó

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  1. Mar Carceller-Sindreu
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Correspondence to Javier de Diego-Adeliño.

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Conflict of interest

Dr. de Diego-Adeliño has received lecture honoraria from Pfizer, GlaxoSmithKline and Lundbeck. Dr. Alvarez has received consulting and lecture honoraria from Eli Lilly, Lundbeck, Pfizer, Sanofi-Aventis and Otsuka; has participated as principal local investigator in clinical trials sponsored by Eli Lilly, Bristol-Myrers Squibb, Sanofi-Aventis and AB·Biotics; and has served as national coordinator of clinical trials sponsored by Servier and Lundbeck. The remaining authors report no financial or other relationship relevant to the subject of this article.

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Carceller-Sindreu, M., de Diego-Adeliño, J., Portella, M.J. et al. Lack of relationship between plasma levels of escitalopram and QTc-interval length. Eur Arch Psychiatry Clin Neurosci 267, 815–822 (2017). https://doi.org/10.1007/s00406-016-0758-6

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