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A comparative study of QT prolongation with serotonin reuptake inhibitors

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Abstract

Background

QT interval prolongations were described with citalopram and escitalopram. However, the effects of the other serotonin reuptake inhibitors (SRIs) remained discussed. In order to identify a putative signal with other SRIs, the present study investigates the reports of QT interval prolongation with SRIs in two pharmacovigilance databases (PVDB).

Methods

Two kinds of investigations were performed: (1) a comparative study in VigiBase®, the WHO PVDB, where notifications of QT prolongation with six SRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) were selected. Cases with overdose or pregnancy were excluded. The relationship between the “suspected” SRI and occurrence of QT prolongation was assessed by calculating reporting odds ratio (ROR) in a case/non-case design. (2) A descriptive study of QT prolongation reports with citalopram and escitalopram in the French FPVD.

Results

In VigiBase®, 855 notifications were identified (mean age 56.2 years, mainly women 73%). Among them, 172 (20.1%) were associated to escitalopram; 299 (35.0%), to citalopram; 186 (21.8%), to fluoxetine; 94 (11.0%), to sertraline; 66 (7.7%), to paroxetine; and 38 (4.4%) to fluvoxamine. A significant ROR value (higher than 1) was only found for citalopram (3.35 CI95% [2.90–3.87]) or escitalopram (2.50 [2.11–2.95]). In the FPVD, eight reports of QT prolongation were found with citalopram and 27 with escitalopram, mainly in women (77.1%) with a mean age of 73.2 years. In 23 cases (66%), SRIs were associated with other suspected drugs, mainly cardiotropic or psychotropic ones. Hypokalemia was associated in six patients.

Conclusion

This study, performed in real conditions of life, shows a clear signal of QT prolongation with only two SRIs, citalopram and escitalopram, indicating that QT prolongation is not a SRI class effect.

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Acknowledgements

The authors would like to acknowledge the Uppsala Monitoring Center (UMC) which provided and gave permission to use the data analyzed in the present study. The authors also thank the French Network of Pharmacovigilance Centers that contributed to the data. They also wish to thank the French Drug Agency (Agence Nationale de Sécurité du Médicament, ANSM) for the use of the French Pharmacovigilance Database. The content of this article only involved its authors, and the opinions and conclusions are not necessary those of WHO, UMC, or ANSM. Authors of this article are solely responsible for the conclusions.

Contributors

Ana Ojero-Senard, Justine Benevent, Mélanie Araujo, François Montastruc, and Jean-Louis Montastruc designed the study and analyzed the data. Leila Chebane and Melanie Araujo extracted the data, performed the analysis, and prepared the results. Ana Ojero-Senard and Jean-Louis Montastruc wrote the manuscript. All the other authors corrected and approved the manuscript.

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Authors and Affiliations

  1. Laboratoire de Pharmacologie Médicale et Clinique, Centre Midi-Pyrénées de PharmacoVigilance, de Pharmacoépidémiologie et d’Informations sur le Médicament, Pharmacopôle Midi-Pyrénées, INSERM UMR 1027, CIC INSERM 1436, CHU et Faculté de Médecine de Toulouse, Toulouse, France

    Ana Ojero-Senard, Justine Benevent, Emmanuelle Bondon-Guitton, Geneviève Durrieu, Leila Chebane, Melanie Araujo, Francois Montastruc & Jean-Louis Montastruc

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  1. Ana Ojero-Senard
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  2. Justine Benevent
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  3. Emmanuelle Bondon-Guitton
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  4. Geneviève Durrieu
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  5. Leila Chebane
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  6. Melanie Araujo
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  7. Francois Montastruc
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  8. Jean-Louis Montastruc
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Corresponding author

Correspondence to Jean-Louis Montastruc.

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The work was performed during the university research time of the authors using the databases which are available without fees in the department of the authors.

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Ojero-Senard, A., Benevent, J., Bondon-Guitton, E. et al. A comparative study of QT prolongation with serotonin reuptake inhibitors. Psychopharmacology 234, 3075–3081 (2017). https://doi.org/10.1007/s00213-017-4685-7

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