Ana Ojero-Senard1, Justine Benevent1, Emmanuelle Bondon-Guitton1, Geneviève Durrieu1, Leila Chebane1, Melanie Araujo1, Francois Montastruc1, Jean-Louis Montastruc2. 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. 2. 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. jean-louis.montastruc@univ-tlse3.fr.
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.
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.
Authors: P Weeke; A Jensen; F Folke; G H Gislason; J B Olesen; C Andersson; E L Fosbøl; J K Larsen; F K Lippert; S L Nielsen; T Gerds; P K Andersen; J K Kanters; H E Poulsen; S Pehrson; L Køber; C Torp-Pedersen Journal: Clin Pharmacol Ther Date: 2012-05-16 Impact factor: 6.875
Authors: Cecilia Aström-Lilja; Johanna Mercke Odeberg; Elisabet Ekman; Staffan Hägg Journal: Pharmacoepidemiol Drug Saf Date: 2008-06 Impact factor: 2.890
Authors: Thomas S Rector; Selcuk Adabag; Francesca Cunningham; David Nelson; Eric Dieperink Journal: Am J Psychiatry Date: 2016-05-10 Impact factor: 18.112
Authors: Nevena M Maljuric; Raymond Noordam; Nikkie Aarts; Maartje N Niemeijer; Marten E van den Berg; Albert Hofman; Jan A Kors; Bruno H Stricker; Loes E Visser Journal: Br J Clin Pharmacol Date: 2015-07-29 Impact factor: 4.335
Authors: Charles E Leonard; Warren B Bilker; Craig Newcomb; Stephen E Kimmel; Sean Hennessy Journal: Pharmacoepidemiol Drug Saf Date: 2011-07-28 Impact factor: 2.890
Authors: Victor M Castro; Caitlin C Clements; Shawn N Murphy; Vivian S Gainer; Maurizio Fava; Jeffrey B Weilburg; Jane L Erb; Susanne E Churchill; Isaac S Kohane; Dan V Iosifescu; Jordan W Smoller; Roy H Perlis Journal: BMJ Date: 2013-01-29
Authors: Dustin Latimer; Michael D Stocker; Kia Sayers; Jackson Green; Adam M Kaye; Alaa Abd-Elsayed; Elyse M Cornett; Alan D Kaye; Giustino Varrassi; Omar Viswanath; Ivan Urits Journal: Psychopharmacol Bull Date: 2021-06-01