Antipsychotics and risk of QT prolongation: a pharmacovigilance study

• Published in: Psychopharmacology Vol. 240; no. 1; pp. 199 - 202
• Main Authors: Bordet, Constance, Garcia, Philippe, Salvo, Francesco, Touafchia, Anthony, Galinier, Michel, Sommet, Agnès, Montastruc, François
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.01.2023; Springer; Springer Nature B.V; Springer Verlag
• Subjects: Affinity; Amisulpride; Antipsychotic Agents - adverse effects; Antipsychotic drugs; Antipsychotics; Aripiprazole; Biomedical and Life Sciences; Biomedicine; Clinical trials; Complications and side effects; HERG protein; Humans; Life Sciences; Long QT syndrome; Long QT Syndrome - chemically induced; Long QT Syndrome - epidemiology; Lurasidone Hydrochloride - adverse effects; Neurosciences; Original Investigation; Pharmacology/Toxicology; Pharmacovigilance; Potassium channels (voltage-gated); Psychiatry; Psychotropic drugs; Risk factors; Santé publique et épidémiologie; Statistics; Ziprasidone; France; Antipsychotics; hERG; Lurasidone; QT prolongation; Pharmacovigilance
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-022-06293-4

Rationale While meta-analyses of clinical trials found that lurasidone and partial dopamine agonists (brexpiprazole and aripiprazole) were the antipsychotics less likely to cause QTc prolongation, and sertindole, amisulpride, and ziprasidone were the most frequently associated with this adverse drug reaction; no real-world studies have investigated this risk between the different antipsychotics. Objectives and methods Using data recorded from 1967 to 2019 in VigiBase®, the World Health Organization’s Global Individual Case Safety Reports database, we performed disproportionality analysis to investigate the risk of reporting QT prolongation between 20 antipsychotics. Results Sertindole had the highest risk of reporting QT prolongation, followed by ziprasidone and amisulpride. Lurasidone was associated with the lowest risk. First-generation antipsychotics were associated with a greater QT prolongation reporting risk (ROR, 1.21; 95%CI, 1.10–1.33) than second-generation antipsychotics. A positive correlation was found between the risk of reporting QT prolongation and affinity for hERG channel ( R 2  = 0.14, slope = Pearson coefficient = 0.41, p value = 0.1945). Conclusions This large study in a real-world setting suggests that sertindole and ziprasidone were the antipsychotics drugs associated with the highest risk of QT prolongation reporting. Our results suggest that lurasidone is less associated with QT interval prolongation reports. Our study also suggests that antipsychotics with the higher hERG affinity are more associated with to QT prolongations reports.