Analysis of Selective Serotonin Reuptake Inhibitors Associated with QT Prolongation and Torsade de Pointes Adverse Events Based on Data Mining Methods / 中国药学杂志

ABSTRACT

OBJECTIVE: To excavate and evaluate the risk signals of QT prolongation and torsade de pointes(TdP) induced by selective serotonin reuptake inhibitors(SSRIs), provide references for clinical use. METHODS: Data from FDA adverse event reporting system (FAERS, from January 2004 through June 2018) were analyzed for each SSRIs, including fluoxetine, sertraline, citalopram, escitalopram, paroxetine, and fluvoxamine. When QT prolongation and TdP cases were identified using preferred terms (PT) and standardised MedDRA queries (SMQ), three different data mining algorithms were used to detect signalsreporting odds ratio (ROR), medicines and healthcare products regulatory agency (MHRA), and bayesian confidence popagation neural network (BCPNN), if all the three algorithms were positive, suggesting the generation of signals. RESULTS: A total of 3 912 reports of QT prolongation and TdP associated with SSRIs were retrieved through the SMQ. Among which, more females than males(2 349 vs. 1 150), mainly aged 18-44 and 45-64 years, and 90.64% were serious adverse events. The signals were found for fluoxetine, sertraline, citalopram, escitalopram, paroxetine and fluvoxamine at the SMQ level, the RORs (95%CI) were 5.25(4.79-5.76), 2.08(1.79-2.27), 2.86(6.32-7.44), 3.41(3.03-3.84), 2.09(1.84-2.37) and 10.44(8.17-13.33) respectively; the PRRs (X2) were 5.20(1 494.43), 2.01(140.41), 6.77(2 911.71), 3.93(462.34), 2.09(136.58) and 10.21(538.26) respectively; the Ics (IC-2SD) were 2.15(2.12), 1.54(1.52), 2.67(2.65), 2.34(2.31) 1.14(1.12) and 3.16(3.10) respectively. Analysis of the PT included in the SMQ for TdP/QT prolongation, except paroxetine was only detected electrocardiogram QT prolonged signal, all the other SSRIs were detected electrocardiogram QT prolonged and TdP signals. CONCLUSION: QT prolongation may be a SSRIs class effect, but TdP just for fluoxetine, sertraline, citalopram, escitalopram and fluvoxamine. Clinical staff should pay more attention to the differences in adverse drug reaction related to SSRIs, and take pertinence measure to prevent.