Antipsychotics and risk of QT prolongation: a pharmacovigilance study.
Level 4 - case-series / case-control
Pharmacovigilance disproportionality analysis based on spontaneous adverse event reporting data
PubMed 36515735 · doi:10.1007/s00213-022-06293-4
What was done
Disproportionality analysis using spontaneous adverse event reports recorded from 1967 to 2019 in VigiBase (the World Health Organization's Global Individual Case Safety Reports database) to evaluate the relative risk of reported QT prolongation across 20 different antipsychotic medications. The correlation between reporting risk and drug affinity for the hERG potassium channel was also evaluated.
What was found
Sertindole showed the highest risk of reporting QT prolongation, followed by ziprasidone and amisulpride, while lurasidone showed the lowest risk. First-generation antipsychotics were associated with a higher reporting odds ratio for QT prolongation compared with second-generation antipsychotics (ROR 1.21; 95% CI, 1.10-1.33). The correlation between reporting risk and hERG channel affinity was positive but not statistically significant (R² = 0.14, Pearson r = 0.41, p = 0.1945). Individual ROR values for specific drugs were not provided in the abstract.
Why it matters
These findings provide real-world pharmacovigilance data supporting clinical trial meta-analyses, identifying sertindole and ziprasidone as having the highest reporting risks and lurasidone the lowest reporting risk for QT prolongation.
Limits
The abstract does not disclose the total number of reports analyzed (n). Spontaneous adverse event reporting systems suffer from underreporting, reporting bias, confounding by co-medications or underlying cardiac risk factors, and lack total exposure denominators required to determine true incidence.
Cited by
- supports Geodon (ziprasidone) causes a significant degree of QT interval prolongation.