Abstract
BACKGROUND: The United States Food and Drug Administration (FDA) maintains a black-box warning for antidepressants warning of an increased risk of suicidality in children and young adults that is based on proprietary clinical trial data from study sponsors that were submitted for regulatory approval. This article aimed to assess whether the black-box warning for antidepressants is still valid today using recent drug safety data. METHODS: Post-marketing adverse drug event data were obtained from the US FDA's Adverse Event Reporting System (FAERS) for the years 2017 through 2023. Logistic regression analysis was conducted using the case versus non-case methodology and adjusted for gender, age group, drug role (primary drug, secondary drug, interacting drug, and concomitant drug), initial FDA reporting year, reporter country, and a drug*gene*age group interaction. RESULTS: In the multivariate analysis, compared to fluoxetine and patients aged 25 to 64 years, children [adjusted reporting odds ratio (aROR) = 7.38, 95% CI, 6.02-9.05] and young adults (aROR = 3.49, 95% CI, 2.65-4.59) were associated with an increased risk of reporting suicidality, but not for the elderly (aROR = 0.76, 95% CI, 0.53-1.09). Relative to fluoxetine, esketamine was associated with the highest rate of reporting suicidality in children (aROR = 3.20, 95% CI, 2.25-4.54); however, esketamine was associated with a lower risk of reporting suicidality in young adults (aROR = 0.59, 95% CI, 0.41-0.84), but not significantly in the elderly (aROR = 0.77, 95% CI, 0.48-1.23). For country-specific findings, relative to the USA, the Slovak Republic, India, and Canada had the lowest risk of reporting suicidality. For the overall study population, desvenlafaxine (aROR = 0.61, 95% CI, 0.46-0.81) and vilazodone (aROR = 0.56, 95% CI, 0.32-0.99) were the only two antidepressants associated with a reduced risk of reporting suicidality. CONCLUSION: This study shows that with recent antidepressant drug safety data, the US FDA's black-box warning for prescribing antidepressants to children and young adults is valid today in the USA. However, relative to the USA, 15 countries had a significantly lower risk of reporting suicidality, while 16 countries had a higher risk of reporting suicidality from 38 antidepressants and lithium.