FDA will issue a formal REMS update or Dear Healthcare Provider letter for esketamine (Spravato) citing ED suicidality utilization safety signals by February 2027.

Esketamine (Spravato) is a ketamine-based drug the FDA approved for depression, but doctors are now using it off-label (not as approved) to treat suicidal crises in emergency departments without the careful monitoring the FDA required. The FDA monitors real-world safety and will eventually issue a warning letter or instruction update telling doctors how to use it safely, or warning them not to use it in emergency settings where monitoring isn't possible.

Post-market safety obligations under PDUFA require FDA to respond to emergent real-world utilization data. Published data on off-label esketamine use in ED settings for acute suicidality — outside the controlled REMS monitoring environment — creates a documented safety signal FDA cannot ignore without action. A label update or REMS modification is the minimally sufficient institutional response. This is more specific and falsifiable than a general 'scrutiny' prediction: it requires a named regulatory document.