The FDA gave a special fast-track approval to a nasal spray called esketamine for people with severe depression who might try to kill themselves, not because they’re sure it works, but because they felt it was urgent to try.

A meta-analysis of all completed RCTs comparing intranasal esketamine to placebo or standard care in adults with treatment-resistant depression and imminent suicide risk, measuring clinical improvement and safety outcomes over 4–12 weeks, to determine whether efficacy was established at the time of FDA designation.

A prospective cohort study tracking patients prescribed intranasal esketamine under FDA Breakthrough Therapy guidelines to assess real-world clinical outcomes and safety signals compared to historical controls, to evaluate whether observed benefits justified regulatory urgency.

A case-control analysis comparing FDA decisions on esketamine to other drugs granted Breakthrough Therapy Designation, examining whether urgency was driven by unmet need and preliminary data rather than robust efficacy evidence.

A preclinical study in rodent models of depression and suicidal behavior to assess whether esketamine’s mechanism of action supports rapid antidepressant effects, potentially justifying regulatory urgency.

A qualitative analysis of FDA advisory committee transcripts, internal memos, and public statements to determine whether efficacy data were deemed insufficient and urgency was the primary driver of designation.