For three decades, every new antidepressant worked the same way. Target serotonin. Target norepinephrine. Wait weeks for results. The FDA broke that pattern with esketamine.
Esketamine is a nasal spray. It targets glutamate directly. Standard antidepressants reach glutamate through a slow, indirect route. Esketamine takes the shortcut. Relief can come in hours instead of weeks.
"Too often patients languish with debilitating symptoms, waiting for treatment to work," says Anthony Charuvastra, M.D., Assistant Professor at NYU Medical Center. "Esketamine offers rapid relief and a chance to transition high-risk patients to comprehensive care."
This drug is not for everyone. The FDA restricted it to patients who failed at least two antidepressants during their current episode. You take it in a doctor's office under supervision. You stay for two hours afterward. You cannot drive for 24 hours.
The side effects are significant. Esketamine carries a black box warning. Common reactions include dissociation, dizziness, nausea, vertigo, anxiety, fatigue, vomiting, increased blood pressure, and feeling drunk. Patients over 65 face higher fall and fracture risk from these effects.
Clinical trials showed no significant improvement for patients over 65 with depression.
The cost is steep: roughly $700 per dose.
Esketamine fills a gap for treatment-resistant depression. For patients who have options, the trade-offs deserve careful consideration.