Major depressive disorder affects millions worldwide and current antidepressants often don’t work well or take weeks to be effective. Researchers have developed exciting new treatments that work through different brain mechanisms and show promise for rapid symptom relief. These include nasal spray ketamine (approved 2019), oral medications like zuranolone (approved 2023), and investigational treatments including psilocybin, which show benefits especially for treatment-resistant cases. While many show great promise, more research is needed on long-term safety and how to make them widely available.