Ketamine is an anesthetic that has been used in operating rooms and emergency departments since the 1970s. Over the past two decades, researchers found that a single low dose, far below the level used for surgery, can lift depressive symptoms within hours in many people who have not responded to standard antidepressants. The effect comes from blocking NMDA receptors and setting off a cascade of glutamate signaling that strengthens connections between brain cells. That mechanism is different from SSRIs, which act on serotonin and take weeks to work.
It helps to know the difference between ketamine and esketamine. Generic ketamine given by intravenous infusion or as a compounded lozenge is used off-label for depression, meaning the FDA has not approved it for that purpose and insurance rarely covers it. Esketamine, sold as Spravato, is one half of the ketamine molecule in a nasal spray that the FDA approved in 2019 for treatment-resistant depression, and most insurance plans cover it when criteria are met. Both can cause dissociation, raised blood pressure and nausea during the session, and both have potential for misuse, which is why they are given in supervised settings. Stedfast Psychiatry offers Spravato rather than IV ketamine, because it is approved, monitored under the REMS program, and typically covered by insurance.