Esketamine is the active ingredient in Spravato, a nasal spray approved by the FDA for treatment-resistant depression. Ketamine is a mixture of two mirror-image molecules, and esketamine is the S-form, which binds more strongly to the NMDA receptor. That receptor normally responds to glutamate, the brain's main excitatory chemical messenger. By briefly blocking it, esketamine triggers a surge of glutamate signaling that appears to prompt the growth of new synaptic connections in regions involved in mood. This mechanism is different from SSRIs and SNRIs, which act on serotonin and norepinephrine, and it may explain why some people who did not respond to those medications improve with esketamine.
The FDA approved esketamine in 2019 for adults with treatment-resistant depression and in 2020 for adults with major depressive disorder who have acute suicidal thoughts or behavior. It is always used together with an oral antidepressant. Because esketamine can cause dissociation, sedation and a temporary rise in blood pressure, it is only given in certified clinics under a safety program called REMS. You self-administer the spray in the office and stay for at least two hours of monitoring. Esketamine is not sent home with patients. Stedfast Psychiatry offers it at our Boynton Beach, Palm Beach Gardens and Royal Palm Beach offices.