Esketamine, a form of ketamine, has become a breakthrough treatment in mental health for people with treatment-resistant depression (TRD) and major depressive disorder (MDD) with suicidal thoughts. Its fast action means ketamine for depression is especially helpful in emergencies when quick relief is needed.
Esketamine is a slightly different version (or enantiomer) of ketamine, meaning it works more effectively at lower doses. This allows for a stronger antidepressant effect with less risk of misuse. Approved by the U.S. Food and Drug Administration (FDA) in 2019 under the brand name Spravato, esketamine is given as a nasal spray under medical supervision.
How ketamine therapy works and why it’s different
Unlike traditional antidepressants such as SSRIs and SNRIs, which can take weeks to show results, esketamine works within hours by acting on NMDA receptors and influencing glutamate, a key brain chemical. It also boosts brain-derived neurotrophic factor (BDNF), which helps brain cells grow and adapt. This makes esketamine particularly helpful for people who haven’t responded well to other treatments or who need fast relief from suicidal thoughts. In some cases, it allows patients to avoid hospital admission by improving symptoms quickly—sometimes within just a few hours.
Supervised treatment and safety measures
Esketamine must be used under close medical supervision because it can cause temporary side effects. These may include dissociation (feeling disconnected from reality), lightheadedness, drowsiness, nausea, and brief spikes in blood pressure. Some patients may also notice changes in how they perceive colors, sounds, or lights. To manage these effects, clinics like Valens provide quiet, comfortable rooms with monitoring equipment.
After each treatment, patients need to stay at the clinic for about two hours to ensure they recover safely. Driving is not recommended until the following day. Additional guidelines include avoiding other nasal sprays and keeping nasal passages clear before treatment, as well as skipping food and caffeine for a few hours beforehand to enhance the drug’s effects and minimize side effects.
Combining ketamine therapy with other treatments
Although esketamine can relieve depression on its own, the dissociation it causes may also create a window for more effective therapy. This can enhance outcomes when guided psychotherapy is provided during or soon after treatment, though this should only be done by trained professionals. Unlike psychedelics, esketamine’s dissociation is usually mild and short-lived.
Esketamine is typically used along with other medications. The treatment plan often begins with two sessions per week for the first month, followed by once-a-week sessions. The frequency and dosage are adjusted based on how well the patient responds. The goal is to provide lasting relief while fine-tuning other medications as needed.
In emergency situations, esketamine’s fast-acting effects can improve symptoms even during a single session. However, maintaining those improvements requires ongoing treatment and a long-term plan to prevent relapse.
Esketamine offers new hope for people struggling with severe depression and suicidal thoughts. Its rapid action sets it apart from traditional antidepressants, making it a powerful tool for those who need immediate relief. With proper supervision and, when appropriate, combined with therapy, esketamine provides a path toward lasting improvement and a better quality of life.