Spravato Treatment
Spravato® (Esketamine) for Treatment-Resistant Depression
Spravato (esketamine) is an FDA-approved nasal spray medication used, in conjunction with an oral antidepressant, to treat treatment-resistant depression (TRD) in adults. TRD is generally defined as major depressive disorder that has not responded adequately to at least two different antidepressant treatments.
​
How it works:
Esketamine is derived from ketamine and works differently than traditional antidepressants (such as SSRIs or SNRIs), which typically target serotonin or norepinephrine pathways. Esketamine acts on the NMDA receptor, a glutamate receptor pathway, which is thought to contribute to its distinct mechanism of action.
​​
Administration:
Spravato is self-administered as a nasal spray but only under the direct supervision of a healthcare provider in a certified medical setting, due to potential side effects. Patients are monitored for at least two hours after each dose.
Potential side effects can include sedation, dissociation, dizziness, nausea, and increased blood pressure. Because of these effects, it cannot be self-administered at home.
Considerations:
Spravato is typically considered after other antidepressant options have been tried without sufficient improvement. It is not a first-line treatment and is used as part of a broader treatment plan that includes an oral antidepressant.
Understanding How Spravato Works
Most conventional antidepressants target serotonin or norepinephrine pathways. Spravato works differently, acting on NMDA receptors within the brain's glutamate system. Some research suggests this mechanism may influence synaptic plasticity the formation and modification of neural connections though the precise relationship between this activity and Spravato's antidepressant effects is still being studied.
​
This distinct mechanism is part of why Spravato is generally considered for patients who have not achieved adequate improvement with other antidepressant medications, as it offers a different biological approach than what they may have already tried.
​
Who May Be a Candidate for Spravato?
Spravato is FDA-approved for two groups of adult patients:
-
Those with treatment-resistant depression — generally defined as depression that has not responded adequately to at least two different antidepressant medications within the same depressive episode.
-
Those with major depressive disorder who are experiencing acute suicidal ideation or behavior, when Spravato is used alongside an oral antidepressant.
​
Candidacy also depends on practical factors related to how the medication is administered. Because Spravato requires specialized administration and post-dose monitoring, it is available only through healthcare facilities certified under the Spravato Risk Evaluation and Mitigation Strategy (REMS) program, with each dose given under the direct observation of a healthcare provider.
What to Expect During Treatment?
Treatment with Spravato takes place in a controlled clinical setting. During each visit, patients self-administer the nasal spray under the direct guidance of a healthcare provider.
After administration, patients remain at the facility for approximately two hours of monitoring, allowing the care team to observe for side effects and confirm it's safe before leaving. Some
individuals experience temporary effects during this window, including:
-
Dizziness
-
Nausea
-
Dissociation or altered perception
-
Increased blood pressure
-
Drowsiness
​
Because these effects can persist beyond the monitoring period, patients are advised not to drive or operate heavy machinery until the following day, after a full night's sleep.
In terms of scheduling, the initial treatment phase typically involves two sessions per week. From there, dosing frequency is adjusted over time based on individual response and clinical judgment.
Comprehensive Depression Care
Spravato is approved for use in conjunction with an oral antidepressant, and clinical guidance generally recommends it be part of a broader depression treatment plan rather than used as a standalone therapy. Depending on the individual, this may also include psychotherapy and lifestyle interventions such as exercise, sleep regulation, and stress management.
​
Combining multiple approaches allows treatment to address both the biological and psychological/behavioral aspects of depression. Treatment plans are typically developed and adjusted by a patient's healthcare provider based on individual symptoms, history, and response to treatment.