When standard antidepressants stop working, it can feel like you've run out of options. But treatment-resistant depression — the kind that doesn't respond to two or more medications — now has a targeted medical solution: esketamine (Spravato). At Elevate Psychiatry in Miami, our board-certified psychiatrists offer esketamine treatment for adults who haven't found relief from traditional antidepressants. Here's everything you need to know.
Esketamine is the active S-enantiomer of ketamine — a more potent, more selective form of the compound that has been refined specifically for psychiatric use. Sold under the brand name Spravato, esketamine is administered as a nasal spray in a certified clinical setting and is the first truly new class of rapid-acting antidepressant approved by the FDA in decades.
The FDA has approved Spravato (esketamine) for two specific indications:
Unlike antidepressants that may take four to eight weeks to produce any noticeable effect, esketamine can begin reducing depressive symptoms within hours to days of the first treatment.
Traditional antidepressants — SSRIs, SNRIs, MAOIs — primarily work by modulating serotonin, norepinephrine, or dopamine levels. After years on these medications, the brain's synaptic plasticity in key depression-related circuits can become impaired. This is why, for some people, antidepressants simply stop working or never fully work to begin with.
Esketamine works through an entirely different mechanism: it is an NMDA (N-methyl-D-aspartate) receptor antagonist. NMDA receptors regulate glutamate, the brain's primary excitatory neurotransmitter. By blocking NMDA receptors, esketamine triggers a rapid cascade of events inside neurons — including the release of BDNF (brain-derived neurotrophic factor), which promotes the growth of new synaptic connections in areas like the prefrontal cortex that are damaged or atrophied in chronic depression.
In plain terms: esketamine helps the brain physically rebuild the circuits that regulate mood, motivation, and executive function. This is why patients often describe a lifting of depression that feels qualitatively different from anything an SSRI produced — and why relief can begin far faster.
Patients often ask whether esketamine (Spravato) and ketamine infusions are the same thing. They share the same root compound but differ in important ways:
| Feature | Esketamine (Spravato) | Ketamine Infusion (IV) |
|---|---|---|
| FDA approval for depression | ✅ Yes — TRD and MDD-SI | ❌ Off-label use only |
| Administration | Nasal spray (in-clinic) | IV infusion (in-clinic) |
| Insurance coverage | Medicare, Medicaid, most major plans | Generally not covered (out-of-pocket) |
| REMS certification required | Yes — must be administered at certified site | No formal certification program |
| Monitoring required | 2 hours post-dose | 1–2 hours post-dose |
| Typical cost to patient | Copay (if insured) | $400–$800 per infusion |
Because Spravato is FDA-approved and covered by most insurance plans that include pharmacy benefits, it is often the more accessible option for patients in Miami seeking rapid relief from depression.
At Elevate Psychiatry, our psychiatrists evaluate each patient individually. Generally, esketamine treatment may be appropriate for adults who meet the following criteria:
Patients with bipolar depression may also be considered on a case-by-case basis, in consultation with their treating psychiatrist. A comprehensive psychiatric evaluation is required before beginning esketamine treatment.
Esketamine is one of the most rigorously studied treatments in psychiatry. The FDA approval was supported by the TRANSFORM and SUSTAIN clinical trial programs, which together enrolled thousands of patients across multiple countries.
Key findings from the clinical trials:
These results are why major psychiatric guidelines — including those from the American Psychiatric Association — now recognize esketamine as a legitimate treatment option for TRD, not an experimental one.
Esketamine is not a medication you take home. Every dose is administered under direct medical supervision at our Miami clinic, in compliance with the Spravato REMS (Risk Evaluation and Mitigation Strategy) program. Here's what the process looks like:
For a detailed, step-by-step guide to what happens during a Spravato session — from arrival to discharge — read our full guide: Spravato in Miami: What to Expect at Your Treatment Session.
Esketamine and TMS (Transcranial Magnetic Stimulation) are both FDA-cleared options for patients who haven't responded to antidepressants, but they work differently and suit different patients. Esketamine acts through chemical pathways (glutamate/NMDA), while TMS stimulates specific cortical circuits using magnetic pulses. Speed of onset is a key differentiator: esketamine can produce relief in days, while TMS typically requires a full 6-week course. Some patients benefit from combining both approaches. Read our full comparison: Spravato vs. TMS for Depression: Which Is Right for You?
Elevate Psychiatry is a REMS-certified Spravato treatment center serving Miami, Coconut Grove, Doral, and surrounding South Florida communities. Our psychiatric team includes board-certified psychiatrists who specialize in treatment-resistant depression and who have experience navigating the insurance authorization process for Spravato — including Medicare, Medicaid, and commercial insurers.
We do not operate as a ketamine clinic. Every esketamine treatment is integrated into a comprehensive psychiatric care plan that may include medication management, psychotherapy, and — where appropriate — TMS. This integrated approach helps ensure that esketamine treatment is not just a stand-alone infusion but part of a lasting recovery strategy.
If you or a loved one has been living with depression that hasn't responded to medications, we want to hear from you. Many patients who had given up on feeling better have found real relief with esketamine treatment.
To find out whether esketamine is right for you, call Elevate Psychiatry at (305) 908-1115 or contact us online. We offer same-week psychiatric evaluations and accept most major insurance plans. Our Coconut Grove and Doral locations both offer in-person Spravato treatment sessions.
Related reading: Spravato Treatment in Florida: What You Need to Know | What to Expect at a Spravato Session | Spravato vs. TMS: Which Is Right for You?
