What's Being Reported
A new clinical overview published in Psychiatric Times in April 2026 examines how psychiatrists are approaching treatment-resistant depression (TRD) — a condition where patients have failed to respond to at least two adequate antidepressant trials. The piece highlights esketamine (brand name Spravato), the FDA-approved intranasal ketamine derivative, as a frontline rapid-acting option, particularly for patients experiencing acute suicidal ideation.
The report explores how clinicians weigh patient preferences, systemic access barriers, and the growing body of evidence supporting glutamatergic agents — drugs that work on the brain's glutamate system rather than the serotonin pathways targeted by traditional antidepressants. Esketamine sits at the center of this conversation as the only FDA-approved ketamine-based therapy specifically indicated for TRD and major depressive disorder with suicidal ideation (MDSI).
Why Esketamine Matters for TRD Patients
Treatment-resistant depression affects an estimated 30% of people diagnosed with major depressive disorder — a significant population that has historically had very limited options. Standard antidepressants like SSRIs and SNRIs can take four to six weeks to show effect, and for patients who've already cycled through multiple medications without relief, that waiting period carries real clinical risk.
Esketamine's mechanism is fundamentally different. By targeting NMDA glutamate receptors, it can produce antidepressant effects within hours to days rather than weeks. For someone in acute crisis, that speed matters enormously. The Psychiatric Times piece underscores this, noting that clinicians are increasingly factoring in rapid onset as a core treatment goal — not just symptom reduction over time.
Spravato is administered as a nasal spray in a certified healthcare setting under observation, typically twice weekly for the first month, then tapering. Patients must remain on-site for at least two hours after each session due to potential dissociative side effects. This is a key logistical difference from IV ketamine infusions, which are also done in-office but are administered intravenously and are not FDA-approved for depression (though widely used off-label).
Access Barriers Remain a Real Challenge
Despite its FDA approval and growing clinical endorsement, esketamine is not easily accessible for most patients. The Psychiatric Times overview highlights access as one of the primary friction points clinicians encounter when recommending Spravato.
Cost is a major factor. A single esketamine session can run $800–$1,000 or more without insurance, and while many commercial insurers and Medicare do cover Spravato for qualifying diagnoses, prior authorization hurdles are common and denials are not rare. The requirement that treatment be administered in a certified Risk Evaluation and Mitigation Strategy (REMS) program site also limits geographic availability — not every psychiatric practice or clinic is set up to provide it.
By contrast, IV ketamine infusions are widely available through ketamine clinics across the U.S., but they are almost never covered by insurance, making out-of-pocket costs the norm. For patients trying to choose between these two ketamine-based options, the decision often comes down to insurance coverage (favoring esketamine) versus flexibility and accessibility (often favoring IV ketamine clinics, depending on location).
Key Takeaway for Patients
If you or someone you know has been diagnosed with treatment-resistant depression or is experiencing suicidal thoughts alongside depression, esketamine (Spravato) is worth discussing with a psychiatrist — not just a primary care provider. It's the only FDA-approved ketamine-based option for these specific indications, which means it has the best shot at insurance coverage. However, access to certified providers varies by region, and prior authorization can delay treatment. IV ketamine remains a parallel option worth exploring, especially if Spravato isn't available locally or insurance coverage is denied.
What This Signals for the Ketamine Treatment Landscape in 2026
The continued clinical attention on esketamine for TRD reflects a broader maturation of ketamine-based psychiatry. When Spravato was first approved by the FDA in 2019, skepticism was common — both about efficacy and about whether a dissociative drug could find a sustainable place in mainstream psychiatric care. By 2026, that skepticism has largely given way to practical integration: esketamine is increasingly viewed not as a last resort, but as an early intervention for patients who are unlikely to respond to standard antidepressants.
The Psychiatric Times piece also gestures toward a more patient-centered model of TRD care, where clinician decision-making incorporates patient values, lifestyle, and logistical realities alongside clinical data. That's a shift worth noting. It suggests that the conversation between provider and patient around ketamine is becoming more nuanced — less about whether to use it and more about which form, in what setting, and for how long.
For patients researching their options, this is encouraging. It means the clinical community is catching up to what many patients have already discovered on their own: that conventional antidepressants don't work for everyone, and faster-acting alternatives deserve serious consideration earlier in the treatment process.
Source: Psychiatric Times — Esketamine for Treatment-Resistant Depression
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