What the Research Says
A clinical review published in Psychiatric Times in April 2026 takes a close look at how clinicians are navigating treatment-resistant depression (TRD) — a condition affecting roughly one-third of people diagnosed with major depressive disorder who don't respond to two or more antidepressant trials. The piece centers on esketamine (Spravato), the FDA-approved intranasal formulation of ketamine's S-enantiomer, and examines why clinicians reach for glutamatergic agents like it when conventional options fail. It also surfaces something many patients already feel firsthand: access barriers remain a significant friction point in getting fast-acting care. Read the original article at Psychiatric Times.
The review emphasizes that patient preferences — including treatment setting, frequency of visits, and tolerance for side effects — play a meaningful role in clinical decision-making. This is a notable shift. For years, TRD treatment was largely provider-driven; the recognition that patient workflow matters is reshaping how care is structured in 2026.
Where Ketamine Troches Fit Into This Picture
Esketamine nasal spray and ketamine troches are not the same thing — but they're frequently compared by patients exploring their options, and the Psychiatric Times review gives us useful context for understanding the tradeoffs.
Esketamine (Spravato) is FDA-approved specifically for TRD and major depressive disorder with acute suicidal ideation. It's administered in a clinical setting under observation, typically twice weekly for the first month, then tapering to weekly or biweekly sessions. That structure offers medical supervision and a well-documented safety profile — but it also means repeated clinic visits, REMS program enrollment, and out-of-pocket costs that can reach hundreds of dollars per session for those without compatible insurance coverage.
Ketamine troches — sublingual or buccal lozenges compounded from racemic ketamine — occupy a different lane. They're not FDA-approved for depression as a standalone indication, but they are legally prescribed off-label and compounded by licensed pharmacies. The practical difference for patients is significant: troches are taken at home, on a clinician-directed schedule, without requiring a supervised clinical session for each dose. For someone managing a demanding job, childcare, or limited transportation, that flexibility isn't a minor convenience — it's often the difference between consistent treatment and dropping out of care.
The review's focus on rapid glutamatergic action is worth noting for troche users as well. Racemic ketamine, the compound in troches, acts on the same NMDA receptor pathway as esketamine. Early response data — including reductions in depressive symptoms within hours to days — applies broadly to the ketamine class, not exclusively to the nasal formulation. Some patients who've tried both report that troche regimens, when dosed correctly and consistently, provide comparable relief with fewer logistical hurdles.
Key Takeaway
Esketamine remains the only FDA-approved ketamine-based treatment for TRD, but compounded ketamine troches offer a legitimate, clinician-supervised at-home alternative for many patients. The right choice depends on your diagnosis, access to care, insurance coverage, and how your provider weighs supervised versus home-based treatment. Talk openly with your prescriber about which format fits your real-world routine — adherence matters more than format.
Access Barriers and What They Mean for Compounding
One of the more practically important threads in the Psychiatric Times piece is its acknowledgment that access barriers — cost, geography, provider availability, and REMS requirements — are real obstacles in TRD care. This is not new information for anyone who has tried to schedule Spravato sessions in a rural area or received a denial from a commercial insurer. But seeing it named explicitly in a clinical publication matters, because it legitimizes what many patients and prescribers already navigate through compounded ketamine.
Compounding pharmacies fill a structural gap in the ketamine landscape. When clinic-based esketamine isn't feasible, a troche prescription from a licensed provider — paired with a reputable compounding pharmacy — gives patients access to the same core therapeutic mechanism in a more sustainable format. In 2026, with telehealth prescribing of controlled substances still under regulatory scrutiny, patients should be aware that legitimate troche prescriptions require an in-person or qualifying telehealth evaluation, and that the compounding pharmacy should be PCAB-accredited or operating under state board oversight.
Dosing also deserves attention here. Troche doses vary — commonly between 100mg and 400mg of racemic ketamine per lozenge — and the bioavailability of sublingual ketamine is meaningfully different from intranasal esketamine. This means that dose comparisons between the two formats aren't straightforward, and self-adjusting troche doses based on what you've read about Spravato protocols is not advisable. Your prescribing clinician should be guiding titration based on your response and tolerability, not a generic protocol.
The Bigger Trend: Patient-Centered TRD Care
What's most encouraging about the direction reflected in this review is the growing clinical consensus that patient preferences are a legitimate clinical variable in TRD treatment planning. Speed of response matters. Tolerability matters. But so does whether a patient can realistically show up for care — and sustain it over months, not just weeks.
Ketamine troches have found their place in this landscape not by competing with esketamine on clinical trial data, but by meeting patients where infusion clinics and REMS-enrolled practices often can't. As the evidence base for at-home ketamine continues to develop, and as regulators and payers slowly adjust to the realities of TRD care delivery, troches are likely to remain a core tool for clinicians prioritizing both efficacy and real-world adherence.
If you're currently in a troche protocol and wondering whether esketamine would be more effective for you, the honest answer is: it depends. Both are valid. Both carry risks. Both require clinical oversight. The best path is a direct conversation with a provider who knows your history and can weigh the tradeoffs without a financial stake in either option.
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