Study: Ketamine Relieves Treatment-Resistant Depression

What the Research Is Saying

A new report from The Jerusalem Post, published June 28, 2026, highlights emerging research on ketamine's ability to relieve treatment-resistant depression (TRD) and reduce suicidal thoughts — conditions that traditional antidepressants often fail to address adequately.

The headline's reference to ketamine as a "party drug" reflects the substance's complicated public image. Ketamine has been used recreationally for decades, and that association has historically slowed its adoption in psychiatry. But the clinical picture has been shifting significantly. In 2019, the U.S. Food and Drug Administration approved esketamine (Spravato), a nasal spray derived from ketamine, specifically for treatment-resistant depression and major depressive disorder with acute suicidal ideation. Research interest in oral and tablet forms of ketamine has grown steadily alongside that approval.

Treatment-resistant depression is generally defined as depression that has not responded to at least two adequate trials of antidepressant therapy. It represents a serious and often debilitating subset of major depressive disorder, and patients in this category face significantly higher risks of chronic impairment and suicidal ideation. That's precisely why researchers and clinicians have been willing to look at a compound with an unconventional background: for many patients, conventional options simply are not working.

Why This Matters for Oral Ketamine and Tablet Users

Most of the clinical research driving headlines about ketamine and depression has been conducted using intravenous (IV) infusions or intranasal esketamine. These delivery methods produce rapid, predictable plasma levels and have well-documented protocols. Oral ketamine tablets and sublingual troches, by contrast, are typically prescribed off-label by clinicians and compounding pharmacies, and they operate through a meaningfully different pharmacological pathway.

When ketamine is taken orally, it undergoes first-pass metabolism in the liver. This process converts a significant portion of the active ketamine into norketamine before it reaches systemic circulation, which reduces the overall bioavailability compared to IV administration — estimates typically range from roughly 16 to 30 percent for oral formulations. The result is a slower onset, a longer but gentler duration, and a lower peak plasma concentration than IV or intranasal routes.

For patients using tablets as part of a supervised at-home protocol, this pharmacokinetic profile has practical consequences. The antidepressant effects observed in infusion-based research may not translate directly in terms of dose or timing when moving to oral formats. Clinicians prescribing oral ketamine generally work with patients to calibrate dosing based on individual response, body weight, and tolerance — not simply by scaling down an IV dose.

The growing body of evidence tying ketamine to improvements in treatment-resistant depression and suicidal ideation does, however, strengthen the broader clinical rationale for oral formulations. While tablet ketamine is not FDA-approved for these indications, physicians can prescribe it off-label when they judge the benefit-risk profile appropriate for a specific patient. Research like that covered by The Jerusalem Post reinforces the mechanism of action — ketamine's effect on NMDA receptors and its rapid modulation of glutamate signaling — which applies regardless of delivery route.

Comparing Delivery Methods: Tablets, Troches, and Infusions

Patients navigating ketamine treatment options often encounter a spectrum of delivery formats, and understanding the trade-offs is important for setting realistic expectations.

IV infusions remain the most studied format and produce the most reliable plasma concentrations. They require clinical supervision, are typically administered in a clinic setting over 40 to 60 minutes, and can be expensive without insurance coverage. They are generally considered the reference standard in research contexts.

Intranasal esketamine (Spravato) is FDA-approved for TRD and must be administered in a certified healthcare setting with a two-hour observation window. It's the only ketamine-derived product with a specific regulatory approval for depression, which affects insurance reimbursement significantly.

Sublingual troches dissolve under the tongue and are absorbed partially through the oral mucosa, bypassing some first-pass metabolism. Bioavailability sits higher than purely swallowed tablets, and onset is typically faster. They are a common compounded format for at-home use under medical supervision.

Oral tablets are swallowed and fully subject to first-pass metabolism. They offer the most straightforward administration — no preparation, no special technique — and can support consistent, low-dose protocols. Some clinicians use them for maintenance phases after an initial infusion series, or as the primary treatment modality for patients who prefer at-home access and tolerate a gentler dose curve.

None of the oral or troche formats are FDA-approved for depression specifically. Patients using them should be doing so within a supervised clinical relationship, with clear protocols for dose escalation, contraindications, and monitoring.

What to Watch Going Forward

The continued publication of research tying ketamine to meaningful outcomes in treatment-resistant depression and suicidal ideation carries implications beyond individual patient care. It shapes how payers, regulators, and health systems think about reimbursement and access — and access is one of the most significant practical barriers for patients who could benefit.

IV infusions can cost several hundred to over a thousand dollars per session without insurance, and a typical initial series involves multiple sessions. Spravato has navigated the reimbursement landscape with FDA approval, but coverage remains inconsistent. Oral and compounded formats are often less expensive per dose, but they sit in a less well-defined regulatory space and are not covered by most insurance plans.

As research accumulates and clinical consensus solidifies, there is a plausible pathway toward broader recognition of oral ketamine as a legitimate treatment modality — particularly for maintenance use or for patients in areas without easy access to infusion clinics. That won't happen quickly, but each credible study reported in outlets like The Jerusalem Post contributes to the evidence base that regulators, payers, and clinical guidelines eventually respond to.

For patients currently using or considering ketamine tablets for depression that hasn't responded to standard treatments, the practical advice is consistent: pursue treatment through a licensed clinician familiar with ketamine protocols, ensure your psychiatric team is aware of and coordinating with your ketamine provider, and monitor your response carefully with structured check-ins. The science supporting ketamine's role in hard-to-treat depression is getting stronger — and oral formats are a meaningful part of how that treatment reaches patients who need it.