Extended-Release Ketamine Tablets: Phase 2 Trial Results
One of the longstanding challenges with ketamine therapy has been finding the right delivery method — one that preserves the drug's antidepressant power while minimizing side effects and making treatment accessible. A Phase 2 randomized controlled trial published in Nature Medicine in 2024 tested a novel approach: an extended-release oral ketamine tablet known as R-107. The results mark an important step forward for patients with treatment-resistant depression (TRD).
What the Study Tested
The trial evaluated R-107, an extended-release formulation of racemic ketamine designed to be swallowed as a standard tablet. Unlike sublingual troches or intravenous infusions, extended-release tablets deliver ketamine gradually through the gastrointestinal tract. This slower absorption profile was hypothesized to maintain antidepressant efficacy while reducing the acute dissociative and cardiovascular effects that can accompany faster-acting formulations.
Participants in the study had confirmed treatment-resistant depression, meaning they had failed to respond adequately to at least two prior antidepressant treatments. They were randomized to receive either the R-107 extended-release ketamine tablet or placebo over the course of the trial period, with depression severity measured using standardized rating scales.
Key Findings
The results were encouraging on multiple fronts. Patients receiving the extended-release ketamine tablets showed statistically significant improvement in depressive symptoms compared to the placebo group. Importantly, these improvements emerged within the first few weeks of treatment and were sustained throughout the study period.
From a safety perspective, the extended-release formulation performed notably well. Unlike IV ketamine or even some sublingual formulations, R-107 produced minimal dissociative symptoms. Blood pressure changes — a common concern with ketamine administration — were negligible. Sedation was mild and transient. The overall tolerability profile was strong, with most participants completing the trial without significant adverse events.
Why Extended-Release Matters
The significance of this trial goes beyond the specific numbers. It validates oral ketamine as a viable route of administration for depression treatment, which has practical implications for how and where patients can receive care.
IV ketamine infusions require patients to visit a clinic, often multiple times per week, at considerable cost. Nasal esketamine (Spravato) similarly requires in-office administration and monitoring. An oral tablet that patients could eventually take at home — under appropriate medical supervision — would dramatically expand access to ketamine therapy, particularly for patients in rural areas or those with mobility limitations.
The extended-release mechanism specifically addresses the concern that oral ketamine's side effect profile might limit its usefulness. By smoothing out the absorption curve, R-107 appears to deliver therapeutic benefit without the peaks in blood concentration that drive dissociation and cardiovascular changes.
How This Compares to Current Oral Ketamine Options
At Isha Health, we currently use sublingual ketamine troches as our primary at-home treatment modality. Sublingual administration offers faster absorption than a swallowed tablet, which means patients experience some degree of dissociation — an effect that many clinicians and patients actually consider therapeutic when properly supported with psychotherapy integration.
The extended-release tablet represents a different point on the spectrum: potentially less dissociation, potentially more convenient for certain patients, but also a formulation that is not yet commercially available. R-107 remains in clinical development and would need to complete Phase 3 trials before seeking FDA approval.
For patients considering their options today, sublingual ketamine remains the most well-studied and accessible oral formulation. The comparison between oral ketamine and IV infusion highlights the practical advantages of at-home treatment, and Isha Health's clinical outcomes demonstrate strong real-world effectiveness with the sublingual approach.
What Comes Next
Phase 3 trials for R-107 will need to confirm these findings in larger, more diverse patient populations. Researchers will also be looking at optimal dosing, long-term safety, and how the extended-release formulation performs across different patient subgroups.
For a broader overview of how ketamine therapy works and what to expect, see our complete guide to ketamine therapy. If you are interested in exploring at-home ketamine treatment, learn more about Isha Health's online ketamine therapy program.
Related Articles
Considering ketamine therapy? Isha Health offers physician-led at-home treatment with an 88.8% improvement rate. Check appointment availability.
88.8% of Isha Health patients with moderate-to-severe depression show measurable improvement
Based on 546 patients and 1,900+ validated assessments. See our clinical outcomes →
