A recent randomized controlled trial (RCT) in New Zealand evaluating the R-107 oral ketamine formulation has shown significant effectiveness in reducing symptoms of depression, including in patients with treatment-resistant depression (TRD). Developed by Douglas Pharmaceuticals, R-107 represents a novel, patent-protected, slow-release ketamine tablet designed for outpatient use. While the trial demonstrated strong antidepressant efficacy, some side effects were noted, prompting further investigation into safety, dosing, and long-term usability.
Study Overview
- Drug Candidate: R-107 (oral slow-release racemic ketamine)
- Location: New Zealand
- Developer: Douglas Pharmaceuticals
- Trial Type: Double-blind, randomized, placebo-controlled trial
- Primary Outcome: Reduction in depressive symptoms measured by standardized psychiatric scales
- Target Population: Adults with major depressive disorder (MDD), including those with TRD
The study was covered by The Sun Ireland and other regional media, signaling growing public and clinical interest in convenient oral alternatives to IV or intranasal ketamine.
Key Findings
1. Significant Reduction in Depression Scores
- Participants receiving R-107 showed statistically significant improvements in mood compared to the placebo group
- Improvements were observed within the first few days of treatment and sustained through the dosing period
- Beneficial effects were particularly notable in those with treatment-resistant profiles, where prior antidepressants had failed
2. Consistent Therapeutic Action
- The slow-release nature of R-107 helped maintain steady plasma concentrations, reducing peak-related side effects and potentially enhancing therapeutic engagement
- Patients reported feeling more emotionally regulated, with reductions in anhedonia and rumination
Side Effects and Safety Observations
While the treatment was generally well-tolerated, several participants experienced side effects, including:
- Nausea
- Mild dizziness
- Fatigue
- Occasional dissociative sensations
No serious adverse events or misuse were reported during the study period. Side effects were dose-dependent and often diminished after the first few doses, suggesting acclimatization.
Clinical Implications
A. Expanding Access to Ketamine Therapy
- Oral formulations like R-107 offer a non-invasive, scalable option for ketamine treatment
- Ideal for outpatient psychiatry, primary care integration, and remote treatment pathways
- May improve adherence and accessibility for patients averse to IV or intranasal delivery
B. A Path Forward for Maintenance Therapy
- R-107 could be used to maintain remission following initial IV ketamine induction
- Especially beneficial for patients in rural settings or with limited clinic access
- Allows more flexible, patient-centered treatment regimens
Scientific Rationale and Pharmacology
- R-107 contains racemic ketamine, targeting both NMDA and AMPA receptor systems
- Promotes neuroplasticity via BDNF and mTOR pathways
- Modulates mood, cognition, and affect regulation circuits in the prefrontal cortex and limbic system
- Oral route may reduce the intensity of psychotomimetic effects while retaining antidepressant activity
Limitations and Future Directions
- Exact dose-response curves and optimal frequency remain under investigation
- Study population was limited to a regional cohort in New Zealand; global trials are needed
- Long-term data on relapse prevention, cognitive effects, and physical tolerability are still pending
Market and Regulatory Outlook
- Douglas Pharmaceuticals aims to continue development into Phase 3 trials
- If approved, R-107 could become the first widely available oral ketamine medication for depression
- May face regulatory comparisons to existing intranasal esketamine (Spravato), but with potential advantages in cost and delivery
Conclusion
The New Zealand RCT of R-107 oral ketamine marks an important step forward in psychiatric pharmacology. With significant antidepressant efficacy and manageable side effects, R-107 has the potential to redefine how ketamine is administered — making treatment more accessible, tolerable, and scalable for patients worldwide. As trials expand, R-107 may emerge as a next-generation solution for depression, especially for those not well-served by existing therapies.
Reference
The Sun Ireland (2024). New oral ketamine pill R-107 shows promise in depression trial. [thesun.ie]
