Extended-release ketamine tablets for treatment-resistant depression: a randomized placebo-controlled phase 2 trial

This phase 2 multicenter clinical trial investigated the efficacy and safety of extended-release ketamine tablets (R-107) in treating treatment-resistant major depression (TRD). 329 patients were screened, 231 entered an open-label enrichment phase (120 mg R-107 daily for 5 days), and 168 responders were randomized to double-blind treatment (placebo, 30, 60, 120, or 180 mg R-107 twice weekly for 12 weeks). The primary endpoint (least square mean change in MADRS at 13 weeks) was met; the 180 mg group showed a statistically significant improvement compared to placebo (-6.1, 95% CI 1.0 to 11.16, P=0.019). Relapse rates showed a dose response (70.6% placebo to 42.9% 180 mg). Tolerability was excellent, with minimal sedation and dissociation. The most common adverse events were headache, dizziness, and anxiety. R-107 tablets were effective, safe, and well-tolerated in this enriched TRD population.

Paul Glue, Colleen Loo, Johnson Fam, Hsien-Yuan Lane, Allan H. Young, Peter Surman