Oral Prolonged-Release Ketamine for Treatment-Resistant Depression: Two Randomized Clinical Trials.
JAMA network open June 1, 2026 Martin Walter, Christine Zu Eulenburg, Ani Damyanova et al. 1 citation
A novel oral prolonged-release ketamine tablet, KET01, produced minimal dissociative and cardiovascular side effects compared to intranasal esketamine, which caused significant dissociation. In a phase 2 trial for treatment-resistant depression, the primary endpoint at 21 days was not met; the difference in Montgomery-Åsberg Depression Rating Scale (MADRS) score for 240 mg/day KET01 versus placebo was -1.82 points, not statistically significant. However, early reductions in depression scores were observed at 7 hours and at days 4 and 7. The antidepressant properties and tolerability support further development of KET01 for at-home use.