655. EXPANDING ACCESS TO KETAMINE THROUGH REFORMULATION
International Journal of Neuropsychopharmacology August 1, 2025 DOI: 10.1093/ijnp/pyaf052.397 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Phase 2 multicenter randomized controlled trial with open-label enrichment phase Double-blind Peer reviewed |
|---|---|
| Sample size | 231 |
| Population | Adult patients with treatment-resistant depression and MADRS scores of 20 or higher |
| Dose | 120 mg per day for 5 days (open-label phase); 30, 60, 120, or 180 mg twice weekly for 12 weeks (double-blind phase) |
| Duration | 5-day open-label enrichment phase followed by 12 weeks of double-blind treatment, with assessment at 13 weeks |
| Measures | Montgomery–Asberg Depression Rating Scale (MADRS) |
| Topics | Esketamine Ketamine |
| Key findings | Extended-release ketamine tablets were acutely effective in 73% of patients with treatment-resistant depression within one week. During 12 weeks of double-blind maintenance, the 180 mg twice-weekly dose produced a least squares mean MADRS difference of -6.1 versus placebo (95% CI 1.0-11.16; P=0.019), with relapse rates declining from 70.6% on placebo to 42.9% at 180 mg. The authors report minimal dissociation and sedation and mostly at-home dosing. |
Abstract
Abstract Background Ketamine, a rapidly acting antidepressant, requires dosing in clinic because of strong symptoms of dissociation and sedation after IV/IN dosing. This need for dosing in clinic limits capacity to treat patients with Treatment Resistant depression (TRD). We hypothesize that ketamine formulations that maximize ketamine’s first pass metabolism and delay absorption will have improved tolerance 1 and could permit dosing at home. Aims & Objectives To evaluate the safety, tolerability and efficacy of an extended-release racemic ketamine tablet in patients with TRD (R-107, developed by Douglas Pharmaceuticals).
Method: In this phase 2 multicenter clinical trial, adult patients with TRD and Montgomery–Asberg Depression Rating Scale (MADRS) scores ≥20 received open-label R-107 tablets 120 mg per day for 5 days and were assessed on day 8 (enrichment phase). On day 8, responders (MADRS scores ≤12 and reduction ≥50%) were randomized on a 1:1:1:1:1 basis to receive double-blind R-107 doses of 30, 60, 120 or 180 mg, or placebo, twice weekly for a further 12 weeks. Nonresponders on day 8 exited the study.
Results: 231 patients entered the open-label enrichment phase (days 1–8) and 168 responders were randomized to double-blind treatment. The primary objective was met; the least square mean difference of MADRS score for the 180 mg tablet group and placebo was −6.1 (95% confidence interval 1.0-11.16, P = 0.019) at 13 weeks. Relapse rates during double-blind treatment showed a dose response from 70.6% for placebo to 42.9% for 180 mg. Tolerability was excellent, with no changes in blood pressure, minimal reports of sedation and minimal dissociation. Most patient dosing occurred at home 2. Discussion & Conclusions Extended-release ketamine tablets were acutely effective in 73% of patients with TRD within 1 week. Maintenance of this antidepressant activity was greatest in those receiving 180mg twice weekly over the next 3 months. As predicted, dissociation was minimal, tolerability was good, and most dosing occurred at home. This would expand access to ketamine treatment to a greater number of patients with TRD.