Extended-Release Ketamine Effective for Treatment-Resistant Depression

Recent research has highlighted that for individuals suffering from treatment-resistant depression, racemic ketamine administered as an extended-release tablet (R-107) is both effective and safe. This study, which was published online in Nature Medicine on June 24, details that the oral administration of this medication shows promising results in terms of safety and patient tolerance.

The study, led by Dr. Paul Glue from the University of Otago in Dunedin, New Zealand, focused on comparing the safety and tolerability of orally administered racemic ketamine with other methods of administration. This phase 2 multicenter clinical trial included 231 male and female participants, all of whom had treatment-resistant depression and Montgomery-Asberg Depression Rating Scale (MADRS) scores of 20 or higher. These participants received R-107 tablets at a dosage of 120 mg for five days and were later assessed on the eighth day.

On day 8, 168 responders were selected and randomly assigned to receive double-blind doses of R-107 at 30, 60, 120, or 180 mg, or a placebo, twice weekly for an additional 12 weeks. The participants were divided in a 1:1:1:1:1 ratio for this part of the study.

The primary goal of the study was achieved. By the 13th week, the least-squares mean difference in MADRS scores between the 180-mg tablet group and the placebo group was -6.1, with a 95 percent confidence interval ranging from 1.0 to 11.16, and a P-value of 0.019. During the double-blind treatment phase, there was a noticeable dose-response relationship in relapse rates, ranging from 70.6 percent for the placebo group to 42.9 percent for those receiving the 180-mg dose.

The tolerability of R-107 was highly favorable. There were no significant changes in blood pressure, and reports of sedation and dissociation were minimal. The most commonly reported adverse events included headaches, dizziness, and anxiety.

The study’s authors suggest that using an extended-release oral ketamine formulation presents several advantages over intranasal or intravenous methods. These advantages include a reduction in the intensity of dissociation, a lower risk of abuse, decreased frequency and intensity of sedative and cardiovascular side effects, and improved convenience for community administration.

It is worth noting that several authors of the study disclosed connections to biopharmaceutical companies, including Douglas Pharmaceuticals. This company is currently developing extended-release racemic ketamine and funded the study.

This new oral formulation of racemic ketamine shows promise in providing a safer, more convenient alternative for patients with treatment-resistant depression, potentially improving their quality of life significantly.