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Extended-Release Oral Ketamine Effective for Treatment-Resistant Depression

Medically reviewed by Carmen Pope, BPharm. Last updated on July 17, 2024.

By Elana Gotkine HealthDay Reporter

WEDNESDAY, July 17, 2024 -- For patients with treatment-resistant depression, racemic ketamine, given as an extended-release tablet (R-107), administered orally, is effective, safe, and well tolerated, according to a study published online June 24 in Nature Medicine.

Paul Glue, M.D., from the University of Otago in Dunedin, New Zealand, and colleagues examined the safety and tolerability of racemic ketamine given orally compared with other routes of administration in a phase 2 multicenter clinical trial. A total of 231 male and female patients with treatment-resistant depression and Montgomery-Asberg Depression Rating Scale (MADRS) scores ≥20 received R-107 tablets (120 mg) for five days and were assessed on day 8. One hundred sixty-eight responders on day 8 were randomly assigned to receive double-blind R-107 doses of 30, 60, 120, or 180 mg or placebo, twice weekly for a further 12 weeks in a 1:1:1:1:1 ratio.

The researchers found that the primary objective was met; at 13 weeks, the least-squares mean difference of the MADRS score for the 180-mg tablet group and placebo was −6.1 (95 percent confidence interval 1.0 to 11.16; P = 0.019). During double-blind treatment, relapse rates showed a dose response, from 70.6 percent for placebo to 42.9 percent for the 180-mg dose. There was excellent tolerability noted, with no blood pressure changes, minimal reports of sedation, and minimal dissociation. Headache, dizziness, and anxiety were the most common adverse events.

"Use of an extended-release oral dosage ketamine formulation may be advantageous compared with intranasal or intravenous dosing, in terms of reduced intensity of dissociation, lower risk of abuse, reduced frequency and intensity of sedative and cardiovascular side effects, and improved convenience for administration in the community," the authors write.

Several authors disclosed ties to biopharmaceutical companies, including Douglas Pharmaceuticals, which is developing extended-release racemic ketamine and funded the study.

Abstract/Full Text

Disclaimer: Statistical data in medical articles provide general trends and do not pertain to individuals. Individual factors can vary greatly. Always seek personalized medical advice for individual healthcare decisions.

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