An extended-release oral tablet form of ketamine (R-107) was effective, safe, and well tolerated for treatment-resistant depression. In a phase 2 trial, 231 adults with severe depression took 120 mg of R-107 daily for 5 days; 168 who responded were then randomly assigned to receive 30, 60, 120, or 180 mg of R-107 or placebo twice weekly for 12 weeks. The 180 mg dose produced a significantly greater reduction in depression scores than placebo, with a mean difference of 6.1 points on the MADRS scale. Relapse rates dropped from 70.6% with placebo to 42.9% with 180 mg. No blood pressure changes occurred, and sedation or dissociation were minimal. Most dosing took place at home.
Females with ketamine use disorder have lower leptin levels than healthy females, and those lower levels persist even after two weeks of abstinence. In contrast, males with ketamine use disorder show leptin levels similar to healthy males at the start of abstinence, and their leptin levels increase after two weeks of abstinence. Leptin is a hormone linked to addiction, and these sex-specific differences may be relevant for understanding recovery from ketamine dependence.