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.
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.
A 26-year-old man who abused ketamine by inhalation for 12 months developed manic-like symptoms after using the drug. This case suggests a possible relationship between manic symptoms and ketamine abuse, and may be the first report of mania following recreational ketamine use.
A review compares the antidepressant mechanisms of sarcosine, benzoate, ketamine, esketamine, and arketamine. These compounds modulate N-methyl-d-aspartate glutamate receptors (NMDARs) and reduce brain inflammation by inhibiting microglial activity. Though they act differently as antagonists or coagonists of NMDARs, all have shown efficacy in animal models or human trials. The review concludes that these drugs act as both NMDAR modulators and anti-inflammatory agents, making them potentially effective for treating depression.