In a year-long open-label study of 802 adults with treatment-resistant depression, esketamine nasal spray combined with a new oral antidepressant showed a manageable safety profile and sustained improvement in depressive symptoms. Common side effects included dizziness, dissociation, nausea, and headache, mostly mild or moderate and resolving the same day. Two deaths occurred, neither linked to the drug. Cognitive performance remained stable or improved. Depression scores dropped during the first four weeks and stayed lower through the maintenance phase.
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.