Subcutaneous (SC) ketamine shows promise as a rapid and effective antidepressant for unipolar and bipolar depression, with response and remission rates ranging from 50 to 100% after single or multiple doses. Doses of 0.1 to 0.5 mg/kg of racemic ketamine and 0.5 to 1 mg/kg of esketamine were used, administered weekly or twice-weekly, often with dose titration. Side effects were temporary. This systematic review of 12 studies (two randomized trials, five case reports, and five retrospective studies) found SC ketamine to be a convenient and cost-effective route, particularly relevant for developing countries, though a meta-analysis was not possible due to heterogeneity. Further research comparing SC with intravenous and intranasal protocols is needed.
In a small group of eight patients with treatment-resistant depression, six months of adjunctive esketamine nasal spray was associated with improvements in attention, memory, and several executive functions, including working memory, set-shifting, and inhibitory control. Most cognitive gains appeared by three months, though working memory and set-shifting improvements were significant only at six months. Depression severity also decreased over the six-month period, and most cognitive improvements correlated with reduced depression severity. No cognitive decline was observed. The authors note that confirmatory studies are needed.