Efficacy and Safety of Esketamine Nasal Spray in Treatment-Resistant Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
medRxiv September 25, 2025 B Gowthami, Ishita Mehta, Sneha Baiju et al. 1 citation preprint
Adding esketamine nasal spray to an oral antidepressant improves treatment response, remission, and daily functioning in people with treatment-resistant depression, but it also raises the risk of dissociation and hypertension. A systematic review pooled data from 17 randomized controlled trials involving 10,073 patients. Esketamine plus an antidepressant roughly doubled the odds of achieving a 50% reduction in depressive symptoms and nearly tripled the odds of remission compared to placebo plus an antidepressant. Functional disability scores also improved more with esketamine. However, continuous measures of depression severity showed no statistically significant difference between groups. Safety analysis found that dissociation was about twice as likely and hypertension about 40% more likely with esketamine, while sedation and nausea risks were not significantly elevated.