Dose-dependent adverse events of esketamine in treatment-resistant depression: a systematic review and meta-analysis of randomized controlled trials.
Frontiers in pharmacology January 1, 2026 Yang Qu, Shujin Li, Li Tian et al.
A meta-analysis of nine randomized controlled trials involving 1,449 patients found that esketamine improves symptoms in treatment-resistant depression but significantly increases dose-dependent adverse events. Compared with controls, esketamine raised the risk of nine adverse events including nausea, dissociation, dizziness, vertigo, elevated blood pressure, and somnolence. Risks were strongly dose-dependent: the high-dose group (≥56 mg or 0.40 mg/kg) had a greater risk than the low-dose group (≤28 mg or 0.20 mg/kg), with relative risk for nausea of 3.72 versus 1.69 and for dissociation of 10.65 versus 3.27. Although esketamine improved clinical response rate (relative risk = 1.94), it increased treatment discontinuation due to adverse events by 2.22-fold. Clinical use should adopt personalized dosing strategies balancing efficacy and tolerability.