A new analysis of nine randomized controlled trials involving 1,449 patients with treatment-resistant depression found that esketamine, given as a nasal spray or intravenously, improved clinical response rates. Patients receiving esketamine were nearly twice as likely to respond compared to those in the control group.
However, the analysis also revealed that esketamine significantly increased the risk of nine adverse events, including nausea, dissociation, dizziness, vertigo, elevated blood pressure, and drowsiness. These side effects were dose-dependent, meaning higher doses led to greater risks. For example, high-dose esketamine carried a nearly 11-fold higher risk of dissociation, while low-dose had about a 3-fold increase.
Treatment discontinuation due to side effects was also 2.22 times higher with esketamine. The study did not report serious adverse events or long-term follow-up.
Because this is a meta-analysis of existing trials, the results are pooled estimates. The findings suggest that doctors should carefully balance the benefits and risks when prescribing esketamine, using personalized dosing strategies. Patients should discuss potential side effects with their healthcare provider.