The Association between Intranasal Esketamine and Treatment-emergent Insomnia in the Treatment of Treatment-resistant Major Depression: A Meta-analysis.
Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology August 31, 2025 Cagdas Türkmen, Rutger Boesjes, Anne-Fleur Zandbergen et al.
In adults with treatment-resistant depression, intranasal esketamine added to an antidepressant does not change the likelihood of experiencing insomnia as a side effect compared with placebo. Across seven randomized trials involving 1,311 patients, insomnia was reported by 7.3% of those receiving esketamine and 6.7% of those receiving placebo, a difference that was not statistically significant. This finding contrasts with earlier reports that esketamine improves insomnia symptoms, possibly because adverse-event reporting does not capture gradual improvements in sleep for patients who often have insomnia at the start of treatment.