The Association between Intranasal Esketamine and Treatment-emergent Insomnia in the Treatment of Treatment-resistant Major Depression: A Meta-analysis.
Cagdas Türkmen, Rutger Boesjes, Anne-Fleur Zandbergen, Jeanine Kamphuis, Wolfgang Viechtbauer, Robert A Schoevers, Jens H van Dalfsen
Clinical Psychopharmacology and Neuroscience August 31, 2025 DOI: 10.9758/cpn.25.1271 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Meta-analysis Randomized Placebo-controlled Peer reviewed |
|---|---|
| Sample size | 1,311 |
| Population | Adult patients (aged ≥ 18 years) with a primary diagnosis of major depressive disorder and treatment-resistant depression |
| Topics | Depression Esketamine |
| Keywords | Adverse drug event Depressive disorder, major Esketamine: esketamine New treatment Insomnia Sleep benefit Side effect Meta-analysis: meta-analysis Trials Placebo |
| Key findings | Intranasal esketamine compared with placebo was not associated with the odds of insomnia as an adverse event (OR = 1.07; 95% CI = 0.68-1.69; p = 0.76). |
Abstract
Intranasal (IN) esketamine represents a novel add-on treatment for treatment-resistant depression (TRD) with reported favourable effects on insomnia. IN esketamine treatment might similarly reduce the incidence of insomnia as an adverse event (AE). The present meta-analysis therefore investigated whether IN esketamine relative to placebo is associated with a lower incidence of insomnia as an AE in adults with TRD. Data were retrieved from seven randomised placebo-controlled trials evaluating the safety and efficacy of IN esketamine combined with a monoaminergic antidepressant in the treatment of TRD that reported data on insomnia as an AE. The study population (n = 1,311) comprised adult patients (aged ≥ 18 years) with a primary diagnosis of major depressive disorder. A mixed-effects logistic regression model was employed to compare the incidence of insomnia as an AE between the IN esketamine and placebo group. Insomnia as an AE was reported by 52 patients (7.3%) in the IN esketamine group relative to 40 (6.7%) in the placebo group. IN esketamine compared to placebo was not associated with the odds of insomnia as an AE (OR = 1.07; 95% CI = 0.68-1.69; p = 0.76). There was no evidence for heterogeneity between the included trials. IN esketamine does not affect the occurrence of insomnia as an AE in the treatment of TRD. This contrasts previous findings demonstrating beneficial effects of esketamine on insomnia severity relative to placebo, although AE reporting may not capture insomnia improvements in a population with frequent baseline insomnia.
Comparable studies
Other systematic reviews and meta-analyses on esketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Adults with unipolar or bipolar major depression | 2020 | Systematic review and meta-analysis | n = 1,877 |
| The acute antisuicidal effects of single-dose intravenous ketamine and intranasal esketamine in individuals with major depression and bipolar disorders: A systematic review and meta-analysis. Participants in randomized controlled trials of ketamine for suicidal ideation | 2020 | Systematic review and meta-analysis | n = 197 |
| Efficacy of Esketamine Augmentation in Major Depressive Disorder Patients with major depressive disorder who are treatment-resistant or acutely suicidal | 2020 | Systematic review and meta-analysis | n = 774 |
| Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis. Patients with treatment-resistant major depressive disorder | 2025 | Systematic review and meta-analysis | |
| EFFICACY AND SAFETY OF RACEMIC KETAMINE AND ESKETAMINE FOR DEPRESSION: A SYSTEMATIC REVIEW AND META-ANALYSIS Adults with unipolar or bipolar major depression | 2022 | Systematic review and meta-analysis | n = 2,903 |
Citations in the library
Cites 14
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study American Journal of Psychiatry April 16, 2018
- Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) The International Journal of Neuropsychopharmacology July 9, 2019
- Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients With Major Depressive Disorder Who Have Active Suicide Ideation With Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II) The International Journal of Neuropsychopharmacology August 26, 2020
and 9 more in the library