Real-World Safety of Esketamine Nasal Spray: A Comprehensive Analysis of Esketamine and Respiratory Depression.
Craig Chepke, Richard C. Shelton, Gerard Sanacora, Teodora Doherty, Palina Tsytsik, Nancy Parker
The International Journal of Neuropsychopharmacology December 1, 2024 DOI: 10.1093/ijnp/pyae058 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective analysis of pharmacovigilance data Peer reviewed |
|---|---|
| Sample size | 50 |
| Population | Patients with respiratory depression events associated with esketamine use in postmarketing surveillance databases |
| Intervention | Esketamine nasal spray |
| Duration | 47 months of postapproval data |
| Topics | Depression Esketamine Ketamine |
| Keywords | Respiratory depression Depression treatment Esketamine therapy Psychiatric medicine Drug safety Clinical research |
| Citations | 7 |
| Key points | Respiratory depression is infrequent with esketamine treatment in the postmarketing setting, with an estimated incidence of 1 case per 20,000 treatment sessions. |
Abstract
Esketamine nasal spray (ESK) is approved, in conjunction with an oral antidepressant, for the treatment of treatment-resistant depression in adults and for the treatment of depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. No adverse events (AEs) of respiratory depression were reported in ESK phase 3 clinical trials; however, postmarketing incidents of respiratory depression associated with ESK use have been observed. The Janssen Global Medical Safety (GMS) database was reviewed for cases meeting the criteria for respiratory depression with ESK using 47 months of postapproval data, based on the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ) acute central respiratory depression (broad). FDA Adverse Event Reporting System (FAERS), EudraVigilance, and literature searches were performed to identify reports of respiratory depression related to ESK use. Fifty cases, representing 50 patients, in the GMS database met the case definition for respiratory depression; 8 of these had a stronger association with ESK use. The MedDRA preferred term (PT) hypopnea met the threshold for disproportionality with ESK in FAERS. The MedDRA PTs asphyxia, oxygen saturation decreased, respiratory depression, and apnea met the threshold for disproportionality with ESK in EudraVigilance. Despite extensive soliciting of AEs for ESK with the US Risk Evaluation and Mitigation Strategy program, respiratory depression is infrequently observed with ESK treatment in the postmarketing setting (estimated incidence: 1 case per 20 000 treatment sessions). Symptoms are manageable and resolve with minor supportive measures. Monitoring for symptoms of respiratory depression, including pulse oximetry, is recommended within the postdose observation period.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.
Citations in the library
Cited by 4
- Intranasal esketamine: real-world clinical practice in treatment-resistant depression and factors associated with treatment response. BMC Psychiatry March 17, 2026
- Ketamine pharmacotherapy for major depressive disorder: A narrative review Progress in Neuro-Psychopharmacology and Biological Psychiatry February 27, 2026
- Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis. Pharmaceuticals May 9, 2025
- ADVERSE EFFECTS OF ESKETAMINE IN TREATMENT RESISTANT DEPRESSION: A COMPREHENSIVE LITERATURE REVIEW (2020-2025) International Journal of Innovative Technologies in Social Science February 16, 2026
Cites 7
- 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 of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
- 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
- Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation With Intent The Journal of Clinical Psychiatry May 11, 2020
and 2 more in the library