Benefit–Risk Assessment of Esketamine Nasal Spray vs. Placebo in Treatment‐Resistant Depression
Eva G. Katz, David Hough, Teodora Doherty, Rosanne Lane, Jaskaran Singh, Bennett Levitan
Clinical Pharmacology & Therapeutics August 29, 2020 DOI: 10.1002/cpt.2024 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Post hoc analysis Peer reviewed |
|---|---|
| Population | Patients with treatment-resistant depression |
| Interventions | Esketamine nasal spray oral antidepressant |
| Topics | Depression Esketamine |
| Keywords | Adverse effect Maintenance therapy Placebo Nasal spray Depression economics Antidepressant Anesthesia Nasal administration Pharmacology Chemotherapy |
| Citations | 35 |
| Key points | Esketamine nasal spray plus an oral antidepressant shows a positive benefit-risk profile for induction and maintenance treatment of treatment-resistant depression. |
Abstract
This post hoc analysis assessed the benefit-risk profile of esketamine nasal spray + oral antidepressant (AD) induction and maintenance treatment in patients with treatment-resistant depression (TRD). The Benefit-Risk Action Team framework was utilized to assess the benefit-risk profile using data from three induction studies and one maintenance study. Benefits were proportion of remitters or responders in induction studies and proportion of stable remitters or stable responders who remained relapse-free in the maintenance study. Risks were death, suicidal ideation, most common adverse events (AEs), and potential long-term risks. Per 100 patients on esketamine + AD vs. AD + placebo in induction therapy, 5-21 additional patients would remit and 14-17 additional patients would respond. In maintenance therapy, 19-32 fewer relapses would occur with esketamine. In both cases, there was little difference in serious or severe common AEs (primarily dissociation, vertigo, and dizziness). These findings support a positive benefit-risk balance for esketamine + AD as induction and maintenance treatment in patients with TRD.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.
Citations in the library
Cited by 16
- Long-term safety of ketamine and esketamine in treatment of depression Expert Opinion on Drug Safety April 13, 2022
- Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis. American Journal of Psychiatry March 1, 2025
- Overcoming the myths of esketamine administration: different and not difficult Frontiers in Psychiatry November 23, 2023
- Esketamine alleviates cognitive impairment signs induced by modified electroconvulsive therapy in a depression rat model via the KLF4/p38 MAPK pathway. Journal of Affective Disorders May 1, 2025
- Efficacy and Safety of Esketamine Nasal Spray in Treatment-Resistant Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials medRxiv September 25, 2025
and 11 more in the library
Cites 5
- 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 Plus Oral Antidepressant in Patients With Treatment-Resistant Depression The Journal of Clinical Psychiatry April 20, 2020
- Patient preferences for ketamine-based antidepressant treatments in treatment-resistant depression: Results from a clinical trial and panel Neurology Psychiatry and Brain Research September 1, 2020