The efficacy and safety of adjunctive intranasal esketamine treatment in major depressive disorder: a systematic review and meta-analysis
Muhammad Youshay Jawad, Joshua D. Di Vincenzo, Felicia Ceban, Saja Jaberi, Leanna M.W. Lui, Emily S. Gillissie, Yazen Alnafeesi, Joshua D. Rosenblat, Roger S McIntyre
Expert Opinion on Drug Safety April 6, 2022 DOI: 10.1080/14740338.2022.2058488 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Randomized Peer reviewed |
|---|---|
| Population | Patients with treatment-resistant depression or depression with suicidal ideation and behavior |
| Intervention | Intranasal esketamine |
| Duration | At least 4 weeks, with year-long trials included |
| Topics | Depression Esketamine |
| Keywords | Depression economics Placebo Suicidal ideation Meta-analysis Adjunctive treatment Randomized controlled trial Anesthesia Poison control Injury prevention Emergency medicine |
| Citations | 29 |
| Key findings | Adjunctive intranasal esketamine was safe and more effective than intranasal placebo at reducing depressive symptoms, with higher response and remission rates and lower relapse rates over one year. |
Abstract
Introduction: Intranasal (IN) esketamine represents an innovative treatment for individuals with treatment resistant depression and depression with suicidal ideation and behavior. Herein, we synthesize extant long-term studies (≥ 4 weeks) regarding this treatment. RESEARCH DESIGN AND
Methods: The interventional studies of IN esketamine in patients with depression having a study period of at least four weeks were included for our synthesis. A meta-analysis was undertaken for the efficacy and safety parameters of adjunctive IN esketamine vs IN placebo with an oral antidepressant. The data excluded from meta-analysis were synthesized narratively.
Results: After pooling data from seven randomized controlled trials, treatment with adjunctive IN esketamine vs IN placebo was safe overall, and more effective at decreasing depressive symptoms (d = -0.239; 95%CI = -0.335,-0.142;p < 0.0001), with higher response (RR = 1.221; 95% CI = 1.055,1.428; p = 0.017) and remission (RR = 1.366; 95% CI = 1.182,1.578; p < 0.0001) rates. The year-long trials showed that treatment with adjunctive IN esketamine led to lower relapse rates with no considerable long-term side effects.
Conclusion: Intranasal esketamine was demonstrated to be safe, well tolerated, and rapidly effective in individuals with treatment resistant depression, suicidal ideation, and suicidal behavior.
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 |