THE IMPACT OF INTRANASAL ESKETAMINE ON TREATMENT-RESISTANT DEPRESSION: A SYSTEMATIC REVIEW
Wojciech Kotlarski, Klaudia Magdalena Kotlarska, Tomasz Stanisław Mainka, Emil Sergejuk
International Journal of Innovative Technologies in Social Science June 25, 2026 DOI: 10.31435/ijitss.2(50).2026.5523 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Qualitative Peer reviewed |
|---|---|
| Population | Adults with treatment-resistant depression |
| Intervention | Intranasal esketamine |
| Topics | Depression Ketamine Esketamine |
| Keywords | Adverse effect Nasal administration Systematic review Randomized controlled trial Depression economics Clinical trial Meta-analysis Nausea Medline Tolerability Anesthesia |
| Key findings | Intranasal esketamine is associated with greater symptom improvement and higher response rates than control in TRD, but with more frequent adverse events such as dizziness and nausea. |
Abstract
Introduction: Treatment-resistant depression (TRD) is a major public health and societal challenge, associated with persistent symptoms, functional impairment, and increased healthcare and economic burden. Intranasal esketamine has emerged as a rapid-acting adjunctive therapy with a distinct glutamatergic mechanism of action. This systematic review summarizes current evidence on its effectiveness and implementation-relevant outcomes in TRD.
Methods: A systematic literature review was conducted in accordance with PRISMA 2020. PubMed/MEDLINE and EMBASE were searched for English-language systematic reviews and meta-analyses published between 2010 and 2026 using database-specific but equivalent Boolean strategies combining intranasal esketamine terms with TRD terms. Titles/abstracts were screened and eligible records underwent full-text assessment. Five studies were included in qualitative synthesis. The last search was conducted on 5 March 2026.
Results: Meta-analytic evidence from randomized trials reported greater symptom improvement with intranasal esketamine versus control (MADRS SMD = −3.88; 95% CI −5.71 to −2.05) and higher response rates (RR = 1.99; 95% CI 1.28–3.10), alongside improvements in disability (SDS SMD = −3.01) and patient-reported symptoms (PHQ-9 SMD = −2.32). Adverse events were more frequent, including dizziness (RR = 3.55) and nausea (RR = 3.88). Real-world data showed substantial symptom reduction (Hedges’ g = −1.98) and higher remission likelihood at three months (OR = 5.1), with high overall adverse-event prevalence (82%) and dissociation commonly reported (49%).
Conclusions: Intranasal esketamine shows clinically relevant benefits in TRD with convergent trial and real-world signals, but requires supervised delivery and sustained follow-up. Further research should clarify long-term outcomes, clinical meaningfulness, and health-system cost-effectiveness.