July 2026
Esketamine
What July 2026's 19 new studies found, synthesized from the papers below. All Esketamine research →
The synthesis
Synthesized from 19 studies in the library · AI-generated, grounded in the abstracts below
Found by searching the library for Esketamine, S-ketamine, spravato, esketamine nasal spray, then ranked by relevance.
Research published in July 2026 indicates that esketamine, particularly intranasal, is effective for treatment-resistant depression, with meta-analytic evidence showing modest acute improvement and reduced relapse risk, though it increases adverse events like dissociation and elevated blood pressure. Real-world studies confirm meaningful reductions in depressive symptoms, with comparable effectiveness to IV or IM ketamine, and some evidence of an anti-suicidal effect independent of mood improvement. However, the evidence base remains limited by heterogeneity, small sample sizes, and a lack of long-term durability data, and findings on biomarkers like BDNF are null.
Evidence by study
Direction is which way each study's own result points, not our rating of the study.
What the directions mean
- Supports:
- the study found the intervention worked, or its hypothesis held.
- Opposes:
- it found the opposite, no benefit or a harm.
- No effect:
- no significant difference either way.
- Mixed:
- effects in both directions within the same study.
- Unclear:
- the abstract does not report a direction.
| Study | Design | Sample size | Direction | Finding |
|---|---|---|---|---|
| (Es)ketamine in functional neurological disorder: a systematic review 2026 | systematic review | Unclear | The evidence base is insufficient to establish efficacy of (es)ketamine for functional neurological disorder, though some patients improved in functional symptoms. | |
| Esketamine's Therapeutic Effect on Anhedonia: A Post-hoc of a Randomized Controlled Trial 2026 | randomized controlled trial, post-hoc analysis | Supports | Esketamine reduced anhedonia symptoms compared to placebo in patients with treatment-resistant depression. | |
| Beyond Monoamines: Ketamine, Esketamine, and Classic Psychedelics in the Treatment of Depression 2026 | review | Supports | Argues that ketamine and esketamine have the strongest evidence among rapid-acting antidepressants for treatment-resistant depression, while psilocybin remains investigational. | |
| Clinical guidance on the use of esketamine nasal spray for patients with treatment resistant depression: A European Delphi consensus report. 2026 | modified Delphi panel | 30 | Supports | Expert consensus supported continuing esketamine nasal spray even with modest acute improvement and advocated for dose/frequency maximization to enhance outcomes. |
| Serum brain-derived neurotrophic factor following oral esketamine in treatment-resistant depression: Results from a randomized placebo-controlled trial. 2026 | randomized controlled trial | 54 | No effect | Repeated low-dose oral esketamine did not increase serum BDNF relative to placebo, and BDNF changes did not correlate with depression severity changes. |
| Is the reduction in suicidal ideation and deliberate self-harm during intranasal esketamine treatment independent of antidepressant response? A secondary, longitudinal analysis of a real-world TRD cohort with and without comorbid borderline personality disorder 2026 | secondary analysis of a longitudinal cohort | Supports | The within-person reduction in suicidal ideation over six months remained significant after adjusting for depressive severity, indicating an anti-suicidal effect partly independent of mood improvement. | |
| S-ketamine, but not R-ketamine, transiently suppresses front-loaded binge-like alcohol self-administration in male rats 2026 | experimental animal study | Supports | S-ketamine dose-dependently suppressed binge-like alcohol self-administration in male rats, but tolerance developed rapidly; R-ketamine had no effect. | |
| Real-world outcomes of intranasal esketamine and intravenous ketamine induction therapy for treatment-resistant depression in a community clinic: a retrospective cohort study 2026 | retrospective cohort study | 63 | Supports | Both intranasal esketamine and IV ketamine produced large reductions in depression severity during induction, with no significant between-group differences. |
| Esketamine for treatment-resistant depression: Comparing two maintenance schedules in an observational real-world study 2026 | retrospective observational cohort | 65 | Mixed | Esketamine was associated with significant reductions in depressive symptoms during induction, but no significant differences were found between front-loaded and spaced maintenance schedules. |
| Intranasal esketamine plus oral antidepressant for treatment-resistant depression: acute induction and maintenance relapse-prevention outcomes in a systematic review and meta-analysis 2026 | systematic review and meta-analysis | 1836 | Supports | Intranasal esketamine plus an oral antidepressant provided rapid, modest acute improvement and reduced relapse risk during maintenance, but increased acute adverse events such as dissociation and elevated blood pressure. |
| Real‐World Effectiveness and Cost‐Differential of Intranasal Esketamine Versus Intramuscular Ketamine 2026 | retrospective observational sequential cohort | 179 | Supports | IM ketamine was non-inferior to IN esketamine for depression and PTSD symptoms, with comparable safety and significantly lower cost per treatment course. |
| Psychedelics as a potential treatment for borderline personality disorder: A narrative review. 2026 | narrative review | Mixed | Preliminary evidence suggests ketamine, esketamine, and psilocybin may be safe and effective for improving core BPD symptoms and functioning, but high-quality research is needed. | |
| N,N-dimethyltryptamine elicits antidepressant and anxiolytic effects in helpless mice: a comparative study with S-ketamine. 2026 | animal study | Supports | DMT was as effective as S-ketamine in producing rapid and long-lasting antidepressant effects in helpless mice, and also showed anxiolytic-like effects. | |
| Case Report: Intranasal esketamine and accelerated intermittent theta-burst stimulation for severe treatment-resistant depression with suicidal ideation 2026 | case study | 1 | Supports | Combining intranasal esketamine with accelerated iTBS was feasible and associated with reduced depressive symptoms and suicidal ideation in a single patient. |
| Effect of intraoperative esketamine on moderate-to-severe depressive symptoms in major surgery patients: A randomized clinical trial. 2026 | randomized controlled trial | 435 | Supports | Intraoperative esketamine produced a significantly higher remission rate of depressive symptoms three days after major surgery compared with placebo (28.3% vs. 11.3%). |
| Targeting TLR4/PPARα-mediated neuroinflammation in the prefrontal cortex: S-ketamine and S-HNK rapidly alleviate depression-like behaviors 2026 | preclinical animal study | Supports | S-ketamine and S-hydroxynorketamine reversed depression-like behaviors, restored monoamine levels, and reduced neuroinflammation in mice by modulating the TLR4/PPARα signaling pathway. | |
| Clinical Predictors of Antidepressant Effects of Ketamine and Esketamine in Treatment-Resistant Unipolar and Bipolar Depression: A Systematic Review 2026 | systematic review | 12674 | Mixed | Most demographic and clinical variables did not predict differential antidepressant outcomes to ketamine or esketamine, though early response and family history of substance use disorders were promising predictors. |
| Dissociation and Antidepressant Response to Subcutaneous Esketamine: A Clinical Study 2026 | secondary exploratory analysis | 23 | Supports | Responders exhibited significantly higher CADSS total and derealization scores compared with non-responders across the treatment period. |
| QUALITY OF LIFE AND PRODUCTIVITY AMONG ESKETAMINE RESPONDERS IN A REAL-WORLD STUDY IN AUSTRALIA AND NEW ZEALAND 2026 | post-hoc subgroup analysis of an Early Access Program | 84 | Supports | Among esketamine responders, improvements in depression symptoms, quality of life, and work productivity were observed over 16 weeks. |
The evidence base is insufficient to establish efficacy of (es)ketamine for functional neurological disorder, though some patients improved in functional symptoms.
systematic review
Esketamine reduced anhedonia symptoms compared to placebo in patients with treatment-resistant depression.
randomized controlled trial, post-hoc analysis
Argues that ketamine and esketamine have the strongest evidence among rapid-acting antidepressants for treatment-resistant depression, while psilocybin remains investigational.
review
Expert consensus supported continuing esketamine nasal spray even with modest acute improvement and advocated for dose/frequency maximization to enhance outcomes.
modified Delphi panel Sample size: 30
Repeated low-dose oral esketamine did not increase serum BDNF relative to placebo, and BDNF changes did not correlate with depression severity changes.
randomized controlled trial Sample size: 54
The within-person reduction in suicidal ideation over six months remained significant after adjusting for depressive severity, indicating an anti-suicidal effect partly independent of mood improvement.
secondary analysis of a longitudinal cohort
S-ketamine dose-dependently suppressed binge-like alcohol self-administration in male rats, but tolerance developed rapidly; R-ketamine had no effect.
experimental animal study
Both intranasal esketamine and IV ketamine produced large reductions in depression severity during induction, with no significant between-group differences.
retrospective cohort study Sample size: 63
Esketamine was associated with significant reductions in depressive symptoms during induction, but no significant differences were found between front-loaded and spaced maintenance schedules.
retrospective observational cohort Sample size: 65
Intranasal esketamine plus an oral antidepressant provided rapid, modest acute improvement and reduced relapse risk during maintenance, but increased acute adverse events such as dissociation and elevated blood pressure.
systematic review and meta-analysis Sample size: 1836
IM ketamine was non-inferior to IN esketamine for depression and PTSD symptoms, with comparable safety and significantly lower cost per treatment course.
retrospective observational sequential cohort Sample size: 179
Preliminary evidence suggests ketamine, esketamine, and psilocybin may be safe and effective for improving core BPD symptoms and functioning, but high-quality research is needed.
narrative review
DMT was as effective as S-ketamine in producing rapid and long-lasting antidepressant effects in helpless mice, and also showed anxiolytic-like effects.
animal study
Combining intranasal esketamine with accelerated iTBS was feasible and associated with reduced depressive symptoms and suicidal ideation in a single patient.
case study Sample size: 1
Intraoperative esketamine produced a significantly higher remission rate of depressive symptoms three days after major surgery compared with placebo (28.3% vs. 11.3%).
randomized controlled trial Sample size: 435
S-ketamine and S-hydroxynorketamine reversed depression-like behaviors, restored monoamine levels, and reduced neuroinflammation in mice by modulating the TLR4/PPARα signaling pathway.
preclinical animal study
Most demographic and clinical variables did not predict differential antidepressant outcomes to ketamine or esketamine, though early response and family history of substance use disorders were promising predictors.
systematic review Sample size: 12674
Responders exhibited significantly higher CADSS total and derealization scores compared with non-responders across the treatment period.
secondary exploratory analysis Sample size: 23
Among esketamine responders, improvements in depression symptoms, quality of life, and work productivity were observed over 16 weeks.
post-hoc subgroup analysis of an Early Access Program Sample size: 84
Points of agreement
- Esketamine is effective for treatment-resistant depression, with consistent evidence of acute improvement and relapse prevention.
- Real-world studies show meaningful reductions in depressive symptoms with esketamine, comparable to IV or IM ketamine.
- Esketamine has an anti-suicidal effect that appears partly independent of its antidepressant effect.
- Adverse events, particularly dissociation and elevated blood pressure, are increased with esketamine.
Conflicts
- One study found no significant difference between esketamine and placebo on the primary outcome (oral esketamine), while most other studies found positive effects.
- Findings on the relationship between dissociation and antidepressant response are mixed: one study found responders had higher dissociation, while another found no significant correlation.
- Maintenance scheduling studies show no difference between front-loaded and spaced schedules, but expert consensus advocates for dose/frequency maximization.
Gaps
- Long-term durability of esketamine's antidepressant and anti-suicidal effects remains unclear.
- Most studies are uncontrolled or small, limiting generalizability.
- Optimal dosing and maintenance schedules are not well-established.
- Evidence for esketamine in special populations (e.g., BPD, perioperative) is preliminary.
- Biomarker research (e.g., BDNF) is inconclusive.
- Comparative effectiveness of esketamine versus other ketamine formulations (IV, IM) needs more rigorous study.