April 2026
Ketamine
What April 2026's 25 new studies found, synthesized from the papers below. All Ketamine research →
The synthesis
Synthesized from 13 studies in the library · AI-generated, grounded in the abstracts below
Found by searching the library for Ketamine, esketamine, arketamine, then ranked by relevance.
Research on ketamine in April 2026 continued to show rapid antidepressant effects, particularly for treatment-resistant depression, but with variable response and notable side effects. Evidence from multiple studies supports its efficacy, though durability of response and optimal dosing intervals remain key concerns. The main caveat is that most studies have short follow-up periods and small sample sizes, limiting generalizability.
Confidence in the evidence
Moderate- Multiple RCTs and systematic reviews consistently show rapid antidepressant effects of ketamine/esketamine in TRD.
- Sample sizes are generally small (e.g., n=18, n=14, n=34), and many studies are open-label or retrospective.
- Heterogeneity in dosing protocols and follow-up durations limits direct comparisons.
- Adverse events like dissociation and blood pressure elevation are consistently reported.
How we rate confidence
Confidence reflects the strength of the underlying evidence, not whether the result is favorable. It weighs the number and size of studies, their design (randomized trials count for more than observational or single-case work), how consistently they point the same way, and their risk of bias.
Tiers run from Insufficient to High. High is rare in this field: small, early, or open-label studies land lower even when their direction is encouraging.
Evidence by study
Direction is each study's finding relative to your question: Supports, Opposes, No effect, Mixed, or Unclear.
| Study | Design | Sample size | Direction | Finding |
|---|---|---|---|---|
| Effects of a Single Sub-Anesthetic Dose of Ketamine in Tobacco Use Disorder: An Active-Placebo, Randomized Crossover Study 2026 | RCT | 18 | No effect | A single sub-anesthetic dose of ketamine did not significantly reduce cigarette smoking, craving, or withdrawal compared to midazolam. |
| Pharmacological augmentation in treatment-resistant depression: a neurobiologically informed, practical decision guide for treatment choice with lithium, quetiapine, or esketamine. 2026 | narrative review | Supports | Esketamine is one of three augmentation strategies for TRD, with distinct clinical characteristics that may guide individualized treatment. | |
| Repeated intranasal esketamine augmentation in treatment-resistant obsessive-compulsive disorder with comorbid major depressive disorder: a prospective case series. 2026 | prospective case series | 8 | Mixed | Intranasal esketamine improved depressive symptoms substantially (48.8% reduction in MADRS) but showed more modest and heterogeneous effects on OCD symptoms (30.3% reduction in Y-BOCS). |
| The role of cytochrome P450 polymorphisms in the pharmacokinetics of oral esketamine. 2026 | observational | 18 | Supports | CYP2B6 516 G>T carriers had significantly higher esketamine plasma levels than non-carriers, suggesting a genetic influence on bioavailability. |
| Preliminary evidence that serum interleukin-6 is a candidate biomarker of response to esketamine in treatment-resistant depression. 2026 | open-label Phase 2 trial | 14 | Supports | Higher baseline serum IL-6 levels predicted more rapid symptom reduction with esketamine, while lower IL-6 predicted greater severity and disability. |
| Esketamine-sufentanil PCA reduces postoperative depression state in elderly colorectal cancer patients: a randomized controlled trial. 2026 | RCT | 99 | Supports | Low-dose esketamine (1 mg/kg) added to sufentanil PCA significantly reduced postoperative depression and anxiety without enhancing analgesia or increasing adverse events. |
| Ketamine Use in Critically Ill Patients: Insights into Depressive Symptoms and Hemodynamic Changes. 2026 | retrospective study | 34 | Supports | Subanesthetic ketamine infusions were associated with improvement in apparent and reported sadness, with stable hemodynamics. |
| Comparison of average time-to-relapse following ECT versus ketamine - A systematic review. 2026 | systematic review | Mixed | Both ECT and ketamine show sustained therapeutic potential, but ECT may be associated with longer remission; increased dose/frequency and maintenance treatment prolong remission. | |
| Ketamine and Esketamine in Obsessive-Compulsive Disorder: A Scoping Review of Clinical and Mechanistic Evidence. 2026 | scoping review | Mixed | Ketamine can produce rapid reductions in obsessive symptoms, but results are inconsistent; most trials evaluated single administrations. | |
| A systematic review of ketamine and esketamine-induced long-term potentiation and synaptic scaling: Do the molecular and synaptic plasticity effects inform dosing intervals? 2026 | systematic review | Supports | A single 0.5 mg/kg IV ketamine infusion produces rapid but transient antidepressant effects peaking at 24 hours and declining over 2-3 days; twice-weekly dosing may be sufficient. | |
| Comparison of rTMS and esketamine for treatment-resistant depression: A target trial emulation. 2026 | cohort study (target trial emulation) | 3380 | Mixed | rTMS was associated with a lower risk of hospitalization and arrhythmia than esketamine, but esketamine showed a protective association against suicide in older patients. |
| A Systematic Review and Meta-Analysis of the Efficacy and Safety of Intranasal Esketamine for Rapid Symptom Relief in Treatment-resistant Depression. 2026 | systematic review and meta-analysis | Supports | Intranasal esketamine plus an antidepressant produced significant improvement in MADRS scores within 24 hours, but with higher incidence of adverse events like elevated blood pressure and dissociation. | |
| Sustained effectiveness and safety of esketamine for major depressive disorder: a target trial simulation of real-world data. 2026 | target trial simulation | Supports | Real-world data simulation supports sustained effectiveness and safety of esketamine for MDD. |
A single sub-anesthetic dose of ketamine did not significantly reduce cigarette smoking, craving, or withdrawal compared to midazolam.
RCT Sample size: 18
Esketamine is one of three augmentation strategies for TRD, with distinct clinical characteristics that may guide individualized treatment.
narrative review
Intranasal esketamine improved depressive symptoms substantially (48.8% reduction in MADRS) but showed more modest and heterogeneous effects on OCD symptoms (30.3% reduction in Y-BOCS).
prospective case series Sample size: 8
CYP2B6 516 G>T carriers had significantly higher esketamine plasma levels than non-carriers, suggesting a genetic influence on bioavailability.
observational Sample size: 18
Higher baseline serum IL-6 levels predicted more rapid symptom reduction with esketamine, while lower IL-6 predicted greater severity and disability.
open-label Phase 2 trial Sample size: 14
Low-dose esketamine (1 mg/kg) added to sufentanil PCA significantly reduced postoperative depression and anxiety without enhancing analgesia or increasing adverse events.
RCT Sample size: 99
Subanesthetic ketamine infusions were associated with improvement in apparent and reported sadness, with stable hemodynamics.
retrospective study Sample size: 34
Both ECT and ketamine show sustained therapeutic potential, but ECT may be associated with longer remission; increased dose/frequency and maintenance treatment prolong remission.
systematic review
Ketamine can produce rapid reductions in obsessive symptoms, but results are inconsistent; most trials evaluated single administrations.
scoping review
A single 0.5 mg/kg IV ketamine infusion produces rapid but transient antidepressant effects peaking at 24 hours and declining over 2-3 days; twice-weekly dosing may be sufficient.
systematic review
rTMS was associated with a lower risk of hospitalization and arrhythmia than esketamine, but esketamine showed a protective association against suicide in older patients.
cohort study (target trial emulation) Sample size: 3380
Intranasal esketamine plus an antidepressant produced significant improvement in MADRS scores within 24 hours, but with higher incidence of adverse events like elevated blood pressure and dissociation.
systematic review and meta-analysis
Real-world data simulation supports sustained effectiveness and safety of esketamine for MDD.
target trial simulation
Points of agreement
- Ketamine and esketamine produce rapid antidepressant effects in treatment-resistant depression.
- Response is often transient, peaking around 24 hours and declining within days.
- Adverse events such as dissociation and blood pressure elevation are consistently reported.
- Biomarkers like IL-6 and CYP2B6 genotype may predict response or pharmacokinetics.
Conflicts
- Some studies show significant antidepressant effects, while others (e.g., in tobacco use disorder) find no benefit.
- Evidence for OCD is mixed: some studies show improvement, others inconsistent results.
- Comparative effectiveness with ECT or rTMS is unclear; one study suggests ECT may yield longer remission, another shows rTMS has better safety profile.
Gaps
- Long-term durability of response and optimal maintenance dosing are not well established.
- Most studies have small sample sizes and short follow-up periods.
- Real-world tolerability and safety beyond clinical trials are insufficiently explored.
- Predictive biomarkers for differential response are lacking.
- Data on ketamine/esketamine in special populations (e.g., ICU, elderly, comorbid conditions) are limited.