February 2026
Ketamine
What February 2026's 25 new studies found, synthesized from the papers below. All Ketamine research →
The synthesis
Synthesized from 25 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 published in February 2026 consistently finds that ketamine and esketamine produce rapid, short-term antidepressant and anti-suicidal effects in treatment-resistant depression, with some evidence of efficacy in special populations (e.g., older adults with MCI, adolescents) and for PTSD. However, the evidence is limited by small sample sizes, open-label designs, and a lack of controlled comparisons with psychotherapy, and long-term durability remains unclear.
Confidence in the evidence
Moderate- Multiple reviews and RCTs (e.g., article_id 25087, 25155, 18898) consistently show rapid antidepressant effects, but many studies are narrative reviews or open-label trials.
- Sample sizes are often small (e.g., n=13 in 28831, n=67 in 28983) and few large-scale RCTs are reported.
- Evidence for adjunctive psychotherapy (KAP) is mixed, with controlled studies showing no significant difference from control (article_id 18884).
- Safety data from a systematic review (article_id 25166) suggest low rates of serious adverse events, but long-term risks (e.g., cystitis, cognitive effects) are not fully resolved.
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 |
|---|---|---|---|---|
| Ketamine and Esketamine Therapy in Affective Disorders: A Comprehensive Review of Mechanisms, Clinical Evidence, Safety, and Future Directions 2026 | review | Supports | IV ketamine and intranasal esketamine produce rapid antidepressant effects within hours in treatment-resistant patients, but require monitoring for dissociation, sedation, and misuse risk. | |
| Ketamine pharmacotherapy for major depressive disorder: A narrative review 2026 | narrative review | Mixed | IV and IN ketamine show mixed-to-positive antidepressant effects in a limited-to-moderate number of studies, with common adverse effects including dissociation, sedation, and hypertension. | |
| Adverse drug events and toxicological mechanisms of esketamine: a study based on US Food and Drug Administration Adverse Event Reporting System and network toxicology analysis. 2026 | observational | Unclear | This study analyzed adverse drug events and toxicological mechanisms of esketamine using FAERS data and network toxicology, but the abstract does not report specific findings. | |
| Using Classification and Regression Tree Modeling to Investigate the Effects of Subanesthetic Ketamine Infusion on Remission of Suicidal Symptoms. 2026 | post hoc analysis of RCT and open-label trials | 67 | Supports | Combinations of clinical predictors (mild/moderate depression, shorter episode, ≤4 failed antidepressants, low/moderate suicide risk, history of attempts) predicted rapid and sustained anti-suicidal effects of a single ketamine infusion. |
| KET-MCI: A Pilot Safety and Tolerability Study of Single Infusion Intravenous Ketamine for Older Adults with Depression and Mild Cognitive Impairment 2026 | open-label clinical trial | 13 | Supports | A single ketamine infusion was safe and well-tolerated, and associated with large-magnitude improvement in depression severity at 24 hours, with some benefit persisting up to 1 month. |
| Multiple peripheral inflammatory markers in adolescents with major depressive disorder treated with repeated esketamine infusions: results from a randomized controlled trial. 2026 | RCT | Unclear | This RCT examined multiple peripheral inflammatory markers in adolescents treated with repeated esketamine infusions, but the abstract does not report results. | |
| Integrating Psychiatric, Psychotherapeutic, and Nursing Care in Intranasal Esketamine for Treatment-Resistant Depression 2026 | narrative review | Supports | Intranasal esketamine provides rapid symptom relief in TRD, and the review proposes a phase-based multidisciplinary framework integrating psychiatry, nursing, and psychotherapy. | |
| The use of repetitive transcranial magnetic stimulation (rTMS), electroconvulsive therapy (ECT), ketamine, and esketamine in reducing suicidality in major depressive disorder: A comprehensive narrative review 2026 | narrative review | Supports | Ketamine and esketamine are associated with reductions in suicidal ideation in MDD, with the strongest RCT evidence supporting rapid, short-term effects. | |
| Ketamine as a Mental Health Treatment 2026 | review | Supports | Ketamine is a promising intervention for treatment-resistant depression, anxiety, and PTSD, but regulation remains fragmented and evidence is evolving. | |
| Sex differences in placebo and antidepressant response to intranasal esketamine for treatment-resistant depression 2026 | pooled analysis of RCTs | Mixed | Esketamine improved depression in both sexes, but females showed greater improvement and higher response rates toward the end of trials, while males showed earlier sadness reduction. | |
| Ketamine or Esketamine in Special Populations of Patients With Treatment-Resistant Depression 2026 | non-systematic review | Supports | Ketamine and esketamine show efficacy in multiple TRD subpopulations, with key challenges including psychotomimetic effects and cardiovascular adverse effects. | |
| The Antioxidant Activity of Ketamine: Threshold-Dependent Mechanism in Treatment-Resistant Depression? 2026 | preclinical | Supports | Ketamine at 25 ng/mL increased viability of neuronal cells under high oxidative stress, suggesting a threshold-dependent antioxidant mechanism relevant to TRD. | |
| The psychoactive effects of repeated ketamine infusions and their mechanistic role in the treatment of alcohol use disorder: Secondary analysis of a randomised controlled trial 2026 | secondary analysis of RCT | No effect | Ketamine's psychoactive effects were consistent across three infusions, but reductions in alcohol consumption were not mediated by these acute psychoactive effects. | |
| ADVERSE EFFECTS OF ESKETAMINE IN TREATMENT RESISTANT DEPRESSION: A COMPREHENSIVE LITERATURE REVIEW (2020-2025) 2026 | systematic review | Supports | Common adverse effects (dissociation, sedation) resolved within 2 hours; blood pressure elevations normalized within 1.5 hours; serious adverse events were infrequent (<0.2% of sessions). | |
| At-Home Ketamine-Assisted Therapy for Post-Traumatic Stress Disorder: A Real-World Retrospective Analysis 2026 | retrospective analysis | 374 | Supports | At-home ketamine-assisted therapy was associated with a 44.6% reduction in PTSD symptoms, with 79.7% response and 60.7% remission rates after 6 sessions. |
| Ketamine for depression 2026 | thesis (includes RCT and real-world data) | Mixed | Fixed low doses of oral esketamine were not effective, but higher individualized dosing led to meaningful improvement in a subgroup; ketamine was often effective and well-tolerated in complex cases. | |
| Ketamine attenuates habenula activity in response to aversive outcomes during Pavlovian learning 2026 | RCT | 70 | Supports | Ketamine attenuated habenula activity during aversive stimuli expectations and outcomes 24 hours post-infusion, providing translational support for preclinical models. |
| Narrative Experiences of Esketamine-Induced Dissociation in Patients with Treatment-Resistant Depression: A Qualitative Exploratory Study 2026 | qualitative exploratory study | 36 | Mixed | Most patients framed dissociation as neutral or meaningful, with four experiential domains identified; a minority reported transient distress or loss of control. |
| Effectiveness of ketamine-assisted psychotherapy as a treatment for treatment-resistant depression: a systematic review. 2026 | systematic review | Mixed | KAP was associated with reductions in depressive symptoms, with some improvements sustained up to six months, but controlled studies found no significant differences between KAP and control conditions. | |
| Factors for predicting response to electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) and ketamine in patients with treatment-resistant depression: a systematic review. 2026 | systematic review | Mixed | Predictors of response to ketamine (e.g., inflammation markers, fronto-limbic connectivity) show promise but are inconsistent across studies, limiting clinical use. | |
| Oxidative Stress in Treatment-Resistant and Refractory Depression: A Hidden Therapeutic Target? 2026 | review | Supports | Oxidative stress may be a biomarker of persistence and severity in TRD, and ketamine's antioxidant activity could be a therapeutic target. | |
| A Randomized Controlled Trial on the Efficacy of Ketamine vs. Electroconvulsive Therapy in Severe Depression with Suicidal Ideation. 2026 | RCT | 64 | Supports | Both ECT and ketamine significantly reduced depressive symptoms and suicidal ideation, with no significant difference between groups at 4-week follow-up. |
| Grayken lessons: a multidisciplinary approach to care for a patient with severe ketamine use disorder. 2026 | case report | 1 | Opposes | Chronic non-medical ketamine use led to severe ketamine use disorder, gastrointestinal toxicity, and ketamine-induced uropathy, highlighting risks of misuse. |
| Age-related moderation of adjunctive psychotherapy and early life stress effects on depression symptom reductions following ketamine treatment: Initial insights from a large, naturalistic sample. 2026 | observational | 224 | Mixed | Depression symptoms improved over time, but symptom trajectories did not differ between ketamine-assisted therapy and infusions alone; higher early life stress was associated with greater symptom reduction. |
| Neurotransmitter Mechanisms of Ketamine and Ketamine–Magnesium Sulfate-Induced Hypothermia: Evidence for Serotonergic and Adrenergic Involvement Without GABAA Contributions 2026 | preclinical | Unclear | Ketamine-induced hypothermia involves serotonergic and adrenergic (α2) mechanisms but not GABAA, with bidirectional effects of methysergide depending on dose. |
IV ketamine and intranasal esketamine produce rapid antidepressant effects within hours in treatment-resistant patients, but require monitoring for dissociation, sedation, and misuse risk.
review
IV and IN ketamine show mixed-to-positive antidepressant effects in a limited-to-moderate number of studies, with common adverse effects including dissociation, sedation, and hypertension.
narrative review
This study analyzed adverse drug events and toxicological mechanisms of esketamine using FAERS data and network toxicology, but the abstract does not report specific findings.
observational
Combinations of clinical predictors (mild/moderate depression, shorter episode, ≤4 failed antidepressants, low/moderate suicide risk, history of attempts) predicted rapid and sustained anti-suicidal effects of a single ketamine infusion.
post hoc analysis of RCT and open-label trials Sample size: 67
A single ketamine infusion was safe and well-tolerated, and associated with large-magnitude improvement in depression severity at 24 hours, with some benefit persisting up to 1 month.
open-label clinical trial Sample size: 13
This RCT examined multiple peripheral inflammatory markers in adolescents treated with repeated esketamine infusions, but the abstract does not report results.
RCT
Intranasal esketamine provides rapid symptom relief in TRD, and the review proposes a phase-based multidisciplinary framework integrating psychiatry, nursing, and psychotherapy.
narrative review
Ketamine and esketamine are associated with reductions in suicidal ideation in MDD, with the strongest RCT evidence supporting rapid, short-term effects.
narrative review
Ketamine is a promising intervention for treatment-resistant depression, anxiety, and PTSD, but regulation remains fragmented and evidence is evolving.
review
Esketamine improved depression in both sexes, but females showed greater improvement and higher response rates toward the end of trials, while males showed earlier sadness reduction.
pooled analysis of RCTs
Ketamine and esketamine show efficacy in multiple TRD subpopulations, with key challenges including psychotomimetic effects and cardiovascular adverse effects.
non-systematic review
Ketamine at 25 ng/mL increased viability of neuronal cells under high oxidative stress, suggesting a threshold-dependent antioxidant mechanism relevant to TRD.
preclinical
Ketamine's psychoactive effects were consistent across three infusions, but reductions in alcohol consumption were not mediated by these acute psychoactive effects.
secondary analysis of RCT
Common adverse effects (dissociation, sedation) resolved within 2 hours; blood pressure elevations normalized within 1.5 hours; serious adverse events were infrequent (<0.2% of sessions).
systematic review
At-home ketamine-assisted therapy was associated with a 44.6% reduction in PTSD symptoms, with 79.7% response and 60.7% remission rates after 6 sessions.
retrospective analysis Sample size: 374
Fixed low doses of oral esketamine were not effective, but higher individualized dosing led to meaningful improvement in a subgroup; ketamine was often effective and well-tolerated in complex cases.
thesis (includes RCT and real-world data)
Ketamine attenuated habenula activity during aversive stimuli expectations and outcomes 24 hours post-infusion, providing translational support for preclinical models.
RCT Sample size: 70
Most patients framed dissociation as neutral or meaningful, with four experiential domains identified; a minority reported transient distress or loss of control.
qualitative exploratory study Sample size: 36
KAP was associated with reductions in depressive symptoms, with some improvements sustained up to six months, but controlled studies found no significant differences between KAP and control conditions.
systematic review
Predictors of response to ketamine (e.g., inflammation markers, fronto-limbic connectivity) show promise but are inconsistent across studies, limiting clinical use.
systematic review
Oxidative stress may be a biomarker of persistence and severity in TRD, and ketamine's antioxidant activity could be a therapeutic target.
review
Both ECT and ketamine significantly reduced depressive symptoms and suicidal ideation, with no significant difference between groups at 4-week follow-up.
RCT Sample size: 64
Chronic non-medical ketamine use led to severe ketamine use disorder, gastrointestinal toxicity, and ketamine-induced uropathy, highlighting risks of misuse.
case report Sample size: 1
Depression symptoms improved over time, but symptom trajectories did not differ between ketamine-assisted therapy and infusions alone; higher early life stress was associated with greater symptom reduction.
observational Sample size: 224
Ketamine-induced hypothermia involves serotonergic and adrenergic (α2) mechanisms but not GABAA, with bidirectional effects of methysergide depending on dose.
preclinical
Points of agreement
- Ketamine and esketamine produce rapid antidepressant effects, often within hours, in treatment-resistant depression.
- Both agents are associated with reductions in suicidal ideation, with strongest evidence from RCTs for short-term effects.
- Common adverse effects (dissociation, sedation, hypertension) are transient and generally resolve within hours.
- Efficacy is supported across multiple populations, including older adults, adolescents, and those with comorbidities.
Conflicts
- Controlled studies of ketamine-assisted psychotherapy (KAP) found no significant difference from control conditions, while open-label studies show benefit.
- Sex differences in response: females showed greater overall improvement, but males had earlier sadness reduction with esketamine.
- Fixed low-dose oral esketamine was ineffective, but higher individualized dosing showed benefit in a subgroup.
Gaps
- Long-term durability of antidepressant and anti-suicidal effects beyond 4 weeks to 6 months is not well established.
- Large-scale, adequately controlled trials comparing ketamine with active comparators (e.g., ECT, rTMS) are lacking.
- Predictors of response (clinical, biological, imaging) remain inconsistent and not clinically validated.
- Safety of chronic or repeated use, including cognitive effects and urological toxicity, requires further study.
- Real-world implementation frameworks for multidisciplinary care are proposed but not empirically tested.