February 2026
Depression
What February 2026's 25 new studies found, synthesized from the papers below. All Depression research →
The synthesis
Synthesized from 25 studies in the library · AI-generated, grounded in the abstracts below
Found by searching the library for Depression, major depressive disorder, MDD, depressive disorder, treatment-resistant depression, then ranked by relevance.
Research in February 2026 found that ketamine and esketamine produce rapid, short-term antidepressant effects in treatment-resistant depression, with some evidence supporting psilocybin and DMT as promising interventions. Results are generally consistent across studies, but most evidence comes from open-label or small trials, and durability of effects beyond a few months remains unclear.
Confidence in the evidence
Moderate- Multiple reviews and RCTs support ketamine/esketamine efficacy, but many studies are open-label or small.
- Psilocybin and DMT show positive signals, but evidence is from phase 2 trials or naturalistic designs.
- Consistent direction across studies, but sample sizes are often limited and blinding is challenging.
- Few large-scale, long-term RCTs exist; most evidence is short-term.
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 | Ketamine and esketamine produce rapid antidepressant effects within hours in treatment-resistant depression. | |
| Ketamine pharmacotherapy for major depressive disorder: A narrative review 2026 | narrative review | Mixed | IV and IN ketamine show mixed-to-positive antidepressant effects in limited-to-moderate samples. | |
| A phase 2 uncontrolled, open-label study of intranasal BPL-003 (5-methoxy- N,N -dimethyltryptamine) in patients with treatment-resistant depression 2026 | open-label study | Supports | Intranasal BPL-003 (5-MeO-DMT) showed rapid and sustained MADRS reduction over 12 weeks. | |
| Psilocybin for psychiatric disorders: History, clinical trials, neuroimaging, and regulations 2026 | review | Supports | Psilocybin shows therapeutic effects in MDD and depressive symptoms in life-threatening illnesses. | |
| Predictors of the Effectiveness of Psychedelics in Treating Depression—A Scoping Review 2026 | scoping review | 48 | Supports | Process-level features during dosing (emotional breakthrough, mystical experiences) are the most consistent correlates of antidepressant improvement. |
| 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 | Single ketamine infusion was safe and associated with large-magnitude improvement in depression at 24 hours and up to 1 month. |
| Safety and Efficacy of Microdosing Psilocybin over 8 Weeks for Major Depressive Disorder: A Randomized Clinical Trial 2026 | RCT | 39 | No effect | Microdosing psilocybin (2 mg) did not outperform placebo on PHQ-9 reduction at 4 weeks. |
| Multiple peripheral inflammatory markers in adolescents with major depressive disorder treated with repeated esketamine infusions: results from a randomized controlled trial. 2026 | RCT | Unclear | Study examined peripheral inflammatory markers after repeated esketamine infusions; direction not specified in abstract. | |
| 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, but real-world implementation requires multidisciplinary integration. | |
| Ketamine as a Mental Health Treatment 2026 | review | Supports | Ketamine is a promising intervention for treatment-resistant depression, anxiety, and PTSD. | |
| 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 rapid, short-term reductions in suicidal ideation in MDD. | |
| Mental health outcomes following a psilocybin session within Oregon’s state-regulated model: A naturalistic study 2026 | naturalistic study | 88 | Supports | Depression, anxiety, and well-being improved significantly 30 days after a psilocybin session. |
| LSD microdosing for major depressive disorder: Mood and pharmacokinetic outcomes from a Phase 2a trial 2026 | phase 2a trial | Supports | Microdosed LSD showed short-term mood improvements in depression, warranting controlled trials. | |
| 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 overall improvement and higher response odds than males. | |
| Ketamine or Esketamine in Special Populations of Patients With Treatment-Resistant Depression 2026 | non-systematic review | Supports | Ketamine and esketamine show promise as effective and relatively safe treatments in selected sensitive subgroups of TRD. | |
| The Antioxidant Activity of Ketamine: Threshold-Dependent Mechanism in Treatment-Resistant Depression? 2026 | preclinical study | Supports | Ketamine showed a protective antioxidant effect on neuronal cells only at high oxidative stress levels typical of TRD. | |
| A short-acting psychedelic intervention for major depressive disorder: a phase IIa randomized placebo-controlled trial. 2026 | RCT | 34 | Supports | Single DMT infusion produced significantly greater MADRS reduction than placebo at 2 weeks, with effects persisting up to 3 months. |
| Microdosing psilocybin for major depressive disorder: study protocol for a phase II double-blind placebo-controlled randomised partial crossover trial 2026 | study protocol | 40 | Unclear | Protocol for a phase II RCT of microdosing psilocybin for MDD; results not yet published. |
| ADVERSE EFFECTS OF ESKETAMINE IN TREATMENT RESISTANT DEPRESSION: A COMPREHENSIVE LITERATURE REVIEW (2020-2025) 2026 | systematic review | Supports | Esketamine adverse effects (dissociation, sedation, BP elevation) are transient; serious events are rare (<0.2% of sessions). | |
| Low-income group psilocybin assisted therapy for depression: An Oregon feasibility study 2026 | open-label feasibility study | 20 | Supports | Group psilocybin therapy was feasible and associated with significant reduction in Hamilton Depression scores (Cohen's d = 1.89). |
| Time-Dependent Effects of Rapid-Acting Antidepressants in iPSC-Derived Neurons from Treatment-Resistant Depression and Healthy Volunteers. 2026 | preclinical study | Supports | Ketamine and psychedelics share convergent transcriptomic effects on inflammation, mTORC1, and synaptic pathways in human neurons. | |
| Examining the effects of psilocybin-assisted psychotherapy on anhedonia in treatment-resistant depression 2026 | secondary analysis of RCT | 30 | Supports | Psilocybin-assisted psychotherapy significantly reduced anhedonia at 2 weeks, with improvements lasting up to 6 months. |
| 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 and 60.7% remission rate. |
| Ketamine for depression 2026 | thesis (includes RCT and observational data) | Mixed | Fixed low doses of oral esketamine were not effective, but higher individualized dosing led to meaningful improvement in a subgroup. | |
| MDMA-assisted therapy as a treatment for major depressive disorder: proof of principle study - CORRIGENDUM. 2026 | corrigendum | Unclear | No abstract available; corrigendum for a proof-of-principle study on MDMA-assisted therapy for MDD. |
Ketamine and esketamine produce rapid antidepressant effects within hours in treatment-resistant depression.
review
IV and IN ketamine show mixed-to-positive antidepressant effects in limited-to-moderate samples.
narrative review
Intranasal BPL-003 (5-MeO-DMT) showed rapid and sustained MADRS reduction over 12 weeks.
open-label study
Psilocybin shows therapeutic effects in MDD and depressive symptoms in life-threatening illnesses.
review
Process-level features during dosing (emotional breakthrough, mystical experiences) are the most consistent correlates of antidepressant improvement.
scoping review Sample size: 48
Single ketamine infusion was safe and associated with large-magnitude improvement in depression at 24 hours and up to 1 month.
open-label clinical trial Sample size: 13
Microdosing psilocybin (2 mg) did not outperform placebo on PHQ-9 reduction at 4 weeks.
RCT Sample size: 39
Study examined peripheral inflammatory markers after repeated esketamine infusions; direction not specified in abstract.
RCT
Intranasal esketamine provides rapid symptom relief in TRD, but real-world implementation requires multidisciplinary integration.
narrative review
Ketamine is a promising intervention for treatment-resistant depression, anxiety, and PTSD.
review
Ketamine and esketamine are associated with rapid, short-term reductions in suicidal ideation in MDD.
narrative review
Depression, anxiety, and well-being improved significantly 30 days after a psilocybin session.
naturalistic study Sample size: 88
Microdosed LSD showed short-term mood improvements in depression, warranting controlled trials.
phase 2a trial
Esketamine improved depression in both sexes, but females showed greater overall improvement and higher response odds than males.
pooled analysis of RCTs
Ketamine and esketamine show promise as effective and relatively safe treatments in selected sensitive subgroups of TRD.
non-systematic review
Ketamine showed a protective antioxidant effect on neuronal cells only at high oxidative stress levels typical of TRD.
preclinical study
Single DMT infusion produced significantly greater MADRS reduction than placebo at 2 weeks, with effects persisting up to 3 months.
RCT Sample size: 34
Protocol for a phase II RCT of microdosing psilocybin for MDD; results not yet published.
study protocol Sample size: 40
Esketamine adverse effects (dissociation, sedation, BP elevation) are transient; serious events are rare (<0.2% of sessions).
systematic review
Group psilocybin therapy was feasible and associated with significant reduction in Hamilton Depression scores (Cohen's d = 1.89).
open-label feasibility study Sample size: 20
Ketamine and psychedelics share convergent transcriptomic effects on inflammation, mTORC1, and synaptic pathways in human neurons.
preclinical study
Psilocybin-assisted psychotherapy significantly reduced anhedonia at 2 weeks, with improvements lasting up to 6 months.
secondary analysis of RCT Sample size: 30
At-home ketamine-assisted therapy was associated with a 44.6% reduction in PTSD symptoms and 60.7% remission rate.
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.
thesis (includes RCT and observational data)
No abstract available; corrigendum for a proof-of-principle study on MDMA-assisted therapy for MDD.
corrigendum
Points of agreement
- Ketamine and esketamine produce rapid antidepressant effects in treatment-resistant depression.
- Psilocybin and DMT show promise for depression, with effects lasting weeks to months.
- Adverse effects of ketamine/esketamine are generally transient and manageable.
- Process-level features (e.g., mystical experiences) are associated with better outcomes in psychedelic therapy.
Conflicts
- Microdosing psilocybin (2 mg) did not outperform placebo in one RCT, while other studies of psychedelic doses show positive effects.
- Fixed low-dose oral esketamine was ineffective, but higher individualized dosing showed benefit in a subgroup.
- Sex differences in response to esketamine: females showed greater overall improvement, but males had earlier sadness reduction.
Gaps
- Durability of antidepressant effects beyond 3-6 months is not well studied.
- Most studies are small, open-label, or lack active placebo controls.
- Long-term safety data for psychedelics and ketamine are limited.
- Predictors of response (e.g., biomarkers, patient characteristics) are not yet validated.
- Real-world implementation and access (e.g., cost, multidisciplinary care) remain understudied.