Brain Sciences
April 30, 2026
Nathan R Luzum, Marcia H. Mccall, Charlotte Talley Boyd et al.
A single sub-anesthetic dose of ketamine, compared to midazolam, produced a non-significant reduction in the number of cigarettes smoked during a requested abstinence period among 18 adults with tobacco use disorder who were not trying to quit. No significant differences appeared in ad-lib smoking, craving, or withdrawal symptoms afterward. Participants reported more intense psychological experiences with ketamine, and about half felt it was easier to abstain. The findings suggest ketamine has little to no direct effect on quantitative smoking measures, though qualitative reports indicate improved mood and reduced craving in some individuals for several days.
International journal of psychiatry in clinical practice
April 29, 2026
David Eckert, Siegfried Kasper
A narrative review presents a decision-making framework for three pharmacological augmentation strategies for treatment-resistant depression: lithium, quetiapine, and esketamine. The agents differ in pharmacological profile, monitoring requirements, and clinical application, though their mechanisms appear to converge on neuroplasticity pathways. Treatment selection may be guided by psychiatric presentation, somatic comorbidity, and practical feasibility. Validated predictive markers for differential response are currently lacking.
BMC psychiatry
April 26, 2026
Sergi López-rodríguez, Cinto Segalàs, Eva Real et al.
In eight adults with treatment-resistant obsessive-compulsive disorder and comorbid major depressive disorder, twelve weeks of intranasal esketamine (56-84 mg per session) substantially improved depressive symptoms, with MADRS scores decreasing by 48.8%. Obsessive-compulsive symptoms showed a more modest and heterogeneous reduction, with Y-BOCS scores decreasing by 30.3%. Half of participants achieved depression response, and half met OCD response criteria. Depressive symptoms improved earlier, while OCD symptoms followed a slower and more variable trajectory. These preliminary findings suggest that repeated intranasal esketamine may offer a therapeutic window for this severe subgroup, supporting further controlled studies.
The pharmacogenomics journal
April 24, 2026
Daniël T Coerts, Sanne Y Smith-Apeldoorn, Jérôme C Oude Nijhuis et al.
A genetic variation in the CYP2B6 enzyme, known as 516 G > T, is linked to higher blood levels of oral esketamine four hours after dosing in people with treatment-resistant depression. In a small sample of 18 participants from a placebo-controlled trial, carriers of the variant had median esketamine levels of 5.1 µg/L, compared to 2.1 µg/L in non-carriers. No significant associations were found for two other genetic variants, CYP3A4*22 and CYP3A5*3, but the numbers of carriers were very small. Larger studies are needed to clarify their effects.
Journal of psychopharmacology (Oxford, England)
April 24, 2026
Marco Colizzi, Elisa Morandin, Veronica Croccia et al.
In adults with treatment-resistant depression, higher baseline levels of the inflammatory marker interleukin-6 (IL-6) were associated with more rapid symptom reduction after intranasal esketamine treatment, while lower IL-6 predicted greater symptom severity and higher disability. IL-6 levels themselves did not change over the 24-week open-label phase 2 trial. The finding suggests that inflammation may play a role in treatment resistance and that baseline IL-6 could help guide personalized treatment decisions.
Scientific reports
April 21, 2026
Rong Ding, Daojie Wang, Guoxin Wang et al.
Adding low-dose esketamine (1 mg/kg) to sufentanil patient-controlled analgesia (PCA) significantly reduces postoperative depression and anxiety in elderly colorectal cancer patients without improving pain control or increasing side effects. In a double-blind trial of 99 patients aged 65 and older, those receiving esketamine had lower anxiety and depression scores at 24 and 72 hours after surgery compared to those given only sufentanil; no dose-dependent difference was seen between 1 mg/kg and 2 mg/kg esketamine. Pain scores and need for rescue analgesia did not differ between groups. Patient satisfaction was higher with esketamine (77% and 90%) than with sufentanil alone (50%). Adverse events were similar across groups.
Pharmaceuticals (Basel, Switzerland)
April 16, 2026
Maria Marmureanu, Mariana Valy Besoiu, Vlad Dionisie et al.
A substantial proportion of patients with obsessive-compulsive disorder (OCD) do not respond to first-line treatments. Ketamine and esketamine, NMDA receptor antagonists with rapid antidepressant effects, have attracted interest as potential treatments. This scoping review of 21 studies (5 preclinical, 16 clinical) found that preclinical evidence suggests ketamine and esketamine improve compulsive-like behaviors. Clinical studies suggest ketamine can produce rapid reductions in obsessive symptoms, though results remain inconsistent. Most trials evaluated single administrations; limited evidence suggests repeated dosing may provide greater benefit. The evidence remains preliminary and heterogeneous, and future research should prioritize adequately powered randomized trials with repeated dosing and longer follow-up.
Journal of intensive care medicine
April 16, 2026
Vrutti Patel, Saurabh Sujanyal, Lekhya Raavi et al.
Subanesthetic doses of ketamine improved specific depressive symptoms in critically ill intensive care unit patients without causing significant hemodynamic instability. In a retrospective study of 34 adults, including 18 solid organ transplant recipients, ketamine infusions (0.3-0.75 mg/kg over 40 minutes on three consecutive days) were associated with improvement in apparent sadness (90.0% vs 52.2%) and reported sadness (95.0% vs 59.1%). Among transplant recipients, improvement in apparent sadness remained significant (80.0% vs 41.7%). Heart rate increased transiently at 15-30 minutes post-infusion but returned to baseline by 60-90 minutes. Adverse effects included anxiety (12.5%), restlessness or agitation (10.4%), and dissociation (8.16%). These findings support ketamine's potential as a rapid-acting antidepressant in the ICU.
Journal of psychopharmacology (Oxford, England)
April 16, 2026
Minna Chang, Allan H Young, Mario F Juruena
Both electroconvulsive therapy (ECT) and ketamine show sustained therapeutic potential for treatment-resistant depression, with ECT possibly associated with longer remission. Higher doses, more frequent administration, and maintenance ECT or ketamine appear to prolong remission, and continuing oral antidepressants may extend it further. This systematic review of 13 studies found no direct head-to-head comparisons of time-to-relapse between the two treatments that met inclusion criteria, preventing formal statistical analysis. The review excluded studies involving psychotic depression, limiting generalizability to those populations.
Journal of affective disorders
April 15, 2026
Jen-Ping Chen, Chih-Wei Hsu, Yi-Ting Chen et al.
Among adults with treatment-resistant depression, repetitive transcranial magnetic stimulation (rTMS) was associated with fewer medical complications than esketamine over the first year, including lower risks of hospitalization, arrhythmia, and any injury. Suicide-related outcomes were broadly comparable overall, though esketamine showed a protective advantage during the 30-90-day interval and among patients aged 45-65 years. The analysis used target trial emulation with propensity score matching on 50 covariates, drawing on electronic health records of 1,690 matched patients per treatment group. The findings suggest rTMS has a more favorable overall medical safety profile, while suicide risks were similar except for specific subgroups and time periods.
Journal of affective disorders
April 15, 2026
Gia Han Le, Sabrina Wong, Danica E Johnson et al.
4 citations
Ketamine and esketamine rapidly reduce depression in people with treatment-resistant depression and bipolar depression, but the synaptic mechanisms behind dosing and durability are unclear. This review of 61 clinical and 17 preclinical studies found that a single 0.5 mg/kg intravenous infusion produces antidepressant effects peaking at 24 hours and fading over 2-3 days. Early neurophysiological changes appear within 3-8 hours, consolidate by 24 hours, and are rarely detected beyond 3 days. Twice-weekly and thrice-weekly dosing produce comparable four-week outcomes, and weekly maintenance reduces relapse risk. Ketamine may open a plasticity window lasting about 2-3 days, and aligning dosing intervals with this window could optimize durability while minimizing drug exposure.
Transl Psychiatry
April 10, 2026
1 citation
A target trial simulation using real-world data suggests that esketamine, when added to standard antidepressant treatment, maintains effectiveness and safety over a sustained period for people with major depressive disorder. The analysis, designed to mimic a randomized trial, found that patients receiving esketamine showed continued improvement in depressive symptoms without unexpected safety concerns. The findings support the long-term use of esketamine as a treatment option for major depressive disorder.
Reviews on recent clinical trials
April 7, 2026
Ritika Saun, Aakriti Garg, Mohd Ashif Khan
In adults with treatment-resistant depression, intranasal esketamine plus an antidepressant improved depressive symptoms within 24 hours, as measured by the MADRS scale (average 3.44 points greater reduction than placebo). However, esketamine raised the risk of elevated blood pressure threefold and dissociation nearly sixfold. The analysis of nine randomized controlled trials supports esketamine as a fast-acting option, but short follow-up periods, varying dosing protocols, and the notable side-effect profile limit broader conclusions. Long-term safety and durability of response remain insufficiently studied.