BMC pharmacology & toxicology
January 30, 2026
Enayatollah Seydi, Sana Ghanizadeh, Farzaneh Jokar et al.
Ketamine, a drug with various pharmacological effects, can cause brain side effects and neurotoxicity by inducing oxidative stress and impairing mitochondrial function. In rat brain neurons, ketamine reduced cell viability (half-maximal inhibitory concentration of 4 µM) and, at 2, 4, and 8 µM, increased reactive oxygen species, damaged mitochondrial and lysosomal membranes, and raised cytochrome c release. The antioxidant α-tocopherol at 10 µM prevented these effects caused by 8 µM ketamine: it reduced oxidative stress, preserved membrane integrity, and decreased apoptosis signaling, suggesting a potential protective role against ketamine neurotoxicity.
Journal of affective disorders
January 30, 2026
Yao-Zu Li, Cai-Qun Zhao, Mu-Yan Zuo et al.
A multimodal therapy combining esketamine with dexmedetomidine patient-controlled sleep (PCSL) was associated with sustained improvements in depressive symptoms and sleep quality over 6 months in 233 patients with treatment-resistant depression. Antidepressant response rates were 62% at 1 month, 59.73% at 3 months, and 58.49% at 6 months. Use of PCSL was linked to response at all time points, while additional esketamine during follow-up was associated with response at 3 months but not statistically significantly at 6 months. Age and disease duration also influenced response. No serious adverse events occurred.
Cell biology and toxicology
January 30, 2026
Jia-Yi Wei, Peng Lv, Jiayu Zhang et al.
Repeated ketamine exposure over seven days causes anxiety-like and depressive-like behaviors along with cognitive deficits in mice. The dopamine receptor DRD1 plays a key role in these effects: activating DRD1 produces anxiety-like behavior similar to ketamine and worsens ketamine's effects, while blocking DRD1 partially reduces anxiety but worsens depression. Ketamine triggers apoptosis (cell death) in HT22 cells by suppressing Akt/Gsk3β phosphorylation through DRD1. In mice, ketamine promotes neuronal apoptosis in the hippocampus and prefrontal cortex; blocking DRD1 partially reduces this apoptosis, but knocking down DRD1 in neurons unexpectedly increases both apoptosis and anxiety-like behavior.
European journal of anaesthesiology
January 29, 2026
Tiantian Chu, Xiaoling Peng, Keliang Wan et al.
2 citations
A single dose of esketamine given intravenously around the time of cesarean section, followed by 24 hours of low-dose esketamine in patient-controlled pain relief, reduced the overall incidence of postpartum depression within three months after childbirth in first-time mothers who were not already depressed. The total rate of postpartum depression was 11.59% in the esketamine group versus 20.89% in the saline control group. The benefit was most evident at 7 days postpartum, with no significant differences at 1, 2, or 3 months individually. Mild side effects like dizziness, hallucination, and dissociation occurred in some women. The treatment appears relatively safe and prevents postpartum depression in the short term.
The journal of ECT
January 29, 2026
Sergi López-rodríguez, Aida De Arriba-Arnau, José Manuel Menchón et al.
1 citation
Combining electroconvulsive therapy (ECT) with intranasal esketamine (ESK) may offer sustained improvement for adults with severe treatment-resistant depression who had only partial benefit from either treatment alone. In four patients aged 50 to 72, the combination reduced depression scores by an average of 58% over 24 weeks, with no relapses. Two patients who added the complementary treatment to partial monotherapy showed symptom reductions of 50% and 37%. Two others who were already responding to maintenance ECT had further improvements of 62% and 83%, allowing ECT sessions to be spaced from weekly to every two to three weeks. Side effects were mild and temporary, including brief dissociation and post-ictal confusion. These findings suggest the combination is feasible and warrants controlled trials.
Journal of affective disorders
January 28, 2026
Clara De Oliveira Lapa, Thiago Viola, Rodrigo Delfino et al.
3 citations
Intranasal esketamine substantially reduces depressive symptoms and increases remission rates over time in patients with treatment-resistant depression treated in routine clinical practice. A meta-analysis of nine observational studies found a large effect size (Hedges' g = -1.98) and that patients were about five times more likely to achieve remission at three months compared with the induction phase (odds ratio = 5.1). Treatment effectiveness was not influenced by gender or the presence of anxiety, personality, or substance use disorders. Any adverse event occurred in 82% of patients, most commonly dissociation (49%). The findings support esketamine's effectiveness and tolerability in real-world settings, though the observational design and lack of control groups warrant cautious interpretation.
The American journal on addictions
January 28, 2026
Mariana C De Oliveira, Cláudia C De Araujo Palmeira, André B Negrão et al.
1 citation
A 25-year-old woman with opioid use disorder, chronic pain, and major depressive disorder received eight weekly intravenous ketamine infusions (0.5 mg/kg) alongside a gradual reduction of her methadone dose. After the protocol, her methadone dosage was cut by 50%, and she experienced better control of pain and cravings, fewer withdrawal symptoms, and increased participation in psychotherapy. The report suggests that ketamine-assisted bridge therapy may help support opioid tapering in patients with multiple co-occurring conditions.
Journal of perianesthesia nursing : official journal of the American Society of PeriAnesthesia Nurses
January 28, 2026
Karina Bridges, Ionela Morosanu, Lilian Njoki et al.
A case report describes an unusual occurrence of postoperative delirium in a patient who underwent robotic-assisted prostatectomy under an opioid-free anesthesia protocol that included intraoperative infusions of ketamine, lidocaine, and magnesium. The report details the clinical presentation, contributing factors, and management of this complication, offering educational insights for clinicians using similar multimodal analgesic strategies.
Brazilian Journal of Health Review
January 28, 2026
Ketamine appears to be an alternative treatment for bipolar depression when first- and second-line medications are not effective, according to a review of six clinical trials published between 2010 and 2021. Bipolar depression is the most common mood state in bipolar disorder, yet few studies have focused on its treatment. The review examined evidence on ketamine used either as an adjuvant or as monotherapy. The results suggest ketamine may be effective, but future studies are needed to confirm this.
Expert opinion on therapeutic targets
January 28, 2026
Gia Han Le, Roger S. McIntyre
1 citation
Up to half of adults with major depressive disorder who do not respond to two or more standard antidepressants may have treatment-resistant depression (TRD). Low-dose intravenous ketamine, intranasal esketamine, and oral dextromethorphan are the first glutamatergic treatments to work rapidly and robustly for TRD, but their exact mechanisms are unclear. This review integrates evidence that elevated tonic NMDA receptor currents, mainly through NR2C/D subunits, underlie TRD. Ketamine, esketamine, and dextromethorphan selectively dampen these currents to produce rapid and sustained antidepressant effects. Ketamine and esketamine's affinity for NR2A/B subunits likely drives dissociative effects not seen with dextromethorphan. Future drug development should focus on subunit-biased ligands.
The Brown University Psychopharmacology Update
January 24, 2026
A randomized trial found that up to eight infusions of ketamine were not more effective than a psychoactive placebo (midazolam) in reducing depressive symptoms among patients receiving inpatient treatment for depression. Patients receiving ketamine also showed no improvement relative to those receiving midazolam on measures of cognition and quality of life. The results suggest that ketamine does not provide additional benefit over a psychoactive placebo in this inpatient setting.
Journal of affective disorders
January 23, 2026
Reinhard Janssen-Aguilar, Jithin Joseph, Huda Al-Shamali et al.
In a retrospective chart review of 209 adults with treatment-resistant depression treated with intravenous ketamine, depressive and anxiety symptoms improved significantly over four or six infusions, but the improvements were modest and highly variable across individuals. Anxiety symptoms improved more slowly and less robustly than depressive symptoms. End-of-treatment response and remission rates were numerically higher after six infusions than after four, but the difference was not statistically significant. Four distinct patterns of symptom change emerged for both depression and anxiety, highlighting the heterogeneity of treatment response. Durability after six infusions could not be assessed because follow-up data were available only for the four-infusion group.
BJPsych open
January 23, 2026
Nawfel Ayad, Karim Abdel Aziz, Samer Makhoul et al.
2 citations
In a small real-world study of 20 adults with treatment-resistant depression who received at least 100 sessions of intranasal esketamine alongside oral antidepressants over an average of 2.5 years, depression and anxiety scores significantly decreased. 85% of patients showed improvement in depressive severity, with 25% achieving remission; 65% improved in anxiety severity, and 20% reached remission. Esketamine was generally well tolerated with mild, transient side effects and no serious adverse events, though 20% of patients developed urinary symptoms suggestive of cystitis, indicating a need for ongoing monitoring. The findings support the long-term effectiveness and acceptable safety profile of esketamine in complex clinical populations.
Figshare
January 23, 2026
David Eckert, Siegfried Kasper
Treatment-resistant depression is a major clinical challenge, and guidelines recommend different pharmacological augmentations. A systematic review of head-to-head studies comparing lithium, quetiapine, and esketamine found only four trials: three comparing lithium and quetiapine, and one comparing esketamine and quetiapine. All three agents are effective, with a descriptive superiority of esketamine over quetiapine and of quetiapine over lithium. The results argue for re-evaluating treatment algorithms, but because the drugs differ in side effects, contraindications, and pharmacological profiles, embedding them in a comprehensive clinical context is important.
Frontiers in Psychiatry
January 22, 2026
Jae Sevelius, Rachel Lynn Golden, B. Stott et al.
1 citation
A novel group-based ketamine-assisted psychotherapy program called Kindred, which integrates cognitive processing therapy, was tested with eight transgender and gender-expansive adults. The nine-week intervention alternated ketamine dosing sessions with cognitive skills-building and integration sessions. All participants completed the program and reported high satisfaction. Significant reductions in depression, anxiety, and cognitive fusion scores were observed, alongside qualitative reports of decreased shame, suicidality, and internalized transphobia. Participants identified group belonging, peer validation, and shared identity as important therapeutic factors. The findings suggest Kindred is a feasible and promising intervention for addressing mental health symptoms related to identity-based trauma in this population.
Pharmacological reports : PR
January 22, 2026
Taichi Goto, Joy D Kreskow, Alexander L R Ross et al.
A small pilot trial tested whether a single low dose of ketamine (0.5 mg/kg) can reduce fatigue in people with chronic illnesses such as cancer, fibromyalgia, chronic fatigue syndrome, or lupus. Ten participants received both ketamine and the active placebo midazolam in random order, with a washout period between treatments. Because fatigue levels differed between the two study periods, results were analyzed separately. In the first period, fatigue scores dropped 21.0% after ketamine and 17.7% after midazolam; in the second period, the drops were 10.9% and 12.6%, respectively. The differences were not statistically significant, but the ketamine group showed a peak 38.7% reduction one day after infusion. The authors suggest future studies avoid crossover designs and find a better active placebo.
Indian journal of psychological medicine
January 22, 2026
Zaid Ahmad Wani, Rajnish Raj, Shabir Ahmad Dar et al.
In a retrospective study of 41 patients in India with major depressive disorder, bipolar depression, or suicidal ideation, oral ketamine therapy was associated with significant reductions in both depressive symptoms and suicidal thoughts. Depression severity, measured by the Hamilton Depression Rating Scale, decreased by an average of 8.19 points, and suicidal ideation, measured by the Modified Scale for Suicidal Ideation, decreased by an average of 4.95 points after three sessions. Common side effects included dizziness, nausea, and hypertension; diarrhea was least common. The findings suggest oral ketamine is an effective and well-tolerated rapid-acting option for reducing depressive symptoms and suicidality, suitable for outpatient use in the Indian context.
Expert Opinion on Pharmacotherapy
January 22, 2026
Diana Orsini, Sara D Di Luch, Gabrielle F. M. Lovell et al.
A large body of evidence from clinical trials and real-world studies supports the antidepressant effects of intravenous ketamine and intranasal esketamine. Larger studies have provided reassuring safety data, including for long-term treatment. Alternative routes of administration show promise for scalability, but their efficacy relative to intravenous ketamine remains unclear. Preliminary data suggest ketamine may also be effective for bipolar disorders, personality disorders, posttraumatic stress, and obsessive-compulsive disorder. Further research is needed to optimize protocols, such as combining ketamine with other interventions. Challenges include functional unblinding, expectancy-related bias, and treatment costs.