Psychiatry research
September 1, 2026
Isis Lunsky, Gilmar Gutierrez, Xena Wang et al.
Postpartum depression (PPD) is common and harmful if untreated, with few effective prevention strategies. Ketamine and esketamine are rapid-acting antidepressants showing promise for PPD. This review searched five databases for peer-reviewed randomized controlled trials, pilot studies, and observational studies examining ketamine or esketamine for PPD prevention during pregnancy or postpartum, for both cesarean and vaginal deliveries. A network meta-analysis and narrative synthesis were used. Thirty-six studies were identified; five included vaginal delivery, thirty included cesarean section, and one did not specify delivery mode. Results suggested that ketamine and esketamine were well tolerated and may reduce PPD risk. However, data quality was low to very low, so results should be interpreted cautiously. More high-quality studies are needed.
Psychiatry research
August 1, 2026
Pietro Carmellini, Andrea Fagiolini, Mario Pinzi et al.
In a real-world clinic, intravenous ketamine reduced depressive symptoms in patients with treatment-resistant unipolar and bipolar depression. Both groups improved significantly, but those with bipolar depression showed faster and greater improvement starting at two weeks and lasting through three months. Dissociative side effects were mild and did not increase over time; women with unipolar depression reported higher dissociative symptoms at three months. No sex differences in antidepressant efficacy were found. The findings suggest ketamine is effective for treatment-resistant depression, with stronger benefits for bipolar depression.
Psychiatry research
July 1, 2026
Yao Xiao, Ping Xie, Danlei Li et al.
A network meta-analysis of 18 randomized controlled trials (1722 participants) compared pharmacological treatments for postpartum depression. Compared with placebo, saffron, fluoxetine, esketamine, brexanolone, and zuranolone showed signals of improvement in depressive symptom severity. Fluoxetine, saffron, and zuranolone were associated with higher response rates, though estimates for fluoxetine and saffron were imprecise. Brexanolone was the only intervention showing a statistically significant improvement in remission, but it may have a potentially unfavourable acceptability signal based on all-cause discontinuation. Zuranolone was associated with an increased incidence of adverse events. The evidence is limited by sparse networks, imprecision, and clinical heterogeneity, so findings should be interpreted cautiously.
Psychiatry research
June 16, 2026
Filippo Mazzoni, Fabiola Raffone, Arianna De Ciechi et al.
Among 90 outpatients with treatment-resistant depression, half also had borderline personality disorder (BPD). Depressive symptoms, measured by the MADRS scale, improved substantially over six months of intranasal esketamine treatment. The BPD group showed faster early improvement, and from one month onward had higher response rates (≥50% reduction in symptoms). Remission rates at six months were similar between groups (48.9% with BPD vs. 57.8% without). Anxiety and impulsivity decreased across the whole sample, and cognitive function did not worsen. No serious adverse events or dropouts occurred. Comorbid BPD did not hinder the overall remission outcome.
Psychiatry research
April 1, 2026
Wen-Huei Siao, Tzong-Shi Wang, Liang-Chun Wang et al.
Ketamine, a drug that blocks NMDA receptors and produces schizophrenia-like effects, causes different behavioral responses depending on the mouse strain and dose. Adolescent mice from four strains—C57BL/6J, DBA, BALB/c, and 129S1—received ketamine injections of 0, 25, or 50 mg/kg, and their movement in an open field was tracked. Before and after treatment, locomotor activity varied significantly among strains, with C57BL/6J mice most active and 129S1 mice least active. Ketamine dose-dependently increased movement in C57BL/6J mice, caused brief excitation in DBA mice at 25 mg/kg, delayed excitation in BALB/c mice at 50 mg/kg, and minimal changes in 129S1 mice. These findings demonstrate that genetic background and dose modulate ketamine sensitivity during adolescence.
Psychiatry research
June 1, 2025
Flávia Vieira, Ana Teresa Caliman-Fontes, Breno Souza-Marques et al.
A systematic review of 46 studies on ketamine and its enantiomers for major depressive disorder identified 16 assessment tools used to measure suicidal behavior. Most were explicit, clinician-rated scales such as the Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HAM-D), and Beck Scales for Suicide Ideation. Only the Suicide Ideation and Behavior Assessment Tool (SIBAT) was specifically developed for rapid-acting antidepressant trials. The variety of instruments used across studies makes comparisons difficult. The MADRS is suggested as a reasonable choice for assessing suicidal behavior in this context, though no single tool is universally preferable.
Psychiatry research
January 1, 2025
Li Kevin J, Slama Natalie E, Chen Ingrid et al.
Patients with treatment-resistant depression who received intravenous ketamine infusions (0.5 mg/kg over 40 minutes twice weekly for three weeks) were 72% more likely to achieve a 50% or greater reduction in depression symptoms compared to similar patients receiving standard medication management. The study followed 570 adults in a large healthcare system, matching groups on sex, race, age, and baseline depression severity. Although the ketamine group showed a higher remission rate (8% versus 5%), this difference was not statistically significant. Co-occurring anxiety and personality disorders, as well as more severe baseline depression, predicted worse outcomes regardless of treatment.
Psychiatry research
August 1, 2023
Jin Liu, Xiaotian Zhao, Xiyu Wei et al.
A double-blinded, placebo-controlled randomized trial tested whether nitrous oxide (N2O) improves cognitive function in 44 patients with treatment-resistant depression. Thirty-four patients completed cognitive tests before treatment and at 1 and 2 weeks after a one-hour inhalation of 50% N2O/50% oxygen or placebo (50% air/50% oxygen). Although N2O did not produce a significant antidepressant effect at 1 week, patients who received N2O showed better executive function at 1 week compared with placebo, and this improvement remained after controlling for changes in depressive symptoms. No significant differences were found in subjective cognitive function, processing speed, or attention over the 2-week follow-up. The results suggest N2O may have a pro-cognitive effect on executive function independent of mood improvement.
Psychiatry research
November 1, 2022
Danfeng Yan, Bangshan Liu, Xiyu Wei et al.
A single one-hour inhalation of 50% nitrous oxide (N2O) mixed with oxygen rapidly alleviated depression in patients with treatment-resistant depression in China, but the effect lasted no more than one week. In a double-blind, placebo-controlled trial, 44 patients were randomized to receive either 50% N2O or a placebo mixture. Depression scores on the Hamilton Depression Rating Scale were significantly lower in the N2O group at two hours and 24 hours after treatment, but no significant difference remained at one week or two weeks. Patients receiving N2O reported more adverse events, all of which resolved within 24 hours, and no serious adverse events occurred.