American Journal of Psychiatry
October 3, 2017
S. Wilkinson, Elizabeth D. Ballard, M. Bloch et al.
680 citations
A single dose of ketamine rapidly reduces suicidal thoughts within one day and for up to one week in depressed patients with suicidal ideation. The effect is moderate to large and partially independent of changes in depressive symptoms. The analysis combined data from 167 participants across 10 studies comparing ketamine to a placebo (saline or midazolam). Ketamine significantly improved clinician-rated and self-reported suicidal ideation, though not on one self-report measure (the Beck Depression Inventory). The authors call for further research on long-term safety and suicide risk reduction before clinical use.
The International Journal of Neuropsychopharmacology
September 12, 2011
Oz Malkesman, Daniel Austin, Tyson Tragon et al.
91 citations
D-serine, a co-agonist at NMDA receptors, produces antidepressant-like effects in rodents. A single acute dose of D-serine reduced immobility in the forced swim test without affecting motor function, reversed sexual reward-seeking deficits caused by serotonin depletion, and reversed learned helplessness behavior. Mice lacking NMDA receptor NR1 subunits in forebrain excitatory neurons showed a depression-like phenotype and did not respond to D-serine. These findings suggest D-serine has antidepressant-like effects and support the idea of complex glutamatergic dysfunction in depression, though it remains unclear whether D-serine shares a convergent mechanism with NMDA antagonists like ketamine.
Journal of Affective Disorders
May 1, 2019
Wei Zheng, Xiaohong Li, Xiao-Min Zhu et al.
57 citations
An updated meta-analysis of 17 randomized controlled trials involving 1,035 people with major depressive disorder found that adding ketamine alone to electroconvulsive therapy does not improve depressive symptoms compared with other anesthetic agents at any time point. Combining ketamine with other anesthetics showed a short-term advantage in reducing depressive symptoms early in treatment, but this benefit did not persist after the full course of ECT or at the end of the study. Most subgroup analyses confirmed the lack of significant effect. Ketamine alone increased blood pressure more than other anesthetics. Results for neurocognitive function were mixed.
National Science Review
September 5, 2025
Huoqing Luo, Ming Chen, Yingjie Ning et al.
1 citation
Ketamine produces rapid antidepressant effects by both blocking NMDA receptors and increasing serotonin levels through inhibition of the serotonin transporter (SERT). A cryogenic electron microscopy structure shows ketamine binding to SERT's central site. The elevated serotonin activates vasoactive intestinal peptide (VIP)-expressing interneurons, a cell type essential for ketamine's rapid effects. Inhibiting these neurons blocks the antidepressant actions, identifying a specific neural pathway. This dual mechanism offers potential strategies for developing rapidly acting antidepressants.
Pharmacological research
July 1, 2026
Yang Zhou, Wanchen Sun, Yuxuan Fu et al.
Among patients undergoing major surgery who had moderate-to-severe depressive symptoms before the operation, a single intraoperative dose of esketamine led to a higher rate of symptom remission three days after surgery compared with a placebo. In a randomized, double-blind trial of 435 patients, 28.3% in the esketamine group achieved remission versus 11.3% in the placebo group. Acute pain rates did not differ between groups. Esketamine treatment requires monitoring for possible dissociative side effects, and its clinical use for depressive symptoms should weigh benefits against risks.
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
July 1, 2022
Zhian Liu, Lichengxi Si, Tianyu Wang et al.
By converting high-density electroencephalogram (EEG) signals recorded from the scalp into cortical signals using source estimation, researchers examined how propofol alters consciousness. In 20 healthy adults, they filtered alpha-band activity and calculated pairwise orthogonal power envelope connectivity (PEC) across 68 brain regions. A statistical method (LASSO) identified the fewest PECs needed to distinguish baseline from moderate sedation. Most of those PECs involved regions of the default mode network, and changes in thalamocortical and frontal-parietal connectivity matched those seen with direct neuroimaging. A classifier based on the selected PECs achieved over 70% accuracy in distinguishing the two states, suggesting this approach could aid future anesthesia depth monitoring.
International Journal of Neural Systems
January 23, 2020
Wen Shi, Yamin Li, Zhian Liu et al.
During propofol-induced sedation, a distinct EEG microstate pattern—a posterior central maximum labeled microstate F—emerges and becomes prominent. Its coverage, occurrence, and power significantly increase in moderate sedation, and the transition from rest to sedation is accompanied by a significant rise in mean energy across all frequency bands in this microstate. The findings suggest that microstate F is closely linked to propofol-altered consciousness and may derive from the canonical anterior-posterior microstate C. The work also advances methods for analyzing microstates in the frequency domain using multivariate empirical mode decomposition and Hilbert-Huang transform.