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.
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.