Psychiatry research
July 1, 2025
Hiroe Hu, Alaina N Tillman, Miyu Fujita et al.
2 citations
A systematic review of 30 studies suggests that ketamine and, to a lesser extent, d-cycloserine may enhance empathy and prosocial behavior. These glutamate receptor modulators appear to alter self- and other-perception by changing activity in brain regions linked to empathetic concern and mentalizing—the ability to understand one's own and others' thoughts and feelings. The findings point toward potential therapeutic applications for conditions involving impaired empathy and prosocial behavior, such as mood, neurodevelopmental, psychotic, and personality disorders.
Bipolar disorders
April 2, 2025
Adam Fijtman, Mani Yavi, Abigail Vogeley et al.
2 citations
Ketamine rapidly reduces depressive symptoms in treatment-resistant depression but does not improve working memory, attention, or concentration. In a crossover trial, 21 individuals with treatment-resistant depression (14 with bipolar disorder, 7 with major depressive disorder) received ketamine or placebo infusions. Brain activity measured by magnetoencephalography during a working memory task showed increased gamma power in the parieto-occipital junction and decreased gamma power in the posterior superior temporal sulcus and inferior frontal gyrus after ketamine compared to placebo. These distinct gamma power changes in brain regions linked to attention and working memory suggest that ketamine alters neural activity without improving cognitive performance, highlighting the need for further research into its neurobiological mechanisms.
JAMA psychiatry
July 1, 2026
Sung Ryul Shim, Hye Su Jeong, Tanner J Bommersbach et al.
1 citation
A systematic review and meta-analysis of 26 randomized clinical trials with 1,166 patients experiencing a major depressive episode found that intravenous ketamine infusions significantly reduce suicidal and depressive symptoms in the acute phase. A single ketamine infusion lowered suicidal symptoms at 24 hours and at 1 month, and repeated infusions produced similar reductions. Depressive symptoms decreased significantly from 4 hours through 1 week after a single infusion and after repeated infusions. Serious adverse events were unrelated to the interventions, and other side effects were transient. Longer-term outcomes remain unclear.
Journal of neuroendocrinology
January 1, 2026
Hiroe Hu, Yoojin Lee, Alaina N Tillman et al.
1 citation
People with both major depression and post-traumatic stress disorder (PTSD) have lower baseline levels of copeptin, a stable marker of vasopressin secretion, and a blunted reduction in copeptin after a single low-dose ketamine infusion compared to those with depression alone. Copeptin levels were unrelated to depression diagnosis or symptom severity of depression, anxiety, PTSD, anhedonia, suicidal ideation, or childhood trauma, but higher copeptin was linked to verbal aggression, an association weakened by PTSD. These findings point to a possible biological subtype of reduced vasopressin activity in co-occurring depression and PTSD, suggesting copeptin may serve as a peripheral biomarker for central vasopressin-driven circuits in neuropsychiatric disorders.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
June 16, 2026
Nadia Hejazi, Mina Kheirkhah, Brady Riedner et al.
Slow-wave activity (SWA) during early non-rapid eye movement sleep is lower in people with treatment-resistant depression (TRD) than in healthy volunteers. Ketamine, but not placebo, increases SWA in TRD patients, especially those who respond to treatment, while having no effect on SWA in healthy volunteers. Ketamine also improves overall sleep in TRD patients by increasing total sleep time and sleep efficiency and reducing sleep latency. The increase in SWA after ketamine lessens with age. The findings suggest that ketamine's antidepressant effects are closely tied to its modulation of early sleep SWA and its ability to improve sleep architecture in TRD.
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.
Journal of affective disorders
December 15, 2024
Rodrigo Machado-Vieira, Gregory H Jones, Alan C Courtes et al.
Fatigue, a multidimensional condition that often overlaps with depression, responds only modestly to standard antidepressants and mood stabilizers but has shown positive response to intravenous ketamine, which is limited by cost and access. This study evaluated a single 50 mg dose of intranasal ketamine in 28 individuals with major depressive disorder or bipolar depression, about 60% of whom also had alcohol use disorder. The group by time interaction for the NIH-Brief Fatigue Inventory score was significant, favoring intranasal ketamine over placebo at 4, 24, and 48 hours post-treatment. Intranasal ketamine was well-tolerated with minimal adverse effects. The findings suggest intranasal ketamine induces rapid anti-fatigue effects and may serve as an alternative rapid-acting option for fatigue across different medical conditions.