Molecular Psychiatry
September 7, 2022
Rebecca B Price, Nicholas Kissel, Andrew Baumeister et al.
80 citations
Ketamine given intravenously rapidly reduces depressive symptoms, with effects lasting at least a week. In an analysis of 17 randomized controlled trials with 809 participants, the benefit over placebo was larger for patients who had already failed two or more prior antidepressant trials. However, no patient-level clinical or demographic characteristics—such as age, sex, or diagnosis—could predict who would respond best, limiting the ability to personalize ketamine prescriptions. The findings confirm ketamine's broad effectiveness for depression but show that precision medicine approaches cannot yet guide treatment decisions.
Neuroscience and biobehavioral reviews
July 1, 2024
Mina Kheirkhah, Allison C Nugent, Alicia A Livinski et al.
13 citations
Music and ketamine each influence therapeutic outcomes, yet their combined use is rarely studied. This scoping review maps existing research on administering music alongside ketamine or esketamine in humans. Studies include healthy volunteers and patients of various ages, using different doses and treatment processes, with music played at varying times relative to drug administration. Research on music during ketamine anesthesia is included, as anesthesia drove early ketamine use. Recreational ketamine studies are excluded. The review is limited to English-language articles with no year restriction. It is the first comprehensive overview of music and ketamine/esketamine interplay, offering guidance for future study design.
The British journal of psychiatry : the journal of mental science
May 13, 2025
Shabnam Hossein, Manivel Rengasamy, Aiyedun Uzamere et al.
3 citations
Ketamine infusion most strongly alleviates sadness both immediately and during the first week after treatment, whereas improvements in suicidal thoughts emerge only after three to four weeks. In a secondary analysis of 152 adults with treatment-resistant depression (38.8% with suicidal ideation at baseline), those randomized to a single 40-minute intravenous infusion of ketamine (0.5 mg/kg) showed greater early improvement in sadness-related symptoms compared with saline. Network analyses revealed that ketamine increased connectivity among depressive symptoms, strengthening interrelationships between residual symptoms. The findings suggest that different depressive symptoms respond to ketamine with distinct time courses and possibly different mechanisms.
Brain, behavior, and immunity
April 4, 2025
Manivel Rengasamy, Benjamin Panny, Zakary Hutchinson et al.
3 citations
In adults with treatment-resistant depression, a single ketamine infusion did not produce detectable changes in blood markers of neurotrophic and inflammatory factors compared with a saline placebo, nor were those markers linked to depression improvement over five days. Among 133 participants, only one subgroup—those with a body-mass index below 25—showed an association: rising levels of interleukin-1 receptor antagonist in the first day after ketamine correlated with less reduction in depression symptoms. The results do not support the idea that peripheral neurotrophic or inflammatory factors mediate ketamine's rapid antidepressant effects, though central nervous system activity may still be involved.
Journal of psychopathology and clinical science
April 1, 2025
Shabnam Hossein, Mary L Woody, Benjamin Panny et al.
3 citations
Ketamine rapidly improves symptoms of treatment-resistant depression (TRD), but because TRD varies widely among patients, markers are needed to personalize treatment. This study measured brain functional connectivity during positive mood processing in 152 adults with TRD before they received either ketamine or a saline placebo. Two connectivity-based subgroups emerged: Subgroup A (110 patients) and Subgroup B (42 patients). Ketamine improved depression uniformly across both subgroups. However, among patients given saline, those in Subgroup B were more likely to show a placebo response 24 hours later than those in Subgroup A. Thus, brain connectivity patterns predicted placebo response but not ketamine response.
Biological psychiatry
April 15, 2025
Mary L Woody, Rebecca Rohac, Iya Cooper et al.
1 citation
A single intravenous dose of ketamine (0.5 mg/kg over 40 minutes) rapidly reduces attentional bias toward sad stimuli in adults with moderate-to-severe depression. A novel dual-probe video task measuring attentional bias showed good test-retest reliability at one week and one month before treatment. In two studies totaling 83 participants, attentional bias decreased from before to 24 hours after ketamine infusion. In the first study, attentional bias correlated with clinician-rated depressive symptoms at each pretreatment assessment. In the second study, reductions in attentional bias correlated with symptom improvement. The findings suggest that reducing attentional bias may be a cognitive mechanism underlying ketamine's rapid antidepressant effects.
Molecular psychiatry
November 1, 2024
H Nur Eken, Crystal Spotts, Benjamin Panny et al.
1 citation
A combination of ketamine infusion and a digital training program called automated self-association training (ASAT) produced more positive implicit self-associations immediately after treatment in adults with treatment-resistant depression, compared to control groups that received only one active component. These changes in implicit self-worth tracked with concurrent depression symptom improvement across all groups and specifically predicted longer-term depression relief at 30 days for the combined treatment group. The findings indicate that shifting implicit self-esteem during a post-ketamine 'plasticity window' is a key mechanism behind the combined treatment's antidepressant effect, confirming the intended cognitive target.
Journal of psychopharmacology (Oxford, England)
June 25, 2026
Pavan S Brar, Rebecca B Price, Stephen Ross et al.
Psychedelic compounds like psilocybin and LSD are being studied again as potential treatments, but research usually excludes people at risk for psychosis. This narrative review examines the historical and theoretical links between psychedelics and schizophrenia spectrum disorders (SSDs), including the psychotomimetic hypothesis. The authors compare the phenomenological experiences induced by psychedelics with those of SSDs, finding both overlap and important qualitative differences that challenge a simple equivalence. They review neural mechanisms involving serotonin, dopamine, and glutamate. Clinical evidence shows psychedelics can worsen existing psychotic illness and may trigger psychosis in vulnerable individuals, though the risk magnitude is not well quantified. The authors suggest potential therapeutic applications for carefully selected symptoms in stable patients using low-dose, controlled approaches and provide recommendations for managing psychosis-related risk.