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.
Advances in pharmacology (San Diego, Calif.)
January 1, 2020
Bashkim Kadriu, Elizabeth D Ballard, Ioline D Henter et al.
35 citations
Psychiatry is moving toward early identification and intervention to reduce the burden and duration of severe mental illnesses. The rapid-acting antidepressant ketamine has transformed understanding of antidepressant response and expanded treatment options for treatment-resistant depression. Efforts to characterize biomarkers of ketamine response aim to identify biologically enriched subgroups more likely to benefit. This chapter reviews translational biomarkers from imaging, electrophysiology, sleep, circadian rhythms, HPA axis function, metabolism, immune, (epi)genetic, and neurotrophic systems. Ketamine's properties may model new rapid-acting treatments. However, most studies focus on acute effects, and no biomarkers are ready for clinical use.
Translational psychiatry
June 4, 2024
Elizabeth D Ballard, Deanna Greenstein, Philip T Reiss et al.
16 citations
Ketamine, a drug that modulates the glutamate system, is linked to changes in sleep, depression, and suicidal thoughts. In a randomized, double-blind, crossover trial, 36 people with treatment-resistant major depression and 25 healthy volunteers underwent polysomnography before and after receiving ketamine or placebo. At baseline, those with depression had less total sleep time and shorter REM latency. Ketamine increased slow-wave (delta) brain activity early in the night and both alpha and delta activity later, compared to placebo. However, ketamine did not significantly alter sleep arousal metrics or mediate its antidepressant or anti-suicidal effects through sleep changes. The findings suggest sleep-related variables are part of broader neurobiological shifts after ketamine.
Journal of affective disorders
July 15, 2024
Kelly T Hurst, Abigail Vogeley, Deanna K Greenstein et al.
8 citations
People who received ketamine for depression in early clinical trials at the National Institute of Mental Health (NIMH) were more likely to obtain ketamine or esketamine after leaving the research setting. Among 203 former participants followed up an average of nine years later, 25.6% had originally received ketamine at the NIMH. Those who had received ketamine were significantly more likely to have used ketamine or esketamine afterward. However, receiving ketamine at the NIMH was not linked to higher rates of suicide attempts, psychiatric hospitalizations, dissociation, hallucinations, or attempts to obtain non-prescribed ketamine. Participants who used ketamine or esketamine after discharge reported more depressive symptoms. No symptoms indicating abuse were reported. The findings highlight the need for long-term monitoring of patients receiving rapid-acting antidepressants.
Journal of affective disorders
March 1, 2025
Elizabeth D Ballard, Lucinda Neely, Laura Waldman et al.
4 citations
Suicidal ideation, depression, hopelessness, psychological pain, and traumatic stress are all elevated during a suicide crisis and respond to a single ketamine infusion. In a study of 118 adults spanning the suicide risk continuum, 14 high-risk individuals who had recently attempted or seriously considered suicide were compared with those whose crisis had resolved. A subset of 10 high-risk participants received open-label ketamine (0.5 mg/kg). Results were mixed depending on the assessment used, but all five clinical characteristics were elevated near the time of crisis and decreased after ketamine. The small sample and use of only one intervention limit the findings.
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.
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.