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.
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.
Translational psychiatry
November 18, 2025
Jenessa N Johnston, Peixiong Yuan, Bashkim Kadriu et al.
2 citations
In neurons derived from induced pluripotent stem cells of five women with treatment-resistant depression (average age 40.2 years), both the glycoprotein reelin and the ketamine metabolite (2R,6R)-hydroxynorketamine increased expression of several synaptic proteins (GluA1, PSD-95, Dab1, Synapsin I, and p-ERK) within one hour, with effects declining by 24 hours. Gene expression changes were similar for both compounds, though only reelin upregulated mTORC1 signaling. The findings suggest that iPSC-derived neurons may serve as a useful in vitro model for studying treatment-resistant depression and testing potential therapeutics.
Translational psychiatry
April 21, 2026
Paul A Parcon, Amanda Bardhoshi, Amanda Olsen-Dufour et al.
Ketamine, a rapid-acting antidepressant, increases cyclic adenosine monophosphate (cAMP) activity in the brain within an hour of infusion, likely by affecting phosphodiesterase-4 (PDE4), an enzyme that normally terminates cAMP signaling. In rats given 10 mg/kg ketamine, binding of a radioligand to PDE4 increased by a mean of 24% (range 3%–42%); in rhesus macaques given 0.5 mg/kg, binding increased by a mean of 14% (range 12%–16%). A radioligand selective for the PDE4B subtype showed a mean increase of 28% (range 16%–37%) in monkeys. Control experiments ruled out blood-flow effects. The findings suggest that boosting cAMP activity through PDE4 inhibition, particularly the PDE4B subtype, may underlie ketamine's rapid antidepressant effects and point to a common pathway for antidepressant action.
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.