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.
Therapeutic advances in psychopharmacology
January 1, 2023
Anya Ragnhildstveit, Jeremy Roscoe, Lisa C Bass et al.
49 citations
PTSD has few effective pharmacological treatments, and trauma-focused psychotherapies are limited by provider shortages and low patient engagement, often leading to chronic illness and reduced quality of life. Ketamine, an NMDA receptor antagonist already indicated for major depression with rapid antidepressant effects, shows transdiagnostic potential. A synthesis of clinical evidence—including case reports, chart reviews, open-label studies, and randomized trials—reveals high heterogeneity in presentation and treatment approach but encouraging signals of safety, efficacy, and durability. Future research directions are discussed.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
November 1, 2024
Ruth H Asch, Chadi G Abdallah, Richard E Carson et al.
11 citations
A review describes the development of PET radiotracers targeting the synaptic vesicle glycoprotein 2A (SV2A), which allows measurement of synaptic density in living brains. In depression, lower SV2A density is found in people with significant depressive symptoms. A ketamine challenge was used to examine synaptogenesis in vivo. The authors stress the value of combining clinical imaging with animal model studies, presenting preliminary findings from chronic stress models. Methodological challenges and future directions for SV2A imaging, possibly alongside other neural markers, are discussed.
iScience
January 16, 2026
Amir Valizadeh, John D Roache, Xinyu Zhang et al.
2 citations
Post-traumatic stress disorder varies greatly in its clinical and biological features, making treatment difficult. The largest randomized trial of ketamine for PTSD found no overall benefit over placebo, highlighting the need to identify which patients might respond. Using pre-treatment blood DNA methylation profiles and clinical data from that trial, machine learning models predicted treatment response. A model based on 1,208 methylation sites outperformed models using only clinical variables, and combining both data types improved accuracy further. The methylation-derived score identified responders with 92.9% accuracy. Predictive methylation sites were near genes involved in glutamatergic signaling, immune regulation, and known PTSD risk loci, suggesting peripheral DNA methylation patterns can guide precision pharmacotherapy for PTSD.