Annual Review of Medicine
October 23, 2014
Chadi G. Abdallah, Gerard Sanacora, Ronald S. Duman et al.
420 citations
Ketamine, a glutamate-based antidepressant, can rapidly alleviate depression within hours of treatment. Replicated evidence shows its rapid and potent effects in treatment-resistant depression. Preclinical and biomarker studies have begun to explain the mechanism behind these rapid effects, offering new insights into depression's biology and identifying potential treatment targets. This article discusses ketamine's efficacy, safety, and tolerability, summarizes depression's neurobiology, reviews the mechanisms of ketamine's rapid antidepressant effects, and considers prospects for next-generation rapid-acting antidepressants.
Depression and Anxiety
April 6, 2016
Chadi G. Abdallah, Thomas G. Adams, Benjamin Kelmendi et al.
204 citations
Major depressive disorder is a common psychiatric condition that often responds poorly to traditional antidepressants, which can take weeks to work. Over the past two decades, the NMDA receptor antagonist ketamine has attracted attention because a single low dose produces rapid antidepressant effects in people with treatment-resistant depression. Evidence from animal and human studies suggests that ketamine triggers a surge of glutamate, initiating a cascade that promotes synaptogenesis and reverses stress-related damage, especially in the prefrontal cortex. This review covers the neurobiology of stress-related depression, the safety and efficacy of ketamine, its mechanism of action, and predictors of treatment response, along with research limitations and future directions.
Annals of the New York Academy of Sciences
February 27, 2015
Chadi G. Abdallah, Lynnette A. Averill, John H. Krystal
117 citations
Ketamine produces rapid and robust antidepressant effects in patient populations that often show little or no response to traditional antidepressants, and it is generally well tolerated with only transient mild-to-moderate adverse effects during infusion. However, the optimal dosing, route of administration, and safety of chronic treatment remain uncertain. This review describes ketamine's clinical effects, its neurobiological mechanisms, and how these may illuminate the neurobiology of depression, relevant biomarkers, and treatment targets. The authors also suggest directions for future research to improve psychopharmacologic interventions for depressive and trauma-related disorders.
European journal of psychotraumatology
August 29, 2023
Lihong Jiang, Amanda J. F. Tamman, Christopher L. Averill et al.
8 citations
Early trauma is linked to stronger glutamatergic synaptic strength in people with PTSD, measured via a novel in vivo marker called energy per cycle (EPC). In a sample of 34 adults (16 with PTSD, 18 healthy controls), higher early trauma correlated with higher EPC only in the PTSD group. Greater synaptic strength was associated with reduced behavioral inhibition, and EPC mediated stronger links between reward responsiveness and early trauma. These findings suggest that trauma-induced changes in synaptic plasticity may underlie psychiatric risk and point to potential targets for treatments like ketamine and psilocybin.
Psychiatric Annals
February 1, 2020
Lynnette A. Averill, Christopher L. Averill, Chadi G. Abdallah
6 citations
Ketamine's discovery as a rapid antidepressant has transformed drug development and understanding of chronic stress pathology. This review covers the history of NMDA receptor modulators leading to ketamine's psychiatric use, its rapid antidepressant and antisuicidal effects, a model of synaptic loss and dysconnectivity underlying chronic stress pathology, clinically relevant biomarkers and mechanisms, and how ketamine may both reverse chronic stress pathology and serve as a research tool. The authors discuss outstanding questions and the ongoing debate between optimism and concern about ketamine's widespread use.
medRxiv Preprint Server
April 10, 2020
Chadi G. Abdallah, Kyung-Heup Ahn, Lynnette A. Averill et al.
1 citation
preprint
A robust and reproducible brain connectivity fingerprint (CFP) was identified during ketamine infusion in healthy participants, characterized by reduced connectivity within primary cortices and the executive network, but increased connectivity between the executive network and the rest of the brain. This same CFP measured one week after treatment in major depressive disorder patients predicted response to eight weeks of sertraline, but not placebo. The findings suggest a brain network biomarker that links ketamine's acute effects to the mechanisms of conventional antidepressants.