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Carlos A. Zarate

National Institute of Mental Health, National Institutes of Health

85 papers in the library · 10,251 citations · publishing 2006-2026

Papers

Repurposing General Anesthetic Drugs to Treat Depression: A New Frontier for Anesthesiologists in Neuropsychiatric Care.

Anesthesiology August 1, 2024 Connor T A Brenna, Benjamin I Goldstein, Carlos A. Zarate et al. 19 citations

During the last 100 years, the role of anesthesiologists in psychiatry has focused primarily on facilitating electroconvulsive therapy and mitigating postoperative delirium and other perioperative neurocognitive disorders. The discovery of the rapid and sustained antidepressant properties of ketamine, and early results suggesting that other general anesthetic drugs (including nitrous oxide,...

Esketamine in depression: putative biomarkers from clinical research.

European Archives of Psychiatry and Clinical Neuroscience July 13, 2024 Jenessa N Johnston, Carlos A. Zarate, Mark D Kvarta 18 citations

The discovery of racemic (R, S)-ketamine as a rapid-acting antidepressant and the subsequent FDA approval of its (S)-enantiomer, esketamine, for treatment-resistant depression (TRD) are significant advances in the development of novel neuropsychiatric therapeutics. Esketamine is now recognized as a powerful tool for addressing persistent symptoms of TRD compared to traditional oral...

Ketamine's mechanism of action with an emphasis on neuroimmune regulation: can the complement system complement ketamine's antidepressant effects?

Molecular Psychiatry September 1, 2024 Brandi Quintanilla, Carlos A. Zarate, Anilkumar Pillai 17 citations

Over 300 million people worldwide suffer from major depressive disorder (MDD). Unfortunately, only 30-40% of patients with MDD achieve complete remission after conventional monoamine antidepressant therapy. In recent years, ketamine has revolutionized the treatment of MDD, with its rapid antidepressant effects manifesting within a few hours as opposed to weeks with conventional antidepressants....

Functional MRI markers for treatment-resistant depression: Insights and challenges.

Progress in Brain Research January 1, 2023 Vasileia Kotoula, Jennifer W. Evans, Claire Punturieri et al. 17 citations

Imaging studies of treatment-resistant depression (TRD) have examined brain activity, structure, and metabolite concentrations to identify critical areas of investigation in TRD as well as potential targets for treatment interventions. This chapter provides an overview of the main findings of studies using three imaging modalities: structural magnetic resonance imaging (MRI), functional MRI...

Are 24-hour motor activity patterns associated with continued rapid response to ketamine?

Neuropsychiatric Disease and Treatment October 1, 2018 Wallace C. Duncan, Elizabeth E. Slonena, Nadia S. Hejazi et al. 17 citations

PURPOSE: This study examined the links between 24-hour activity patterns (specifically, amplitude and timing of wrist activity) and the persisting qualities of clinical antidepressant response to the glutamatergic modulator ketamine. METHODS: Twenty-four-hour activity patterns were compared across 5 days of 24-hour activity rhythms in patients with major depressive disorder who displayed either...

Baseline Vitamin B12 and Folate Levels Do Not Predict Improvement in Depression After a Single Infusion of Ketamine

Pharmacopsychiatry June 23, 2014 Nancy B. Lundin, Mark J. Niciu, David A. Luckenbaugh et al. 17 citations

INTRODUCTION: Deficiencies in both vitamin B12 and folate have been associated with depression. Recently, higher baseline vitamin B12 levels were observed in individuals with bipolar depression who responded to the antidepressant ketamine at 7 days post-infusion. This study sought to -replicate this result by correlating peripheral vitamin levels with ketamine's antidepressant efficacy in...

Functional changes in sleep-related arousal after ketamine administration in individuals with treatment-resistant depression.

Translational Psychiatry June 4, 2024 Elizabeth D. Ballard, Deanna K Greenstein, Philip T Reiss et al. 16 citations

The glutamatergic modulator ketamine is associated with changes in sleep, depression, and suicidal ideation (SI). This study sought to evaluate differences in arousal-related sleep metrics between 36 individuals with treatment-resistant major depression (TRD) and 25 healthy volunteers (HVs). It also sought to determine whether ketamine normalizes arousal in individuals with TRD and whether...

Ketamine and Hydroxynorketamine as Novel Pharmacotherapies for the Treatment of Opioid Use Disorders.

Biological Psychiatry March 15, 2025 Anna Onisiforou, Andria Michael, Markos Apostolakis et al. 14 citations

Opioid use disorder (OUD) has reached epidemic proportions, with many countries facing high levels of opioid use and related fatalities. Although currently prescribed medications for OUD are considered lifesaving, they inadequately address negative affect and cognitive impairment, resulting in high relapse rates to nonmedical opioid use even years after drug cessation (protracted abstinence)....

Exploring the impact of music on response to ketamine/esketamine: A scoping review.

Neuroscience and Biobehavioral Reviews July 1, 2024 Mina Kheirkhah, Allison C. Nugent, Alicia A Livinski et al. 13 citations

Music and ketamine are both known to affect therapeutic outcomes, but few studies have investigated their co-administration. This scoping review describes the existing literature on the joint use of music and ketamine-or esketamine (the S(+) enantiomer of ketamine)-in humans. The review considers that extant studies have explored the intersection of ketamine/esketamine and music in healthy...

A Randomized, Double-Blind, Placebo-Controlled Pilot Trial of the Acute Antisuicidal and Antidepressant Effects of Intranasal (R,S)-Ketamine in Severe Unipolar and Bipolar Depression With and Without Comorbid Alcohol Use Disorder.

The Journal of Clinical Psychiatry April 24, 2024 Gregory H Jones, Courtney M Vecera, Ana C Ruiz et al. 13 citations

Objective: Although individuals with a family history of alcohol use disorder (AUD) have a superior antidepressant response to ketamine, outcomes in patients with current AUD remain unclear. This study sought to investigate whether intranasal (IN) racemic (R,S)-ketamine had antisuicidal and antidepressant effects in unipolar and bipolar depression and whether comorbid AUD conferred superior...

Entactogen Effects of Ketamine: A Reverse-Translational Study.

The American journal of psychiatry September 1, 2024 Evan M. Hess, Dede Greenstein, Olivia L Hutchinson et al. 12 citations

The authors sought to assess the prosocial, entactogen effects of ketamine. Pleasure from social situations was assessed in a sample of participants with treatment-resistant depression from randomized, double-blind, placebo-controlled studies, using four items of the Snaith-Hamilton Pleasure Scale (SHAPS) at five time points over 1 week following treatment with ketamine (0.5 mg/kg...

The role of dissociation in ketamine's antidepressant effects.

Nat Commun December 22, 2020 Elizabeth D. Ballard, Carlos A. Zarate 10 citations

Ketamine produces immediate antidepressant effects and has inspired research into next-generation treatments. Ketamine also has short term dissociative effects, in which individuals report altered consciousness and perceptions of themselves and their environment. However, whether ketamine's dissociative side effects are necessary for its antidepressant effects remains unclear. This perspective...

Hippocampal volume changes after (R,S)-ketamine administration in patients with major depressive disorder and healthy volunteers.

Scientific Reports February 24, 2024 Jennifer W. Evans, Morgan C Graves, Allison C. Nugent et al. 9 citations

The hippocampus and amygdala have been implicated in the pathophysiology and treatment of major depressive disorder (MDD). Preclinical models suggest that stress-related changes in these regions can be reversed by antidepressants, including ketamine. Clinical studies have identified reduced volumes in MDD that are thought to be potentiated by early life stress and worsened by repeated...

Long-term follow-up of participants in ketamine clinical trials for mood disorders.

Journal of Affective Disorders July 15, 2024 Kelly T Hurst, Abigail Vogeley, Deanna K Greenstein et al. 8 citations

Participants who received ketamine at the NIMH were among the first to receive ketamine for depression in controlled clinical trials, providing a unique opportunity to assess long-term outcomes. This analysis evaluated the relationship between participating in a ketamine clinical trial and subsequent ketamine/esketamine use after leaving the research setting. Participants seen within the NIMH...

Assessment of complement cascade components in patients with major depressive disorder.

Brain, behavior, and immunity July 1, 2025 Brandi Quintanilla, Dede Greenstein, Ashutosh Tripathi et al. 7 citations

Recent evidence suggests that the rapid-acting antidepressant ketamine has immune regulatory functions. The complement system is an important component of the innate immune response and plays a key role in synaptic plasticity. An increase in complement component 3 (C3) expression was previously found in the prefrontal cortex of individuals with depression. Given the complement system's role in...

Ketamine in clinical practice: transitioning from anesthetic agent to psychiatric therapeutic.

CNS Spectrums June 30, 2025 Jose-Manuel Quintero, Rosa-Helena Bustos, Sharon Lechtig-Wassermann et al. 6 citations

Ketamine, originally synthesized in 1962, has gained increasing attention due to its rapid and sustained antidepressant effects in treatment-resistant depression (TRD). Unlike traditional antidepressants, ketamine acts on multiple neurotransmitter systems, including NMDA receptor antagonism and AMPA receptor potentiation, offering a novel mechanism for mood regulation. Beyond psychiatry,...

REM density predicts rapid antidepressant response to ketamine in individuals with treatment-resistant depression.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology May 1, 2025 Mina Kheirkhah, Wallace C. Duncan, Qiaoping Yuan et al. 6 citations

Abnormalities during rapid eye movement (REM) sleep contribute to the pathophysiology of major depressive disorder (MDD), but few studies have explored the relationship between REM sleep and treatment-resistant depression (TRD). In MDD, REM sleep abnormalities often manifest as alterations in total night REM Density (RD), RD in the first REM period (RD1), and REM Latency (RL). Among these, RD1...

Clinical indicators of the suicide crisis and response to ketamine.

Journal of Affective Disorders March 1, 2025 Elizabeth D. Ballard, Lucinda Neely, Laura Waldman et al. 4 citations

This analysis sought to identify potential clinical targets for the suicide crisis. Characteristics of a useful clinical target include elevation at the time of suicide crisis and responsiveness to rapid-acting interventions. Suicidal ideation (SI), depression, and hopelessness were hypothesized to meet these criteria. Participants were 118 adults across the continuum of suicide risk, including...

Response of iPSC-derived neurons from individuals with treatment-resistant depression to (2 R,6 R)-hydroxynorketamine and reelin: an exploratory study.

Translational Psychiatry November 18, 2025 Jenessa N Johnston, Peixiong Yuan, Bashkim Kadriu et al. 2 citations

Treatment-resistant depression (TRD) is associated with worse clinical outcomes and longer course of illness. However, TRD is more difficult to model in animal phenotypes, suggesting that other experimental and translational models must be considered to properly address and research novel therapeutics. Reelin, an endogenous glycoprotein downregulated in depression, has shown rapid...

Can ketamine and other glutamate receptor modulators be considered entactogens?

Psychiatry Research July 1, 2025 Hiroe Hu, Alaina N Tillman, Miyu Fujita et al. 2 citations

Subanesthetic-dose ketamine has recently been reported to improve hedonic pleasures associated with social interactions and altruism in individuals with treatment-resistant depression. However, whether ketamine-among other glutamate receptor modulators-also improves empathy and/or prosocial behavior in humans remains unknown. Under a framework grounded in neurobiology that proposes that...

Ketamine's Influence on Magnetoencephalography Patterns During a Working Memory Task in Treatment-Resistant Depression: An Exploratory Study.

Bipolar Disorders April 2, 2025 Adam Fijtman, Mani Yavi, Abigail Vogeley et al. 2 citations

Treatment-resistant depression (TRD) remains a challenge, necessitating novel interventions that address associated cognitive deficits. The glutamatergic modulator ketamine exerts rapid antidepressant effects, prompting investigators to assess its impact on cognitive function, specifically working memory. This study explored ketamine's influence on working memory and magnetoencephalography...

Ketamine rescues anhedonia by cell-type and input specific adaptations in the Nucleus Accumbens

bioRxiv Preprint Server June 8, 2023 Federica Lucantonio, Shuwen Li, Jaden Lu et al. 2 citations preprint

Ketamine’s role in providing a rapid and sustained antidepressant response, particularly for patients unresponsive to conventional treatments, is increasingly recognized. A core symptom of depression, anhedonia, or the loss of enjoyment or interest in previously pleasurable activities, is known to be significantly alleviated by ketamine. While several hypotheses have been proposed regarding the...

Ketamine Infusions and Rapid Reduction of Suicidal and Depressive Symptoms in Major Depressive Episode: A Systematic Review and Meta-Analysis.

JAMA Psychiatry July 1, 2026 Sung Ryul Shim, Hye Su Jeong, Tanner J. Bommersbach et al. 1 citation

While intravenous ketamine is not approved by the US Food and Drug Administration, it is increasingly used with off-label indications as a novel treatment for suicidal and depressive symptoms. To systematically review and metasynthesize the efficacy and safety data for intravenous ketamine in treating major depressive episodes (MDEs). PubMed, PsycInfo, Cochrane Library, and Embase were...

Advancing cancer neuroscience through stress modulation: Interdisciplinary potential of psilocybin and ketamine

General Hospital Psychiatry February 25, 2026 Alan C. Courtes, Blake Myers, Noah Daly et al. 1 citation

Psychological stress not only undermines quality of life for people with cancer but also fuels tumor growth. Emerging evidence from the nascent field of cancer neuroscience suggests that adrenergic signaling from direct tumor-neuron interactions drives cancer progression, resistance to treatment, and worse outcomes. Cancer neuroscientists are increasingly seeking to repurpose psychoactive...

Blunted arginine vasopressin secretion in individuals experiencing a major depressive episode with comorbid post-traumatic stress disorder: Results from an exploratory study using copeptin as a surrogate marker.

Journal of Neuroendocrinology January 1, 2026 Hiroe Hu, Yoojin Lee, Alaina N Tillman et al. 1 citation

Arginine vasopressin (AVP) modulates stress responsivity and social-affective behaviors, but its role in mood and trauma-related disorders remains poorly defined due to challenges in peripheral measurement. This study used copeptin, a stable, reliable, and well-validated surrogate marker of AVP secretion, to assess vasopressinergic function in a transdiagnostic sample of individuals...