Journal of Neuroscience
January 3, 2023
Panos Zanos, Kyle A Brown, Polymnia Georgiou et al.
109 citations
Ketamine is a well-characterized NMDA receptor (NMDAR) antagonist, although the relevance of this pharmacology to its rapid (within hours of administration) antidepressant actions, which depend on mechanisms convergent with strengthening of excitatory synapses, is unclear. Activation of synaptic NMDARs is necessary for the induction of canonical long-term potentiation (LTP) leading to a...
Progress in Brain Research
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...
Molecular Psychiatry
September 7, 2022
Rebecca B Price, Nicholas Kissel, Andrew Baumeister et al.
80 citations
Abstract Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar...
Nature Neuroscience
August 30, 2022
Polymnia Georgiou, Panos Zanos, Ta-Chung M. Mou et al.
We show that the sex of human experimenters affects mouse behaviors and responses following administration of the rapid-acting antidepressant ketamine and its bioactive metabolite (2R,6R)-hydroxynorketamine. Mice showed aversion to the scent of male experimenters, preference for the scent of female experimenters and increased stress susceptibility when handled by male experimenters. This...
Psychopharmacology
July 2022
Hildegard A Wulf, Caroline A Browne, Carlos A. Zarate et al.
Emerging evidence has implicated the endogenous opioid system in mediating ketamine's antidepressant activity in subjects with major depressive disorder. To date, mu opioid receptors have been suggested as the primary opioid receptor of interest. However, this hypothesis relies primarily on observations that the opioid antagonist naltrexone blocked the effects of ketamine in humans and rodents....
Molecular Psychiatry
June 27, 2022
Gustavo C Medeiros, T. Gould, W. Prueitt et al.
(R,S)-ketamine (ketamine) and its enantiomer (S)-ketamine (esketamine) can produce rapid and substantial antidepressant effects. However, individual response to ketamine/esketamine is variable, and there are no well-accepted methods to differentiate persons who are more likely to benefit. Numerous potential peripheral biomarkers have been reported, but their current utility is unclear. We...
Frontiers in Molecular Neuroscience
May 30, 2022
Jenny J. Kim, M. Sapio, Fernando A. Vazquez et al.
Ketamine, an N-methyl-D-aspartate (NMDA)-receptor antagonist, is a recently revitalized treatment for pain and depression, yet its actions at the molecular level remain incompletely defined. In this molecular-pharmacological investigation in the rat, we used short- and longer-term infusions of high dose ketamine to stimulate neuronal transcription processes. We hypothesized that a progressively...
Translational Psychiatry
May 2, 2022
Ruin Moaddel, Panos Zanos, Cristan A Farmer et al.
32 citations
Abstract Subanesthetic-dose racemic ( R,S )-ketamine (ketamine) produces rapid, robust, and sustained antidepressant effects in major depressive disorder (MDD) and bipolar disorder (BD) and has also been shown to effectively treat neuropathic pain, complex regional pain syndrome, and post-traumatic stress disorder (PTSD). However, to date, its mechanism of action remains unclear. Preclinical...
Neurobiology of Stress
April 20, 2022
Steven J. Lamontagne, Elizabeth D. Ballard, Carlos A. Zarate
8 citations
Suicide is a leading cause of death and morbidity worldwide, yet few interventions are available to mitigate its risk. Barriers to effective treatments involve a limited understanding of factors that predict the onset of suicidal thoughts and behaviors. In the context of suicide risk, stress is a precipitating factor that is largely overlooked in the literature. Indeed, the pathophysiology of...
Discover Mental Health
April 15, 2022
Mani Yavi, Holim Lee, Ioline D. Henter et al.
150 citations
-enantiomer, intranasal esketamine, for the treatment of major depressive disorder (MDD). Initial studies found that a single subanesthetic-dose IV ketamine infusion rapidly (within one day) improved depressive symptoms in individuals with MDD and bipolar depression, with antidepressant effects lasting three to seven days. In 2019, esketamine received FDA approval as an adjunctive treatment for...
Current Topics in Behavioral Neurosciences
March 22, 2022
Marina Kojić, Johan Saelens, Bashkim Kadriu et al.
11 citations
The approval of ketamine for treatment-resistant depression has created a model for a novel class of rapid-acting glutamatergic antidepressants. Recent research into other novel rapid-acting antidepressants – most notably serotonergic psychedelics (SPs) – has also proven promising. Presently, the mechanisms of action of these substances are under investigation to improve these novel treatments,...
Expert Opinion on Drug Safety
March 9, 2022
Anees Bahji, Carlos A. Zarate, Gustavo Vazquez
71 citations
ABSTRACT Background Racemic ketamine and esketamine have demonstrated rapid antidepressant effects. We aimed to review the efficacy and safety of racemic and esketamine for depression. Research design and methods We conducted a PRISMA-guided review for relevant randomized controlled trials of racemic or esketamine for unipolar or bipolar major depression from database inception through 2021. We...
CNS Drugs
May 1, 2021
Ioline D. Henter, Lawrence T. Park, Carlos A. Zarate
The efficacy of standard antidepressants is limited for many patients with mood disorders such as major depressive disorder (MDD) and bipolar depression, underscoring the urgent need to develop novel therapeutics. Both clinical and preclinical studies have implicated glutamatergic system dysfunction in the pathophysiology of mood disorders. In particular, rapid reductions in depressive symptoms...
The International Journal of Neuropsychopharmacology
April 30, 2021
Anees Bahji, Carlos A. Zarate, Gustavo Vazquez
62 citations
Abstract Background Ketamine appears to have a therapeutic role in certain mental disorders, most notably unipolar major depressive disorder. However, its efficacy in bipolar depression is less clear. This study aimed to assess the efficacy and tolerability of ketamine for bipolar depression. Methods We conducted a systematic review of experimental studies using ketamine for the treatment of...
Molecular Psychiatry
April 15, 2021
Jordi Bonaventura, Sherry Lam, Meghan L. Carlton et al.
266 citations
Ketamine, a racemic mixture of (S)-ketamine and (R)-ketamine enantiomers, has been used as an anesthetic, analgesic and more recently, as an antidepressant. However, ketamine has known abuse liability (the tendency of a drug to be used in non-medical situations due to its psychoactive effects), which raises concerns for its therapeutic use. (S)-ketamine was recently approved by the United...
American Journal of Psychiatry
March 17, 2021
Roger S McIntyre, Joshua D. Rosenblat, Charles B. Nemeroff et al.
694 citations
Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based antidepressants in major depression, the majority of treated individuals fail to achieve full syndromal and functional recovery with the index and subsequent pharmacological treatments. Ketamine and esketamine represent...
medRxiv Preprint Server
February 22, 2021
Jessica R. Gilbert, Christina S. Galiano, Allison C. Nugent et al.
preprint
The glutamatergic modulator ketamine rapidly reduces depressive symptoms in individuals with treatment-resistant major depressive disorder (MDD) and bipolar disorder. While its underlying mechanism of antidepressant action is not fully understood, modulating glutamatergically-mediated connectivity appears to be a critical component moderating antidepressant response. This double-blind,...
Nature Communications
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...
The International Journal of Neuropsychopharmacology
November 16, 2020
Bashkim Kadriu, Maximillian Greenwald, Ioline D. Henter et al.
98 citations
BACKGROUND: The glutamatergic modulator ketamine has created a blueprint for studying novel pharmaceuticals in the field. Recent studies suggest that "classic" serotonergic psychedelics (SPs) may also have antidepressant efficacy. Both ketamine and SPs appear to produce rapid, sustained antidepressant effects after a transient psychoactive period. METHODS: This review summarizes areas of...
Journal of Affective Disorders
September 23, 2020
Anees Bahji, Gustavo Vazquez, Carlos A. Zarate
404 citations
Background: Ketamine appears to have a therapeutic role in certain mental disorders, most notably depression. However, the comparative performance of different formulations of ketamine is less clear. Objectives: This study aimed to assess the comparative efficacy and tolerability of racemic and esketamine for the treatment of unipolar and bipolar major depression. Design: Systematic review and...
Molecular Psychiatry
September 14, 2020
A. Mkrtchian, Jennifer W. Evans, Christoph Kraus et al.
110 citations
Ketamine improves motivation-related symptoms in depression but simultaneously elicits similar symptoms in healthy individuals, suggesting that it might have different effects in health and disease. This study examined whether ketamine affects the brain’s fronto-striatal system, which is known to drive motivational behavior. The study also assessed whether inflammatory mechanisms—which are...
Acta Psychiatrica Scandinavica
July 17, 2020
Lawrence T. Park, David A. Luckenbaugh, Steven Pennybaker et al.
23 citations
OBJECTIVE: Ketamine's effects on different dimensions of depressive symptomatology, including typical/melancholic and atypical depression, remain largely unknown. This study examined the effects of a single intravenous dose of ketamine on general depressive symptoms (measured using the Montgomery-Asberg Depression Rating Scale (MADRS), typical/melancholic symptoms (measured using the MADRS5),...
Advances in pharmacology (San Diego, Calif.)
2020
Bashkim Kadriu, Elizabeth D. Ballard, Ioline D. Henter et al.
35 citations
As a field, psychiatry is undergoing an exciting paradigm shift toward early identification and intervention that will likely minimize both the burden associated with severe mental illnesses as well as their duration. In this context, the rapid-acting antidepressant ketamine has revolutionized our understanding of antidepressant response and greatly expanded the pharmacologic armamentarium for...
Proceedings of the National Academy of Sciences
March 13, 2019
Panos Zanos, Jaclyn N. Highland, Brent W. Stewart et al.
153 citations
Significance Despite available medications for depression, currently approved antidepressants take months to exert therapeutic effects, and ∼30% of patients remain treatment resistant. In contrast, a single subanesthetic dose of ketamine exerts rapid (within hours) and sustained antidepressant actions. Preclinical studies indicate that the ketamine metabolite ( 2R , 6R )-hydroxynorketamine [(...
Proceedings of the National Academy of Sciences
February 22, 2019
E. Lumsden, Timothy A. Troppoli, S. J. Myers et al.
159 citations
Significance Standard antidepressant treatments require weeks to show effectiveness. A single subanesthetic dose of ketamine rapidly attenuates many clinical signs and symptoms of depression; however, ketamine treatment also has many adverse effects, including dissociation and potential for abuse, which are mediated by NMDA glutamate receptor (NMDAR) inhibition. Previous work has revealed that...