Review
Neurosciences
Jenessa N. N. Johnston, Bashkim Kadriu, Christoph Kraus, Ioline D. D. Henter, Carlos A. A. Zarate
Summary: The discovery of ketamine as a rapid-acting antidepressant has revolutionized neuropsychiatric therapeutics, providing a new approach to treating various disorders within hours or days. Subanesthetic-dose ketamine, along with its (S)-enantiomer esketamine, has shown promise in treating depression, bipolar disorder, anxiety spectrum disorders, substance use disorders, eating disorders, and chronic pain. Furthermore, ketamine effectively targets symptoms associated with multiple disorders, such as anxiety, anhedonia, and suicidal ideation. This manuscript reviews the pharmacology and mechanisms of ketamine in clinical research, compares the efficacy of different ketamine variants, discusses its daily use in clinical settings, explores its applications in other psychiatric disorders and comorbidities, and provides insights from the study of other novel therapeutics and neuroimaging modalities.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Neurosciences
Jenessa N. Johnston, Bashkim Kadriu, Josh Allen, Jessica R. Gilbert, Ioline D. Henter, Carlos A. Zarate
Summary: The discovery of ketamine as a rapid-acting antidepressant has led to significant research on its mechanisms of action and identification of other similar compounds. Serotonergic psychedelics (SPs) have shown potential in treating depression, but conducting controlled trials and long-term clinical observation pose challenges. This review compares the psychoactive effects and mechanisms of action of ketamine and SPs and highlights their similarities in downstream mechanisms, such as mTORC1 signaling and GABAA receptor activity. However, research on SPs is still in its early stages compared to ketamine.
Article
Psychiatry
Ana Paula Anzolin, Jeferson Ferraz Goularte, Jairo Vinicius Pinto, Paulo Belmonte-de-Abreu, Luciane Nascimento Cruz, Victor Hugo Schaly Cordova, Lucas Sueti Magalhaes, Adriane R. Rosa, Keila Maria Cereser, Marcia Kauer-Sant'Anna
Summary: This study aims to assess the control effect of ketamine on suicidal ideation and behavior in patients with depressive episodes, as well as its impact on psychopathology and inflammatory biomarkers.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Clinical Neurology
Melody J. Y. Kang, Gustavo H. Vazquez
Summary: This study evaluated the efficacy of acute intravenous ketamine treatment for treatment-resistant depression (TRD) and explored the peripheral blood-based biomarkers associated with treatment response. The results showed that ketamine significantly improved depressive symptoms and was well tolerated. In addition, baseline BDNF levels were found to be predictive of treatment response to ketamine.
JOURNAL OF AFFECTIVE DISORDERS
(2022)
Article
Neurosciences
Yu-Jung Cheng, Chieh-Hsin Lin, Hsien-Yuan Lane
Summary: Sarcosine, benzoate, and ketamine have been shown to have therapeutic effects on depression by modulating NMDA receptors and reducing brain inflammation. They exert their anti-inflammatory effects by inhibiting microglial activity, and have demonstrated efficacy in animal models or human trials.
Article
Psychiatry
Tuyen T. Le, Joshua D. Di Vincenzo, Kayla M. Teopiz, Yena Lee, Danielle S. Cha, Leanna M. W. Lui, Nelson B. Rodrigues, Roger C. Ho, Bing Cao, Kangguang Lin, Flora Nasri, Hartej Gill, Orly Lipsitz, Mehala Subramaniapillai, Rodrigo B. Mansur, Joshua D. Rosenblat, Roger S. McIntyre
Summary: Psychotic depression is a severe subtype of major depressive disorder with high relapse and mortality rates. Ketamine may be an alternative pharmacotherapy, but its efficacy and safety in patients with psychotic depression have not been established.
PSYCHIATRY RESEARCH
(2021)
Review
Clinical Neurology
Jolien K. E. Veraart, Sanne Y. Smith-Apeldoorn, Harm-Pieter Spaans, Jeanine Kamphuis, Robert A. Schoevers
Summary: Studies suggest that ketamine treatment may provide faster but possibly less durable antidepressant effects compared to ECT, with less cognitive impairment as a potential advantage. Methodologically well-designed studies with larger sample sizes and longer follow-up durations are needed to further evaluate the efficacy and safety of ketamine as an alternative treatment for patients with TRD.
JOURNAL OF AFFECTIVE DISORDERS
(2021)
Review
Pharmacology & Pharmacy
Farhan Fancy, Sipan Haikazian, Danica E. Johnson, David C. J. Chen-Li, Anastasia Levinta, Muhammad I. Husain, Rodrigo B. Mansur, Joshua D. Rosenblat
Summary: This systematic review summarizes the efficacy, safety, and tolerability of ketamine in treating bipolar depression. Preliminary evidence suggests that intravenous ketamine is safe and effective for the treatment of bipolar depression.
THERAPEUTIC ADVANCES IN PSYCHOPHARMACOLOGY
(2023)
Article
Clinical Neurology
David S. Mathai, Scott M. Lee, Victoria Mora, Kelley C. O'Donnell, Albert Garcia-Romeu, Eric A. Storch
Summary: This study examined informed consent documents from a convenience sample of 23 outpatient ketamine clinics in the United States. The findings showed that improvements are needed in addressing long-term adverse effects, treatment alternatives, medical/psychiatric evaluations prior to treatment, medical/psychological support during treatment, adjunctive psychological interventions, and subjective/dissociative-type effects. Additionally, all forms had poor readability.
JOURNAL OF AFFECTIVE DISORDERS
(2022)
Article
Psychiatry
Nicolas Garel, Jessica Drury, Julien Thibault Levesque, Nathalie Goyette, Alexandre Lehmann, Karl Looper, David Erritzoe, Shannon Dames, Gustavo Turecki, Soham Rej, Stephane Richard-Devantoy, Kyle T. Greenway
Summary: This article presents the Montreal model, a comprehensive biopsychosocial approach to ketamine for severe treatment-resistant depression (TRD). The model aims to bridge the gap between biomedical and psychedelic treatments and provides a feasible, flexible, and standardized approach to ketamine for TRD.
FRONTIERS IN PSYCHIATRY
(2023)
Review
Pharmacology & Pharmacy
Jamie L. Tully, Amelia D. Dahlen, Connor J. Haggarty, Helgi B. Schioth, Samantha Brooks
Summary: There is a growing interest in the psychiatric properties of ketamine, a dissociative anaesthetic, due to its fast-acting mood-enhancing and anxiolytic effects. These effects persist even after the main psychoactive symptoms have diminished, making ketamine a potential treatment for refractory anxiety disorders. Ketamine acts as a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) glutamate receptor, which is responsible for its pain relief and anaesthetic effects. However, the role of NMDA receptors in anxiety reduction is still not well understood. This systematic review examines the evidence of ketamine's significant reduction of refractory anxiety and discusses the possible involvement of NMDA receptor antagonism and other receptors. The review also highlights the temporary nature of the anxiolytic effects and the discrepancies in study designs regarding administration routes, complementary treatments, and other factors.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Review
Behavioral Sciences
Stephen D. Worrell, Thomas J. Gould
Summary: Excessive alcohol consumption in the US contributes to a significant number of deaths and financial burden each year. The complexity of Alcohol Use Disorder (AUD) involves neurotransmitter systems, synaptic plasticity, neurogenesis, and neural connectivity. Depressed mood and stress play crucial roles in AUD relapse, with comorbidity between AUD, depression, and stress disorders suggesting potential overlap in treatment approaches. Current pharmacotherapies for AUD have limitations, indicating the need for novel therapeutics like ketamine, which has shown promise in treating AUD, depression, and stress disorders.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Review
Psychiatry
Shakila Meshkat, Sipan Haikazian, Joshua D. Di Vincenzo, Farhan Fancy, Danica Johnson, David Chen-Li, Roger S. McIntyre, Rodrigo Mansur, Joshua D. Rosenblat
Summary: This systematic review evaluates the efficacy, tolerability, and safety of oral ketamine, esketamine, and r-ketamine for unipolar and bipolar depression. The results indicate significant antidepressant effects and good tolerability of oral ketamine. However, the included randomized controlled trials had a high risk of bias, and further research with larger sample sizes and longer follow-up periods is needed to determine the antisuicidal effects and efficacy in treatment-resistant depression.
WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY
(2023)
Article
Chemistry, Multidisciplinary
Lige Leng, Kai Zhuang, Hui Lin, Jinjun Ding, Shangchen Yang, Ziqi Yuan, Changquan Huang, Guimiao Chen, Zhenlei Chen, Mengdan Wang, Han Wang, Hao Sun, Huifang Li, He Chang, Zhenyi Chen, Qi Xu, Tifei Yuan, Jie Zhang
Summary: This study demonstrates the critical role of Menin in depression and proves that Menin is key to the antidepressant function of ketamine. Dysregulation of PV levels is closely associated with depression, and Menin stabilizes PV levels in a PKA-dependent manner.
Review
Clinical Neurology
Anees Bahji, Carlos A. Zarate, Gustavo H. Vazquez
Summary: This study reviewed 6 experimental studies on the use of ketamine for treating bipolar depression and found a higher response rate in patients receiving ketamine compared to those receiving a placebo, with reasonable tolerability. However, further research is needed to explore longer-term outcomes and alternative formulations of ketamine.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Psychiatry
Flurin Cathomas, Laura Bevilacqua, Aarthi Ramakrishnan, Hope Kronman, Sara Costi, Molly Schneider, Kenny L. Chan, Long Li, Eric J. Nestler, Li Shen, Dennis S. Charney, Scott J. Russo, James W. Murrough
Summary: Ketamine has rapid and sustained antidepressant effects in treatment-resistant depression (TRD) patients, although the underlying mechanisms are still unclear. This study found that TRD patients had a gene expression pattern indicative of interferon signaling pathway activation at baseline, and responders to ketamine treatment showed differential gene expression compared to non-responders. However, no gene expression changes related to an anti-inflammatory effect were observed.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Immunology
Sarah Boukezzi, Sara Costi, Lisa M. Shin, Seunghee Kim-Schulze, Flurin Cathomas, Abigail Collins, Scott J. Russo, Laurel S. Morris, James W. Murrough
Summary: This study found that patients with depression showed heightened neural response to threat, and it was correlated with inflammatory response and anxious arousal. The findings suggest that inflammation and amygdala activation may partially mediate the effect of stress on anxious arousal.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Clinical Neurology
Sara Costi, Ming-Hu Han, James W. Murrough
Summary: Modulators of KCNQ voltage-gated potassium channels may have antidepressant potential by regulating neuronal excitability and activity. Initial studies in animal models and clinical trials have shown the antidepressant efficacy of KCNQ2/3 channel openers.
Article
Ophthalmology
Yi Zhou, James Murrough, Yinxi Yu, Neeta Roy, Rony Sayegh, Penny Asbell, Maureen G. Maguire, Gui-Shuang Ying
Summary: Depression is associated with more severe symptoms and signs of dry eye disease, suggesting that depression should be considered as a comorbidity in the management of patients with dry eye disease.
JAMA OPHTHALMOLOGY
(2022)
Article
Psychiatry
Yael Jacob, Laurel S. Morris, Gaurav Verma, Sarah B. Rutter, Priti Balchandani, James W. Murrough
Summary: The hippocampus and amygdala limbic structures play a critical role in the development of major depressive disorder (MDD). This study explores the role of their subregions in the whole brain network to uncover patterns related to the disorder. The results suggest that alterations in the connectivity and clustering of these subregions are associated with the diagnosis and severity of depression.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Clinical Neurology
Adam Bayes, Brooke Short, Carlos A. Zarate, Lawrence Park, James W. Murrough, Declan M. McLoughlin, Patricio Riva-Posse, Robert Schoevers, Jolien Veraart, Sagar Parikh, Paul Glue, Johnson Fam, Rupert McShane, Veronica Galvez, Donel Martin, Phern-Chern Tor, Andre R. Brunoni, Colleen K. Loo
Summary: The safety monitoring of ketamine and esketamine presents knowledge gaps, with no standard monitoring for off-label generic ketamine and varying regulations for intranasal esketamine. The Ketamine Side Effect Tool (KSET) is recommended for comprehensive safety monitoring of acute and longer term side effects.
JOURNAL OF AFFECTIVE DISORDERS
(2022)
Article
Psychiatry
Lorig Kachadourian, James Murrough, Carly Kaplan, Sabrina Kaplan, Jordyn Feingold, Adriana Feder, Dennis Charney, Steven Southwick, Lauren Peccoralo, Jonathan DePierro, Jonathan Ripp, Robert Pietrzak
Summary: This study examined the association between acute COVID-19-related PTSD, MDD, and GAD symptoms and burnout and functional difficulties in frontline healthcare workers. The results suggest that early interventions targeting transdiagnostic symptoms of MDD, PTSD, and GAD may help mitigate the risk of burnout and functional difficulties in this population.
JOURNAL OF PSYCHIATRIC RESEARCH
(2022)
Article
Psychiatry
Judy Alper, Rui Feng, Gaurav Verma, Sarah Rutter, Kuang-han Huang, Long Xie, Paul Yushkevich, Yael Jacob, Stephanie Brown, Marin Kautz, Molly Schneider, Hung-Mo Lin, Lazar Fleysher, Bradley N. Delman, Patrick R. Hof, James W. Murrough, Priti Balchandani
Summary: This study aimed to assess volumetric differences in hippocampal subfields between patients with major depressive disorder (MDD), treatment-resistant depression (TRD) and healthy controls (HC) using high-resolution MRI data. The results showed that MDD and TRD patients had reduced volume in the right-hemisphere CA2/3 subfield compared to HC. Negative correlations between subfield volumes and life-stressor checklist scores were also found. This study provides valuable insights into the pathophysiology of depression.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Neurosciences
Sara Costi, Audrey Evers, Manish K. Jha, Matthew Klein, Jessica R. Overbey, Ki A. Goosens, JoColl Burgess, Kelvin Alvarez, Adriana Feder, Dennis S. Charney, James W. Murrough
Summary: Stress exposure is a key risk factor for the development of major depressive disorder and posttraumatic stress disorder. Enhancing stress resilience in at-risk populations could potentially protect against stress-induced disorders. The administration of ketamine one week prior to an acute stressor prevents the development of stress-induced depressive-like behavior in rodents. This study aimed to test if the prophylactic effect of ketamine against stress also applies to humans.
NEUROBIOLOGY OF STRESS
(2023)
Meeting Abstract
Neurosciences
Benedetta Bigio, Olivia Barnhill, Paolo de Angelis, Josh Dobbin, Katie Watson Lin, Marin Kautz, Natalie Rasgon, James Murrough, Bruce McEwen, Carla Nasca
NEUROPSYCHOPHARMACOLOGY
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
Charbel Gharios, Sarah Boukezzi, Lisa Shin, James Murrough, Helena Chang, Ming Yin Y. Lun, Mandy van Leent, Michael Osborne, Ahmed A. Tawakol, Zahi A. Fayad
Meeting Abstract
Neurosciences
Orna Issler, Yentl Y. van der Zee, Chunfeng Tan, Junshi Wang, Aarthi Ramakrishnan, Benoit Labonte, Carol A. Tamminga, Yan Dong, James W. Murrough, Li Shen, Eric J. Nestler
JOURNAL OF PSYCHIATRY & NEUROSCIENCE
(2022)
Letter
Psychiatry
Audrey Evers, Matthew Klein, Amy Aloysi, James Murrough, Manish K. Jha
ANNALS OF CLINICAL PSYCHIATRY
(2022)
Meeting Abstract
Neurosciences
Benedetta Bigio, Olivia Barnhill, Josh Dobbin, Paolo de Angelis, Marin Kautz, Francis Lee, James Murrough, Natalie Rasgon, Carla Nasca
BIOLOGICAL PSYCHIATRY
(2022)
Meeting Abstract
Neurosciences
Yael Jacob, Gaurav Verma, Sarah Rutter, Laurel Morris, Priti Balchandani, James Murrough
BIOLOGICAL PSYCHIATRY
(2022)
Review
Neurosciences
Maya Jammoul, Dareen Jammoul, Kevin K. Wang, Firas Kobeissy, Ralph G. Depalma
Summary: This article reviews the possible mechanisms by which traumatic brain injury (TBI) may stimulate the development of opioid use disorder (OUD) and discusses the interaction between these two processes. CNS damage due to TBI appears to drive adverse effects of subsequent OUD, with pain being a risk factor for opioid use after TBI.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Danusa Mar Arcego, Jan-Paul Buschdorf, Nicholas O'Toole, Zihan Wang, Barbara Barth, Irina Pokhvisneva, Nirmala Arul Rayan, Sachin Patel, Euclides Jose de Mendonca Filho, Patrick Lee, Jennifer Tan, Ming Xuan Koh, Chu Ming Sim, Carine Parent, Randriely Merscher Sobreira de Lima, Andrew Clappison, Kieran J. O'Donnell, Carla Dalmaz, Janine Arloth, Nadine Provencal, Elisabeth B. Binder, Josie Diorio, Patricia Pelufo Silveira, Michael J. Meaney
Summary: This study investigates the impact of environmental influences on mental health by integrating transcriptomic data from animal models with human data. The results suggest that hippocampal glucocorticoid-related transcriptional activity mediates the effects of early adversity on neural mechanisms implicated in psychiatric disorders.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Milenna T. van Dijk, Ardesheer Talati, Pratik Kashyap, Karan Desai, Nora C. Kelsall, Marc J. Gameroff, Natalie Aw, Eyal Abraham, Breda Cullen, Jiook Cha, Christoph Anacker, Myrna M. Weissman, Jonathan Posner
Summary: This study found that maternal stress is associated with future depressive symptoms and alterations in microstructure of the dentate gyrus (DG) in offspring. These results were consistent across two independent cohorts.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Josephine C. McGowan, Liliana R. Ladner, Claire X. Shubeck, Juliana Tapia, Christina T. LaGamma, Amanda Anqueira-Gonzalez, Ariana DeFrancesco, Briana K. Chen, Holly C. Hunsberger, Ezra J. Sydnor, Ryan W. Logan, Tzong-Shiue Yu, Steven G. Kernie, Christine A. Denny
Summary: Traumatic brain injury (TBI) leads to fear generalization by altering fear memory traces, and this symptom can be improved with (R,S)-ketamine.
BIOLOGICAL PSYCHIATRY
(2024)
