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Ketamine and depression

Wei Wang, Le Liu, Xiu Yang, Han Gao, Qi-Kai Tang, Luo-Yue Yin, Xiao-Yu Yin, Jing-Ru Hao, De-Qin Geng, Can Gao
Chronic stress is an important factor for depression. Most individuals recover from stress, while some develop into depression. The pathogenesis of resilience or susceptibility remains unclear. Stress activates the hypothalamic-pituitary-adrenal (HPA) axis and releases stress hormones to regulate individual response to stress. Hence, we assessed the effects of chronic social defeat stress (CSDS) on susceptible behaviors, plasma corticosterone (CORT) concentration, glucocorticoid receptor (GR) expressions in hippocampus and medial prefrontal cortex (mPFC)...
February 9, 2019: Behavioural Brain Research
Ronald S Duman
About 30 percent of all people suffering from depression do not respond adequately to available treatments. Our author, a leading researcher in the field of antidepressants, says that the rediscovery of a promising, yet problematic, drug called ketamine is the most significant breakthrough for treating depression in half a century. Will ketamine inspire the next generation of antidepressants ?
March 2018: Cerebrum: the Dana Forum on Brain Science
Kelly A Bryant, Murat Altinay, Nora Finnegan, Kim Cromer, Roman M Dale
PURPOSE: There is an immediate need for more sustainable, effective therapies for treatment-resistant depression in patients who do not respond to traditional psychopharmacology. The aim of this study was to determine the efficacy and safety of intravenous ketamine infusions on the elderly population by using a case series of 6 geriatric patients with treatment-resistant depression. METHODS: Eligible patients aged 65 to 82 were given a subanesthetic ketamine hydrochloride dose of 0...
February 7, 2019: Journal of Clinical Psychopharmacology
Agnieszka Pałucha-Poniewiera, Karolina Podkowa, Andrzej Pilc
Ketamine has been shown to induce a rapid antidepressant effect on patients with depression. In many animal models, both rapid and sustained antidepressant activities were also found in response to an antagonist of group II metabotropic glutamate receptors, LY341495, and its mechanism of action seemed to be similar in many ways to the action of ketamine. It has also been found that LY341495 enhanced the antidepressant-like activity of sub-effective doses of ketamine in rats without inducing adverse effects...
February 4, 2019: Behavioural Pharmacology
Yiu Chung Tse, Joëlle Lopez, Alexandre Moquin, Shui-Ming Alice Wong, Dusica Maysinger, Tak Pan Wong
N-methyl-D-aspartate receptors (NMDARs) have been highly implicated in the pathogenesis and treatment of depression. While NMDARs can be found inside and outside glutamate synapses, it remains unclear if NMDARs at synaptic (sNMDAR) and extrasynaptic locations (exNMDAR) play different roles in the formation of depression-related behaviors. Using chronic social defeat stress (CSDS), an animal model for anxiety- and depression-related behaviors, we found that mice susceptible to CSDS exhibited low hippocampal exNMDAR function...
January 25, 2019: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Susanne Dyal, Robert MacLaren
Background: Alcohol withdrawal occurs commonly but diagnosis and therapies have not been described. Objective: To characterize practices regarding the assessment and treatment of acute severe alcohol withdrawal and describe perceived barriers to therapies. Methods: A random sample of 500 US-based critical care pharmacists received the pretested, electronically distributed questionnaire. Results: 94 (20%) of 471 eligible recipients responded with diverse representation. Manifestations of alcohol withdrawal that were commonly rated as severe were seizures (91...
February 2019: Hospital Pharmacy
Yihui Cui, Yan Yang, Yiyan Dong, Hailan Hu
The rapid antidepressant effect of ketamine is arguably one of the most significant advances in the mental health field in the last half century. However, its mechanism of action has remained elusive. Here, we describe our latest discovery on how ketamine blocks N -methyl-D-aspartate receptor (NMDAR)-dependent burst firing of an "antireward" center in the brain, the lateral habenula (LHb), to mediate its antidepressant effects. We also discuss a novel structure-function mechanism at the glia-neuron interface to account for the enhanced LHb bursting during depression...
February 4, 2019: Cold Spring Harbor Symposia on Quantitative Biology
Lise Vlerick, Kathelijne Peremans, Robrecht Dockx, Kurt Audenaert, Chris Baeken, Jimmy H Saunders, Ingeborgh Polis
Subanaesthetic ketamine has recently been established as an effective and rapid treatment for major depressive disorder showing antidepressant effects for up to 1 week on average. The use of repeated ketamine infusions has been put forward to augment and to prolong the antidepressant response and increase the remission rates. The underlying neurobiological mechanisms responsible for ketamine's antidepressant effects remain unclear. Nevertheless, it has been shown, both in dogs and humans, that ketamine can alter neuronal perfusion and therefore neuronal function in brain regions involved in psychiatric and behavioural disorders...
January 16, 2019: Psychiatry research. Neuroimaging
Kayla A Nichols, Christopher A Paciullo
Ketamine is an anesthetic known globally both for its potent dissociative properties and potential for abuse. More recently, ketamine demonstrates utility in a variety of disease states such as treatment-resistant depression, status asthmaticus, and acute agitation. In addition, ketamine has been shown to demonstrate various effects at different doses, which adds to its pharmacological benefit. As these new indications continue to come to light, it is important to stay current with the dosing for these indications as well as the adverse effects associated with ketamine's use...
January 2019: Advanced Emergency Nursing Journal
S Alaiyed, P L Bozzelli, A Caccavano, J Y Wu, K Conant
Drugs that target monoaminergic transmission represent a first-line treatment for major depression. Though a full understanding of the mechanisms that underlie antidepressant efficacy is lacking, evidence supports a role for enhanced excitatory transmission. This can occur through two non-mutually exclusive mechanisms. The first involves increased function of excitatory neurons through relatively direct mechanisms such as enhanced dendritic arborization. Another mechanism involves reduced inhibitory function, which occurs with the rapid antidepressant ketamine...
January 30, 2019: Journal of Neurochemistry
Oliver D Robertson, Nieves G Coronado, Rickinder Sethi, Michael Berk, Seetal Dodd
AIM: Neuropsychiatric disorders including depression, bipolar and schizophrenia frequently exhibit a neuroprogressive course from prodrome to chronicity. There are a range of agents exhibiting capacity to attenuate biological mechanisms associated with neuroprogression. This review will update the evidence for putative neuroprotective agents including clinical efficacy, mechanisms of action and limitations in current assessment tools, and identify novel agents with neuroprotective potential...
January 28, 2019: Early Intervention in Psychiatry
Nikolaos Pitsikas, Georgia Georgiadou, Foteini Delis, Katerina Antoniou
There is scarce information regarding the effects of anesthetic doses of the non-competitive N-methyl-D-aspartate receptor antagonist ketamine on anxiety. The current study evaluated the acute effects of intraperitoneally (i.p.) administered anesthetic ketamine (100 mg/kg) i.p. on anxiety in rats. For this purpose, the light/dark and the open field tests were utilized. The effects of anesthetic ketamine on motility were also examined using a motility cage. In the light/dark test, anesthetic ketamine, administered 24 h before testing reduced the number of transitions between the light and dark compartments and the time spent in the light compartment in the rats compared with their control cohorts...
January 17, 2019: Neurochemical Research
Fan Zhang, Guihua Huang, Xianlin Zhu
Electroconvulsive therapy (ECT) is an efficient therapy for major depression and modern ECT requires anesthesia to enhance safety. However, the commonly used anesthetic, propofol, may weaken the treatment efficacy. A recent study confirmed that ketamine rapidly reduced the symptoms of depression in affected patients. A previous study found that electroconvulsive seizure (ECS), the animal model for ECT, under anesthesia of low-dose ketamine combined with propofol could enhance the antidepressant efficacy and improve the cognitive performance...
January 2019: Experimental and Therapeutic Medicine
Brendan D Hare, Ryota Shinohara, Rong Jian Liu, Santosh Pothula, Ralph J DiLeone, Ronald S Duman
Impaired function in the medial prefrontal cortex (mPFC) contributes to depression, and the therapeutic response produced by novel rapid-acting antidepressants such as ketamine are mediated by mPFC activity. The mPFC contains multiple types of pyramidal cells, but it is unclear whether a particular subtype mediates the rapid antidepressant actions of ketamine. Here we tested two major subtypes, Drd1 and Drd2 dopamine receptor expressing pyramidal neurons and found that activating Drd1 expressing pyramidal cells in the mPFC produces rapid and long-lasting antidepressant and anxiolytic responses...
January 15, 2019: Nature Communications
Michael P Schnetz, Harry S Hochheiser, David J Danks, Douglas P Landsittel, Keith M Vogt, James W Ibinson, Steven L Whitehurst, Sean P McDermott, Melissa Giraldo Duque, Ata M Kaynar
BACKGROUND: Mean arterial pressure (MAP), bispectral index (BIS), and minimum alveolar concentration (MAC) represent valuable, yet dynamic intraoperative monitoring variables. They provide information related to poor outcomes when considered together, however their collective behavior across time has not been characterized. METHODS: We have developed the Triple Variable Index (TVI), a composite variable representing the sum of z-scores from MAP, BIS, and MAC values that occur together during surgery...
January 14, 2019: BMC Medical Research Methodology
Marlene P Freeman, George I Papakostas, Bettina Hoeppner, Erica Mazzone, Heidi Judge, Cristina Cusin, Sanjay Mathew, Gerard Sanacora, Dan Iosifescu, Charles DeBattista, Madhukar H Trivedi, Maurizio Fava
BACKGROUND: While ketamine has been increasingly studied for treatment resistant depression (TRD), the impact of sex differences on treatment outcomes has not been well studied. The objective was to ascertain whether there were differences in response to a single administration of ketamine for TRD between men and women, and between pre- and post-menopausal women. METHODS: A randomized, double-blind, placebo-controlled trial (N = 99; N = 50 male; N = 49 female) was conducted to investigate the efficacy of intravenous ketamine versus active placebo as augmentation of antidepressant therapy for TRD...
January 8, 2019: Journal of Psychiatric Research
Jeffrey S Kroin, Vaskar Das, Mario Moric, Asokumar Buvanendran
BACKGROUND AND OBJECTIVES: Ketamine has been shown to reduce chronic pain; however, the adverse events associated with ketamine makes it challenging for use outside of the perioperative setting. The ketamine metabolite (2R,6R)-hydroxynorketamine ((2R,6R)-HNK) has a therapeutic effect in mice models of depression, with minimal side effects. The objective of this study is to determine if (2R,6R)-HNK has efficacy in both acute and chronic mouse pain models. METHODS: Mice were tested in three pain models: nerve-injury neuropathic pain, tibia fracture complex regional pain syndrome type-1 (CRPS1) pain, and plantar incision postoperative pain...
January 2019: Regional Anesthesia and Pain Medicine
M Neus Fullana, Esther Ruiz-Bronchal, Albert Ferrés-Coy, Elena Juárez-Escoto, Francesc Artigas, Analia Bortolozzi
Elevation of energy metabolism and disturbance of astrocyte number/function in the ventral anterior cingulate cortex (vACC) contributes to the pathophysiology of major depressive disorder (MDD). Functional hyperactivity of vACC may result from reduced astrocytic glutamate uptake and increased neuronal excitation. Here we tested this hypothesis by knocking-down astrocytic glutamate transporter GLAST/GLT-1 expression in mouse infralimbic (IL, rodent equivalent of vACC) or prelimbic (PrL) cortices using RNAi strategies...
January 11, 2019: Glia
David Dadiomov, Kelly Lee
Introduction: Suicidality and self-injurious behavior afflict patients with a wide variety of psychiatric illnesses. Currently, there are few pharmacologic treatments for suicidality and self-injurious behavior and none that treat these conditions emergently. Recently, ketamine has demonstrated efficacy in treating both depression and acute suicidal ideation. An increasing usage of ketamine, of a variety of formulations, has been studied for these indications. This article reviews the evidence for use of ketamine in self-injurious behavior and suicidality...
January 2019: The mental health clinician
Gihyun Yoon, Ismene L Petrakis, John H Krystal
No abstract text is available yet for this article.
January 9, 2019: JAMA Psychiatry
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