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Ketamine and depression

Kathryn R Cullen, Palistha Amatya, Mark G Roback, Christina Sophia Albott, Melinda Westlund Schreiner, Yanan Ren, Lynn E Eberly, Patricia Carstedt, Ali Samikoglu, Meredith Gunlicks-Stoessel, Kristina Reigstad, Nathan Horek, Susannah Tye, Kelvin O Lim, Bonnie Klimes-Dougan
BACKGROUND: Novel interventions for treatment-resistant depression (TRD) in adolescents are urgently needed. Ketamine has been studied in adults with TRD, but little information is available for adolescents. This study investigated efficacy and tolerability of intravenous ketamine in adolescents with TRD, and explored clinical response predictors. METHODS: Adolescents, 12-18 years of age, with TRD (failure to respond to two previous antidepressant trials) were administered six ketamine (0...
July 13, 2018: Journal of Child and Adolescent Psychopharmacology
Chittaranjan Andrade
No abstract text is available yet for this article.
July 11, 2018: Journal of Neurosurgical Anesthesiology
Martin Soehle, Janina Bochem
PURPOSE OF REVIEW: Electroconvulsive therapy (ECT) is a well established and effective therapy in treatment-resistant depression. It is performed under general anesthesia, but no consensus exists regarding the optimal anesthetic drugs. A growing interest in optimizing adjunctive medication regimes in ECT anesthesia has emerged in recent years. Moreover different methods of seizure induction have been evaluated. RECENT FINDINGS: Pretreatment with dexmedetomidine eased the propofol injection pain and reduced the hyperdynamic response to ECT, but prolonged recovery...
July 9, 2018: Current Opinion in Anaesthesiology
Lu Chen, Yong Gong, Rhys Salter
Ketamine is a well-known general anesthetic that inhibits cerebral NMDA receptors. Norketamine is a major circulating metabolite of this drug. A nasal spray formulation of esketamine, the S enantiomer of ketamine is under development for the management of treatment resistant depression. In order to assess the pharmacokinetic properties, C-14 labeled ketamine and norketamine were prepared separately from commercially available [14 C]CuCN through a five-step sequence with the C-14 label at the quaternary carbon of the cyclohexyl ring...
July 10, 2018: Journal of Labelled Compounds & Radiopharmaceuticals
Chadi G Abdallah, Henk M De Feyter, Lynnette A Averill, Lihong Jiang, Christopher L Averill, Golam M I Chowdhury, Prerana Purohit, Robin A de Graaf, Irina Esterlis, Christoph Juchem, Brian P Pittman, John H Krystal, Douglas L Rothman, Gerard Sanacora, Graeme F Mason
The ability of ketamine administration to activate prefrontal glutamate neurotransmission is thought to be a key mechanism contributing to its transient psychotomimetic effects and its delayed and sustained antidepressant effects. Rodent studies employing carbon-13 magnetic resonance spectroscopy (13 C MRS) methods have shown ketamine and other N-methyl-D-aspartate (NMDA) receptor antagonists to transiently increase measures reflecting glutamate-glutamine cycling and glutamate neurotransmission in the frontal cortex...
June 28, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Pravin K Mishra, Arvind Kumar, Kevin L Behar, Anant B Patel
Depression is one of the most debilitating neuropsychiatric disorders. Most of the current antidepressants have long remission time and low recovery rate. The present study explores the impact of ketamine on neuronal and astroglial metabolic activity in prefrontal cortex (PFC) in a social defeat (SD) model of depression. C57BL/6 mice were subjected to a social defeat paradigm for 5 min a day for 10 consecutive days. Ketamine (10 mg/kg, intraperitoneal) was administered to mice for two consecutive days following the last defeat stress...
July 2, 2018: Journal of Neurochemistry
Li Ren, Xuechao Hao, Su Min, Jie Deng, Qibin Chen, Hengsheng Chen, Dawei Liu
Along with its outstanding antidepressant effect, electroconvulsive shock (ECS) can induce learning and memory impairment. Propofol and ketamine have shown to be useful in alleviating the learning and memory impairment. Nevertheless, the mechanism still remains unclear. This study investigated the role of NMDA receptor (NMDAR)-mediated metaplasticity in the learning and memory impairment induced by ECS, as well as the neuroprotective effect of propofol and ketamine in depressive rats. Rats received ECS or ECS under anesthetics after chronic unpredictable mild stress procedure...
June 25, 2018: Neurobiology of Learning and Memory
Dylan Chou, Hsien-Yu Peng, Tzer-Bin Lin, Cheng-Yuan Lai, Ming-Chun Hsieh, Yang-Cheng Wen, An-Sheng Lee, Hsueh-Hsiao Wang, Po-Sheng Yang, Gin-Den Chen, Yu-Cheng Ho
It has been widely reported that ketamine rescues chronic stress-induced depression-like behavior, but the underlying cellular mechanisms of the rapid antidepressant actions of ketamine remain largely unclear. Both male and female Sprague-Dawley rats were used and received modified learned helplessness paradigm to induce depression-like behavior. Depression-like behavior was assayed and manipulated using forced swim tests, sucrose preference tests and pharmacological microinjection. We conducted whole-cell patch-clamp electrophysiological recordings in the midbrain ventrolateral periaqueductal gray (vlPAG) neurons...
June 25, 2018: Neuropharmacology
Jeanette L Berton, Mabel Seto, Craig W Lindsley
Phencyclidine (PCP, "angel dust", an arylcyclohexylamine) was the first non-natural, man-made illicit drug of abuse, and was coined 'the most dangerous drug in America" in the late 1970s (amidst sensational horror stories of the drug's effects); however, few other illicit drugs have had such a significant and broad impact on society - both good and bad. Originally developed as a new class of anesthetic, PCP-derived psychosis gave way to the PCP hypothesis of schizophrenia (later coined the NMDA receptor hypofunction hypothesis or the glutamate hypothesis of schizophrenia), which continues to drive therapeutic discovery for schizophrenia today...
June 28, 2018: ACS Chemical Neuroscience
Chun Yang, Shizuka Kobayashi, Kazuhito Nakao, Chao Dong, Mei Han, Youge Qu, Qian Ren, Ji-Chun Zhang, Min Ma, Hidetoh Toki, Jun-Ichi Yamaguchi, Shigeyuki Chaki, Yukihiko Shirayama, Kazu Nakazawa, Toshiya Manabe, Kenji Hashimoto
BACKGROUND: Ketamine, an N-methyl-D-aspartate receptor antagonist, exerts robust antidepressant effects in patients with treatment-resistant depression. The precise mechanisms underlying ketamine's antidepressant actions remain unclear, although previous research suggests that alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) activation plays a role. We investigated whether (S)-norketamine and (R)-norketamine, the two main metabolites of (R,S)-ketamine, also play a significant role in ketamine's antidepressant effects and whether the effects are mediated by AMPAR...
May 14, 2018: Biological Psychiatry
Dusan Kolar
Treatment-resistant mood disorders and anxiety disorders require intensive treatment, but treatment options should balance benefits and adverse effects or other potential detrimental effects on patients, including the risk of developing prescription medication addiction. Some of the newer treatment modalities for mood and anxiety disorders may have similar properties to benzodiazepines. The goal of this review was to identify the potential for developing dependence on the novel treatment approaches to treatment-resistant depression and refractory anxiety disorders...
2018: Neuropsychiatric Disease and Treatment
Vytautas Jankauskas, Candace Necyk, James Chue, Pierre Chue
Up to 20% of depressed patients demonstrate treatment resistance to one or more adequate antidepressant trials, resulting in a disproportionately high burden of illness. Ketamine is a non-barbiturate, rapid-acting general anesthetic that has been increasingly studied in treatment resistant depression (TRD), typically at sub-anesthetic doses (0.5 mg/kg over 40 min by intravenous infusion). More recent data suggest that ketamine may improve response rates to electroconvulsive therapy (ECT) when used as an adjunct, but also as a sole agent...
2018: Neuropsychiatric Disease and Treatment
Akiko Matsui, Michihiro Morimoto, Hiroshi Suzuki, Thomas Laurent, Yoko Fujimoto, Yoshimi Inagaki
OBJECTIVES: To investigate changes in sedation practice during 2012-2015, using a large health claims database, for catheter ablation (CA), gastrointestinal endoscopic examination (EE), and surgery (ES) after dexmedetomidine (DEX) was approved for procedural sedation in 2013. We assessed the trends of sedative utilization, sedative-analgesic combinations, and, additionally, incidence of complications from 2012 to 2015. METHODS: Using the database provided by Medical Data Vision Co...
June 18, 2018: Drugs—Real World Outcomes
Mats Persson, Jan Sörensen, Björn Gerdle
Objectives The present study challenges chronic Whiplash Associated Disorders (WAD)-subjects to a pharmacological intravenous (i.v.) test with morphine, ketamine, and active placebo (midazolam). The aim was to describe the short-term responses to drugs and the assumed heterogeneity in the patterns of responses. We related the different responder groups to the results from psychometric tests. Methods The study includes 95 patients, all with chronic WAD and referred to our departments. They answered a questionnaire including the following psychometric instruments relevant for chronic pain: Beck Depression Inventory, Coping Strategies Questionnaire, Multidimensional Pain Inventory, Life Satisfaction Checklist, SF36 and EuroQol...
December 29, 2017: Scandinavian Journal of Pain
Shaina Archer, Carson Chrenek, Jennifer Swainson
BACKGROUND: Previous studies have demonstrated ketamine to have a rapid antidepressant effect in some patients with treatment-resistant depression (TRD), but the effect is unfortunately not sustained in the long term. In this study, we report on the clinical use of ongoing maintenance ketamine infusions in a group of patients with TRD, beyond an acute course of 6 to 8 ketamine infusions. METHODS: This retrospective case series reports on 11 patients with TRD who received maintenance ketamine infusions, defined as treatments beyond an initial series of up to 8 infusions...
August 2018: Journal of Clinical Psychopharmacology
Brigitte Vanle, William Olcott, Jaime Jimenez, Luma Bashmi, Itai Danovitch, Waguih William IsHak
Among patients with Parkinson's disease (PD), depression is prevalent and disabling, impacting both health outcomes and quality of life. There is a critical need for alternative pharmacological methods to treat PD depression, as mainstream antidepressant drugs are largely ineffective in this population. Currently, there are no recommendations for the optimal treatment of PD neuropsychiatric symptoms. Given the dual antidepressant and anti-dyskinetic effects of ketamine and other N-methyl-D-aspartate (NMDA) antagonists for PD, this review aims to examine the current evidence of NMDA antagonists for treating neuropsychiatric symptoms, including memantine, amantadine, ketamine, dizoclopine, and d-cycloserine...
June 15, 2018: Translational Psychiatry
Laura Baumgartner, Nicole Townsend, Katie Winkelman, Robert MacLaren
: Objective: Traditional analgesic regimens often fail to control the severe pain patients experience during burn wound care, and the drugs are frequently administered at doses that can cause oversedation and respiratory depression. Ketamine may be an ideal agent for adjunctive analgesia in such patients because of its unique mechanism of action and lack of association with respiratory depression. This study evaluated the efficacy and safety of a critical care RN-driven protocol for IV ketamine administration during burn wound care...
July 2018: American Journal of Nursing
Ronald S Duman
Therapeutic medications for the treatment of depression have serious limitations, particularly delayed onset and low rates of efficacy. However, the discovery that a single subanesthetic dose of ketamine, a glutamate NMDA receptor channel blocker, can produce a rapid (within hours) antidepressant response that is sustained (about 1 week), even in patients considered treatment-resistant, has invigorated the field. In addition to these remarkable actions, ketamine has proven effective for the treatment of suicidal ideation...
2018: F1000Research
Allie J Widman, Amy E Stewart, Elise M Erb, Elizabeth Gardner, Lori L McMahon
In the past 20 years, ketamine has become a promising treatment for Major Depressive Disorder (MDD) due to its rapid and sustain antidepressant effects in patients. A single ketamine treatment causes improvement in depressive symptoms within hours and can last weeks, long after it is eliminated. Previous studies have demonstrated increased synaptic plasticity at CA3-CA1 synapses in hippocampus (HPC) 24 h post ketamine treatment suggesting increased activity-dependent hippocampal function may underlie the antidepressant effects of ketamine...
2018: Frontiers in Synaptic Neuroscience
Calvin Ly, Alexandra C Greb, Lindsay P Cameron, Jonathan M Wong, Eden V Barragan, Paige C Wilson, Kyle F Burbach, Sina Soltanzadeh Zarandi, Alexander Sood, Michael R Paddy, Whitney C Duim, Megan Y Dennis, A Kimberley McAllister, Kassandra M Ori-McKenney, John A Gray, David E Olson
Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology...
June 12, 2018: Cell Reports
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