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Ketamine and depression

Maria Filip, Justyna Jasionowska, Piotr Gałecki
Depressive disorders are the most common disease entities in psychiatry. Slightly more than 50% of patients diagnosed with major depressive disorder (MDD) were treated using available antidepressants have shown the complete remission, and over 1/3 of patients have not responded to conventional treatment presenting treatment-resistant depression (TRD). Possible treatment of this type of disorder is pharmacotherapy, which in some cases turns out to be ineffective. Scientists studying this problem suggest using ketamine - a drug known for being used in anaesthesiology and intensive therapy...
September 21, 2018: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
Thomas Liebe, Meng Li, Lejla Colic, Matthias H J Munk, Catherine M Sweeney-Reed, Marie Woelfer, Moritz A Kretzschmar, Johann Steiner, Felicia von Düring, Gusalija Behnisch, Björn H Schott, Martin Walter
BACKGROUND: Ketamine is receiving increasing attention as a rapid-onset antidepressant in patients suffering from major depressive disorder (MDD) with treatment resistance or severe suicidal ideation. Ketamine modulates several neurotransmitter systems, including norepinephrine via the norepinephrine transporter (NET), both peripherally and centrally. The locus coeruleus (LC), which has high NET concentration, has been attributed to brain networks involved in depression. Thus we investigated the effects of single-dose of racemic ketamine on the LC using resting state functional MRI...
September 4, 2018: NeuroImage: Clinical
Fernanda S Correia-Melo, Gustavo C Leal, Michelle S Carvalho, Ana Paula Jesus-Nunes, Carolina B N Ferreira, Flávia Vieira, Guilherme Magnavita, Lucas A S Vale, Rodrigo P Mello, Carolina Nakahira, Felipe C Argolo, Tanise Cardoso, Cezar D S Souza, Ana Teresa C Fontes, Marcelo B Ferreira, Lucas Araújo-de-Freitas, Marco A Tuena, Mariana V F Echegaray, Diogo E Cavalcanti, Ana C Lucchese, Igor D Bandeira, Manuela Telles, Cássio S Lima, Aline S Sampaio, Samantha S Silva, Roberta F Marback, José A Del-Porto, José Neander Abreu, Luciana M Sarin, Camilla S Paixão, Lucas P Carvalho, Paulo R L Machado, Gustavo Turecki, Acioly L T Lacerda, Lucas C Quarantini
INTRODUCTION: The use of ketamine as an option in the treatment of depressive disorder is growing rapidly, supported by numerous clinical trials attesting its efficacy and safety. Esketamine, the S (+) enantiomer of ketamine, is the most widely used form in the anesthetic environment in some countries, and new studies have shown that it may also be effective in depression and with better tolerability. However, no study so far has directly compared esketamine with racemic ketamine. Here we propose a protocol of a clinical trial to evaluate esketamine as a noninferior medication when compared to ketamine in the treatment of patients with treatment-resistant depression...
September 2018: Medicine (Baltimore)
Fan Zhang, Jie Luo, Xianlin Zhu
Some studies have indicated that ketamine has a rapid antidepressant effects, but the underlying molecular mechanism is still unclear. Researchers have found that mature brain-derived neurotrophic factor (mBDNF) and its precursor proBDNF are related to depression; they elicit opposite effects on cellular functions. It is clear that tissue plasminogen activator (tPA) is a key regulatory element in the conversion of proBDNF to mBDNF. The chronic unpredicted mild stress (CUMS) procedure is a classical and reliable method to establish the model of depression...
August 20, 2018: Psychiatry Research
Kai Zhang, Hidetoh Toki, Yuko Fujita, Min Ma, Lijia Chang, Youge Qu, Shingo Harada, Tetsuhiro Nemoto, Akiko Mizuno-Yasuhira, Jun-Ichi Yamaguchi, Shigeyuki Chaki, Kenji Hashimoto
RATIONALE: (R,S)-ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, exhibits rapid and long-lasting antidepressant effects and anti-suicidal ideation in treatment-resistant patients with depression. However, the precise mechanisms underlying the antidepressant actions of (R,S)-ketamine are unknown. Although the previous report demonstrated the deuterium isotope effects in the antidepressant actions of (R,S)-ketamine, the deuterium isotope effects in the antidepressant actions of (R)-ketamine, which is more potent than (S)-ketamine, are unknown...
September 13, 2018: Psychopharmacology
Yanling Zhou, Wei Zheng, Weijian Liu, Chengyu Wang, Yanni Zhan, Hanqiu Li, Lijian Chen, Mingding Li, Yuping Ning
Ketamine has rapid antidepressant effects on treatment-resistant depression, but the biological mechanism underpinning this effect is less clear. Our aims were to examine whether kynurenine pathway metabolites were altered by six infusions of ketamine and whether these biological factors could act as potential biomarkers to predict ketamine's antidepressant effects. Six intravenous infusions of ketamine (0.5 mg/kg) were administered to 84 patients with unipolar and bipolar depression over a 12-d period. Symptom severity and response were assessed using the Montgomery-Asberg Scale (MADRS), and blood samples were collected at baseline and 24 hours following the first infusion and at 24 hours and 14 d after the sixth infusion (24 hours, 13 d and 26 d)...
September 10, 2018: Brain, Behavior, and Immunity
Maggie Williams, Nigel Caulkett, Peter Neuhaus, Kathreen Ruckstuhl, Soren Boysen, Åsa Fahlman
Chemical immobilization is a key aspect of wildlife management. To minimize dose-dependent adverse effects, immobilization protocols often include two or more synergistic agents, which allows for reductions in individual drug dosages. Free-ranging bighorn sheep ( Ovis canadensis) in Canada ( n = 74) were remotely injected with a combination of medetomidine (0.16 ± 0.04 mg/kg) and ketamine (4.0 ± 1.4 mg/kg) (MK), or combination of medetomidine (0.14 ± 0.06 mg/kg), azaperone (0.21 ± 0.11 mg/kg), and alfaxalone (0...
September 2018: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
Farzan Kheirkhah, Gooya Tayyebi, Seyed Mozaffar Rabiee, Ali-Akbar Moghadamnia, Ali Bijani
Background: Major depressive disorder is a severe, heterogeneous, common medical illness and a leading cause of disability throughout the world that poses a significant public health issue. Previous studies have shown rapid antidepressant effects following a single administration of ketamine. This study aimed to assess the impact of route of administration and dose of ketamine for the reduction of depressive symptoms and compare the effects of different doses and methods. Methods: A double-blind clinical controlled trial was done on 100 patients with a primary diagnosis of major depressive disorder who were assigned into two groups of 50 subjects at a dose of 0...
2018: Caspian Journal of Internal Medicine
Francis L Pazini, Mauricio P Cunha, Ana Lúcia S Rodrigues
Depression, a highly prevalent neuropsychiatric disorder worldwide, causes a heavy burden for the society and is associated with suicide risk. The treatment of this disorder remains a challenge, since currently available antidepressants provide a slow and, often, incomplete response and cause several side effects that contribute to diminish the adhesion of patients to treatment. In this context, several nutraceuticals have been investigated regarding their possible beneficial effects for the management of this neuropsychiatric disorder...
September 5, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Haley L Goodwill, Gabriela Manzano-Nieves, Meghan Gallo, Hye-In Lee, Esther Oyerinde, Thomas Serre, Kevin G Bath
Childhood trauma and neglect influence emotional development and increase the risk for and severity of mental illness. Women have a heightened susceptibility to the effects of early life stress (ELS) and are twice as likely as men to develop debilitating, stress-associated disorders later in life, such as major depressive disorder (MDD). Until now, mouse models of depression have been largely unsuccessful at replicating the diverse symptomatology of this disease and the sex bias in vulnerability. From P4 to P11, a limited bedding model that leads to fragmented maternal care, was used to induce ELS...
September 6, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Lawrence Park, Maura Furey, Allison C Nugent, Cristan Farmer, Jessica Ellis, Joanna Szczepanik, Marc S Lener, Carlos A Zarate
Background: This randomized, placebo-controlled, crossover trial examined the antidepressant efficacy of the muscarinic antagonist scopolamine in major depressive disorder subjects with more severe and refractory forms of major depressive disorder relative to previous reports. Methods: Participants included 23 medication-free major depressive disorder subjects (12 F/11 M, 20-55 years) currently experiencing a major depressive episode. Subjects had scored ≥20 on the Montgomery-Asberg Depression Rating Scale...
September 1, 2018: International Journal of Neuropsychopharmacology
Rejish K Thomas, Glen Baker, John Lind, Serdar Dursun
BACKGROUND: Intravenous ketamine has been established as an efficacious and safe treatment, with transient effect, for treatment-resistant depression. However, the effectiveness of intravenous ketamine in non-research settings and with ultraresistant depression patients remains understudied. AIMS: This study aims to measure the response and remission rates in ultraresistant depression patients in a clinical setting by means of a retrospective, open label, database study...
September 5, 2018: Journal of Psychopharmacology
Yang Zhou, Yuming Peng, Jinghan Fang, Wanchen Sun, Guofu Zhang, Long Zhen, Gang Wang, Ruquan Han
BACKGROUND: Perioperative depressive symptoms (PDS) are common mental comorbidities that influence clinical outcomes and prognosis. However, there is no rapid-acting treatment to address these symptoms during a limited hospital stay. METHODS/DESIGN: This is a single-center, randomized, placebo-controlled, and double-blind trial. Randomization will be applied and stratified by the severity of PDS (moderate versus severe). Eighty patients who are scheduled for elective supratentorial brain tumor resection with PDS will be randomly allocated to the ketamine or placebo group with a ratio of 1 to 1...
August 29, 2018: Trials
Nolan R Williams, Boris D Heifets, Christine Blasey, Keith Sudheimer, Jaspreet Pannu, Heather Pankow, Jessica Hawkins, Justin Birnbaum, David M Lyons, Carolyn I Rodriguez, Alan F Schatzberg
OBJECTIVE: In addition to N-methyl-d-aspartate receptor antagonism, ketamine produces opioid system activation. The objective of this study was to determine whether opioid receptor antagonism prior to administration of intravenous ketamine attenuates its acute antidepressant or dissociative effects. METHOD: In a proposed double-blind crossover study of 30 adults with treatment-resistant depression, the authors performed a planned interim analysis after studying 14 participants, 12 of whom completed both conditions in randomized order: placebo or 50 mg of naltrexone preceding intravenous infusion of 0...
August 29, 2018: American Journal of Psychiatry
Mu-Hong Chen, Cheng-Ta Li, Wei-Chen Lin, Chen-Jee Hong, Pei-Chi Tu, Ya-Mei Bai, Chih-Ming Cheng, Tung-Ping Su
Increasing evidence supports the rapid antidepressant effect of a low-dose ketamine infusion in treatment-resistant depression (TRD). Proinflammatory cytokines play a crucial role in the pathophysiology of TRD. However, it is unknown whether the rapid antidepressant effect of ketamine is related to the rapid suppression of proinflammatory cytokines. Seventy-one patients with TRD were randomized into three groups according to the treatment received: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, and normal saline infusion...
August 21, 2018: Psychiatry Research
Tony Ye, Mitchell J Bartlett, Matthew B Schmit, Scott J Sherman, Torsten Falk, Stephen L Cowen
Introduction: Treatment-resistant depression, post-traumatic stress disorder, chronic pain, and L-DOPA-induced dyskinesia in Parkinson's disease are characterized by hypersynchronous neural oscillations. Sub-anesthetic ketamine is effective at treating these conditions, and this may relate to ketamine's capacity to reorganize oscillatory activity throughout the brain. For example, a single ketamine injection increases gamma (∼40 Hz) and high-frequency oscillations (HFOs, 120-160 Hz) in the cortex, hippocampus, and striatum...
2018: Frontiers in Neural Circuits
Garret Weber, JuHan Yao, Shemeica Binns, Shinae Namkoong
Chronic neuropathic pain and depression are often comorbid. Ketamine has been used to treat refractory pain. There is emerging evidence for use in depression. We present a case of a pediatric patient who was successfully treated with subanesthetic intravenous ketamine infusion for chronic neuropathic pain and suicidality.
2018: Case Reports in Anesthesiology
Wenyan Cui, Yuping Ning, Wu Hong, Ju Wang, Zhening Liu, Ming D Li
Depression is a worldwide illness with a significant impact on both family and society. Conventional antidepressants are ineffective for more than 30% of patients. In such patients, who have what is called treatment-resistant depression (TRD), inflammatory biomarkers are expressed excessively in both the central nervous system (CNS) and the peripheral blood. Ketamine, a glutamate receptor antagonist, exerts a rapid and sustained therapeutic effect in patients with TRD. Thus, the investigation of the relations between inflammation and glutamate underlying depression has drawn great attention...
August 23, 2018: Molecular Neurobiology
Jennifer L Jones, Camilo F Mateus, Robert J Malcolm, Kathleen T Brady, Sudie E Back
Background: Despite advances in behavioral and pharmacotherapy interventions, substance use disorders (SUDs) are frequently refractory to treatment. Glutamatergic dysregulation has received increasing attention as one common neuropathology across multiple substances of abuse. Ketamine is a potent N-methyl-D-aspartate (NMDA) glutamatergic receptor antagonist which has been found to be effective in the treatment of severe depression. Here we review the literature on the efficacy of ketamine in the treatment of SUDs...
2018: Frontiers in Psychiatry
Mark Jeremy Hunt, Natalie E Adams, Władysław Średniawa, Daniel K Wójcik, Anna Simon, Stefan Kasicki, Miles Adrian Whittington
High-frequency neuronal population oscillations (HFO, 130-180 Hz) are robustly potentiated by subanesthetic doses of ketamine. This frequency band has been recorded in functionally and neuroanatomically diverse cortical and subcortical regions, notably ventral striatal areas. However, the locus of generation remains largely unknown. There is compelling evidence that olfactory regions can drive oscillations in distant areas. Here we tested the hypothesis that the olfactory bulb (OB) is a locus for the generation of HFO following a subanesthetic dose of ketamine...
August 8, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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