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Ketamine, major depressive disorder, treatment resistant

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https://www.readbyqxmd.com/read/27830574/inflammation-effects-on-brain-glutamate-in-depression-mechanistic-considerations-and-treatment-implications
#1
Ebrahim Haroon, Andrew H Miller
There has been increasing interest in the role of glutamate in mood disorders, especially given the profound effect of the glutamate receptor antagonist ketamine in improving depressive symptoms in patients with treatment-resistant depression. One pathway by which glutamate alterations may occur in mood disorders involves inflammation. Increased inflammation has been observed in a significant subgroup of patients with mood disorders, and inflammatory cytokines have been shown to influence glutamate metabolism through effects on astrocytes and microglia...
November 10, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27738380/treatment-resistant-depression-with-loss-of-antidepressant-response-rapid-acting-antidepressant-action-of-dextromethorphan-a-possible-treatment-bridging-molecule
#2
Edward C Lauterbach
Dextromethorphan (DM) may have ketamine-like rapid-acting, treatment-resistant, and conventional antidepressant effects.(1,2) This reports our initial experience with DM in unipolar Major Depressive Disorder (MDD). A patient with treatment-resistant MDD (failing adequate trials of citalopram and vortioxetine) with loss of antidepressant response (to fluoxetine and bupropion) twice experienced a rapid-acting antidepressant effect within 48 hours of DM administration and lasting 7 days, sustained up to 20 days with daily administration, then gradually developing labile loss of antidepressant response over the ensuing 7 days...
August 15, 2016: Psychopharmacology Bulletin
https://www.readbyqxmd.com/read/27718369/change-in-cytokine-levels-is-not-associated-with-rapid-antidepressant-response-to-ketamine-in-treatment-resistant-depression
#3
Minkyung Park, Laura E Newman, Philip W Gold, David A Luckenbaugh, Peixiong Yuan, Rodrigo Machado-Vieira, Carlos A Zarate
Several pro-inflammatory cytokines have been implicated in depression and in antidepressant response. This exploratory analysis assessed: 1) the extent to which baseline cytokine levels predicted positive antidepressant response to ketamine; 2) whether ketamine responders experienced acute changes in cytokine levels not observed in non-responders; and 3) whether ketamine lowered levels of pro-inflammatory cytokines, analogous to the impact of other antidepressants. Data from double-blind, placebo-controlled studies of patients with major depressive disorder (MDD) or bipolar disorder (BD) who received a single infusion of sub-anesthetic dose ketamine were used (N = 80)...
January 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/27692010/exploring-a-post-traumatic-stress-disorder-paradigm-in-flinders-sensitive-line-rats-to-model-treatment-resistant-depression-ii-response-to-antidepressant-augmentation-strategies
#4
Sarel Jacobus Brand, Brian Herbert Harvey
OBJECTIVE: Post-traumatic stress disorder (PTSD) displays high co-morbidity with major depression and treatment-resistant depression (TRD). Earlier work demonstrated exaggerated depressive-like symptoms in a gene×environment model of TRD and an abrogated response to imipramine. We extended the investigation by studying the behavioural and monoaminergic response to multiple antidepressants, viz. venlafaxine and ketamine with/without imipramine. METHODS: Male Flinders sensitive line (FSL) rats, a genetic model of depression, were exposed to a time-dependent sensitisation (TDS) model of PTSD and compared with stress naive controls...
October 3, 2016: Acta Neuropsychiatrica
https://www.readbyqxmd.com/read/27660449/the-interactive-effects-of-ketamine-and-magnesium-upon-depressive-like-pathology
#5
Sara Razmjou, Darcy Litteljohn, Chris Rudyk, Shuaib Syed, Melanie Clarke, Rowan Pentz, Zach Dwyer, Shawn Hayley
Approximately one-third of patients with major depressive disorders (MDDs) are resistant to current treatment methods, and the majority of cases relapse at some point during therapy. This has resulted in novel treatments being adopted, including subanesthetic doses of ketamine, which affects aberrant neuroplastic circuits, glutamatergic signaling, and the production of brain-derived neurotrophic factor. Ketamine rapidly relieves depressive symptoms in treatment-resistant major depressive disorder patients with effects that last for up to 2 weeks even after a single administration...
2016: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/27648916/metabolomic-signatures-of-drug-response-phenotypes-for-ketamine-and-esketamine-in-subjects-with-refractory-major-depressive-disorder-new-mechanistic-insights-for-rapid-acting-antidepressants
#6
D M Rotroff, D G Corum, A Motsinger-Reif, O Fiehn, N Bottrel, W C Drevets, J Singh, G Salvadore, R Kaddurah-Daouk
Ketamine, at sub-anesthetic doses, is reported to rapidly decrease depression symptoms in patients with treatment-resistant major depressive disorder (MDD). Many patients do not respond to currently available antidepressants, (for example, serotonin reuptake inhibitors), making ketamine and its enantiomer, esketamine, potentially attractive options for treatment-resistant MDD. Although mechanisms by which ketamine/esketamine may produce antidepressant effects have been hypothesized on the basis of preclinical data, the neurobiological correlates of the rapid therapeutic response observed in patients receiving treatment have not been established...
September 20, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27623117/-clinical-and-biological-predictors-of-ketamine-response-in-treatment-resistant-major-depression-review
#7
B Romeo, W Choucha, P Fossati, J-Y Rotge
OBJECTIVE: The aim of this review was to determine the clinical and biological predictors of the ketamine response. METHODS: A systematic research on PubMed and PsycINFO database was performed without limits on year of publication. RESULTS: The main predictive factors of ketamine response, which were found in different studies, were (i) a family history of alcohol dependence, (ii) unipolar depressive disorder, and (iii) neurocognitive impairments, especially a slower processing speed...
September 9, 2016: L'Encéphale
https://www.readbyqxmd.com/read/27510426/genetic-studies-on-the-tripartite-glutamate-synapse-in-the-pathophysiology-and-therapeutics-of-mood-disorders
#8
Rafael T de Sousa, Alexandre A Loch, André F Carvalho, André R Brunoni, Marie Reine Haddad, Ioline D Henter, Carlos A Zarate, Rodrigo Machado-Vieira
Both bipolar disorder (BD) and major depressive disorder (MDD) have high morbidity and share a genetic background. Treatment options for these mood disorders are currently suboptimal for many patients; however, specific genetic variables may be involved in both pathophysiology and response to treatment. Agents such as the glutamatergic modulator ketamine are effective in treatment-resistant mood disorders, underscoring the potential importance of the glutamatergic system as a target for improved therapeutics...
September 28, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27489070/new-use-for-an-old-drug-oral-ketamine-for-treatment-resistant-depression
#9
Kevin M Swiatek, Kim Jordan, Julie Coffman
Treatment-resistant depression (TRD) is a disabling disorder that can interfere with a patient's capacity to understand and participate in medical care and thus negatively impact individual morbidity and mortality. Hospitalised patients with TRD may require rapid alleviation of severe symptomatology, particularly when suicidal or if unable to participate in care decisions. Ketamine is well known for its anaesthetic effects and its use as a 'street' drug; however, its action as an N-methyl-D-aspartate receptor antagonist makes ketamine a potential therapy for TRD...
2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27354907/ketamine-enantiomers-in-the-rapid-and-sustained-antidepressant-effects
#10
REVIEW
John Muller, Sahana Pentyala, James Dilger, Srinivas Pentyala
Recent evidence has suggested that the N-methyl-D-aspartate receptor antagonist ketamine shows significant therapeutic effects in major depression and bipolar disorder. This effect is especially important in treatment-resistant depression and depression with suicidal ideation. In this review we explain the mechanism of action, drug efficacy, and the side effects of ketamine; the antidepressive effects of ketamine; the individual effects of ketamine isomers, R(-) ketamine and S(+) ketamine; the effects of the combination of ketamine with electroconvulsive therapy; and the possible use of ketamine in treating depression...
June 2016: Therapeutic Advances in Psychopharmacology
https://www.readbyqxmd.com/read/27232360/rapid-and-sustained-reductions-in-current-suicidal-ideation-following-repeated-doses-of-intravenous-ketamine-secondary-analysis-of-an-open-label-study
#11
Dawn F Ionescu, Michaela B Swee, Kara J Pavone, Norman Taylor, Oluwaseun Akeju, Lee Baer, Maren Nyer, Paolo Cassano, David Mischoulon, Jonathan E Alpert, Emery N Brown, Matthew K Nock, Maurizio Fava, Cristina Cusin
BACKGROUND: Ketamine rapidly reduces thoughts of suicide in patients with treatment-resistant depression who are at low risk for suicide. However, the extent to which ketamine reduces thoughts of suicide in depressed patients with current suicidal ideation remains unknown. METHODS: Between April 2012 and October 2013, 14 outpatients with DSM-IV-diagnosed major depressive disorder were recruited for the presence of current, stable (≥ 3 months) suicidal thoughts...
June 2016: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/27062450/ketamine-for-treatment-resistant-unipolar-and-bipolar-major-depression-critical-review-and-implications-for-clinical-practice
#12
REVIEW
William V Bobo, Jennifer L Vande Voort, Paul E Croarkin, Jonathan G Leung, Susannah J Tye, Mark A Frye
There is an urgent need for more rapidly effective pharmacotherapies for major depressive disorder and bipolar disorder (BP) that are efficacious and tolerable for depressed patients who respond poorly to conventional treatments. Multiple controlled trials have now demonstrated a rapid, nonsustained antidepressive response to a single intravenous infusion of ketamine. Early controlled studies of intranasal or serial infusion therapy appear promising. The effective dose for depression is lower than the typical anesthetic doses, and side-effects are generally mild and transient...
August 2016: Depression and Anxiety
https://www.readbyqxmd.com/read/27062302/ketamine-s-mechanism-of-action-a-path-to-rapid-acting-antidepressants
#13
REVIEW
Chadi G Abdallah, Thomas G Adams, Benjamin Kelmendi, Irina Esterlis, Gerard Sanacora, John H Krystal
Major depressive disorder (MDD) is a common and debilitating psychiatric disorder. Traditional antidepressants are of limited efficacy and take weeks to months to yield full therapeutic effects. Thus, there is a clear need for effective rapid-acting antidepressant medications. The N-methyl-d-aspartate receptor (NMDA-R) antagonist, ketamine, has received a great deal of attention over the last 20 years due to the discovery that a single subanesthetic dose leads to a rapid antidepressant effect in individuals with treatment-resistant depression...
August 2016: Depression and Anxiety
https://www.readbyqxmd.com/read/27053196/ketamine-for-treatment-resistant-depression-recent-developments-and-clinical-applications
#14
Jaclyn Schwartz, James W Murrough, Dan V Iosifescu
Approximately one-third of patients with major depressive disorder (MDD) do not respond to existing antidepressants, and those who do generally take weeks to months to achieve a significant effect. There is a clear unmet need for rapidly acting and more efficacious treatments. We will review recent developments in the study of ketamine, an old anaesthetic agent which has shown significant promise as a rapidly acting antidepressant in treatment-resistant patients with unipolar MDD, focusing on clinically important aspects such as dose, route of administration and duration of effect...
May 2016: Evidence-based Mental Health
https://www.readbyqxmd.com/read/27046644/the-role-of-adipokines-in-the-rapid-antidepressant-effects-of-ketamine
#15
R Machado-Vieira, P W Gold, D A Luckenbaugh, E D Ballard, E M Richards, I D Henter, R T De Sousa, M J Niciu, P Yuan, C A Zarate
We previously found that body mass index (BMI) strongly predicted response to ketamine. Adipokines have a key role in metabolism (including BMI). They directly regulate inflammation and neuroplasticity pathways and also influence insulin sensitivity, bone metabolism and sympathetic outflow; all of these have been implicated in mood disorders. Here, we sought to examine the role of three key adipokines-adiponectin, resistin and leptin-as potential predictors of response to ketamine or as possible transducers of its therapeutic effects...
April 5, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/26995153/the-role-of-gsk-3-in-treatment-resistant-depression-and-links-with-the-pharmacological-effects-of-lithium-and-ketamine-a-review-of-the-literature
#16
J F Costemale-Lacoste, J P Guilloux, R Gaillard
BACKGROUND: Since the discovery of antidepressants, new treatments have emerged with fewer side effects but no greater efficacy. Glycogen synthase kinase 3 β (GSK-3β), a kinase known for its activity on glycogen synthesis, has in the last few years raised growing interest in biological psychiatry. Several efficient treatments in major depression have an inhibitory effect on this kinase, which could be targeted in new mood disorder treatments. METHODS: The aim of this review is to summarize findings concerning the intracellular pharmacologic effects of GSK-3β inhibitors on mood...
April 2016: L'Encéphale
https://www.readbyqxmd.com/read/26830963/multiple-non-equivalent-interfaces-mediate-direct-activation-of-gabaa-receptors-by-propofol
#17
REVIEW
Megan M Eaton, Allison L Germann, Ruby Arora, Lily Q Cao, Xiaoyi Gao, Daniel J Shin, Albert Wu, David C Chiara, Jonathan B Cohen, Joe Henry Steinbach, Alex S Evers, Gustav Akk
BACKGROUND: Propofol is a sedative agent that at clinical concentrations acts by allosterically activating or potentiating the γ-aminobutyric acid type A (GABAA) receptor. Mutational, modeling, and photolabeling studies with propofol and its analogues have identified potential interaction sites in the transmembrane domain of the receptor. At the "+" of the β subunit, in the β-α interface, meta-azipropofol labels the M286 residue in the third transmembrane domain...
2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/26783510/current-status-of-ketamine-and-related-therapies-for-mood-and-anxiety-disorders
#18
Sara Costi, Nicholas T Van Dam, James W Murrough
Major Depressive Disorder (MDD) is a leading cause of disability worldwide. Despite a plethora of established treatments, less than one-third of individuals with MDD achieve stable remission of symptoms. Given limited efficacy and significant lag time to onset of therapeutic action among conventional antidepressants, interest has shifted to treatments that act outside of the monoamine neurotransmitter systems (e.g., serotonin, norepinephrine, and dopamine). Preclinical and clinical research on the glutamate system has been particularly promising in this regard...
December 2015: Current Behavioral Neuroscience Reports
https://www.readbyqxmd.com/read/26768892/is-off-label-repeat-prescription-of-ketamine-as-a-rapid-antidepressant-safe-controversies-ethical-concerns-and-legal-implications
#19
Melvyn W Zhang, Keith M Harris, Roger C Ho
BACKGROUND: Depressive disorders are a common form of psychiatric illness and cause significant disability. Regulation authorities, the medical profession and the public require high safety standards for antidepressants to protect vulnerable psychiatric patients. Ketamine is a dissociative anaesthetic and a derivative of a hallucinogen (phencyclidine). Its abuse is a major worldwide public health problem. Ketamine is a scheduled drug and its usage is restricted due to its abuse liability...
2016: BMC Medical Ethics
https://www.readbyqxmd.com/read/26644333/long-term-effect-of-sub-anesthetic-ketamine-in-reducing-l-dopa-induced-dyskinesias-in-a-preclinical-model
#20
Mitchell J Bartlett, Ria M Joseph, Lindsey M LePoidevin, Kate L Parent, Nicholas D Laude, Levi B Lazarus, Michael L Heien, Miguel Estevez, Scott J Sherman, Torsten Falk
Low-dose sub-anesthetic ketamine infusion treatment has led to a long-term reduction of treatment-resistant depression and posttraumatic stress disorder (PTSD) symptom severity, as well as reduction of chronic pain states, including migraine headaches. Ketamine also is known to change oscillatory electric brain activity. One commonality between migraine headaches, depression, PTSD, Parkinson's disease (PD) and l-DOPA-induced dyskinesias (LID) is hypersynchrony of electric activity in the brain, including the basal ganglia...
January 26, 2016: Neuroscience Letters
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