Read by QxMD icon Read

Ketamine and treatment resistant depression

Mariusz Papp, Piotr Gruca, Magdalena Lason-Tyburkiewicz, Paul Willner
Ketamine is the prototype of a new generation of antidepressant drugs, which is reported in clinical studies to be effective in treatment-resistant patients, with an effect that appears within hours and lasts for a few days. Chronic mild stress (CMS) is a well-established and widely used animal model of depression, in which anhedonia, anxiogenesis and cognitive dysfunction can be observed reliably. Studies using acute or brief ketamine treatment following withdrawal from CMS have replicated the clinical finding of a rapid onset of antidepressant action...
October 18, 2016: Behavioural Pharmacology
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
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)...
September 30, 2016: Journal of Psychiatric Research
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
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
Jennifer L Vande Voort, Robert J Morgan, Simon Kung, Keith G Rasmussen, Jose Rico, Brian A Palmer, Kathryn M Schak, Susannah J Tye, Matthew J Ritter, Mark A Frye, William V Bobo
BACKGROUND: Little is known about the antidepressive effects of repeated intravenous ketamine infusions beyond the acute phase of treatment in patients with refractory depression. METHODS: Twelve subjects with treatment-resistant non-psychotic unipolar or bipolar major depression and suicidal ideation were given repeated (up to 6) thrice-weekly acute-phase intravenous infusions of ketamine (0.5mg/kg, administered over 100min). Those who remitted during acute-phase treatment received continuation-phase treatment that consisted of 4 weekly ketamine infusions, followed by 4 weeks of post-continuation phase follow-up (during which no further ketamine infusions were administered)...
September 12, 2016: Journal of Affective Disorders
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...
2016: Translational Psychiatry
Kenji Hashimoto
The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine is one of the most attractive antidepressants since this drug causes rapid-onset and sustained antidepressant effects in treatment resistant patients with depression. There are unanswered questions about how ketamine induces its rapid and sustained antidepressant actions. This key article suggests that (2R,6R)-HNK (hydroxynorketamine), a major metabolite of (R)-ketamine, shows antidepressant effects in rodent models of depression, indicating that the metabolism of (R)-ketamine to (2R,6R)-HNK is pivotal in its antidepressant action...
November 2016: Expert Opinion on Therapeutic Targets
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
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. Glutamatergic agents such as the N-methyl-D-aspartate (NMDA) antagonist ketamine are effective in treatment-resistant mood disorders, underscoring the potential importance of the glutamatergic system as a target for improved therapeutics...
August 11, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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
A Gururajan, M E Naughton, K A Scott, R M O'Connor, G Moloney, G Clarke, J Dowling, A Walsh, F Ismail, G Shorten, L Scott, D M McLoughlin, J F Cryan, T G Dinan
There is a growing emphasis in the field of psychiatry on the need to identify candidate biomarkers to aid in diagnosis and clinical management of depression, particularly with respect to predicting response to specific therapeutic strategies. MicroRNAs are small nucleotide sequences with the ability to regulate gene expression at the transcriptomic level and emerging evidence from a range of studies has highlighted their biomarker potential. Here we compared healthy controls (n=20) with patients diagnosed with major depression (n=40) and who were treatment-resistant to identify peripheral microRNA biomarkers, which could be used for diagnosis and to predict response to electroconvulsive therapy (ECT) and ketamine (KET) infusions, treatments that have previously shown to be effective in treatment-resistant depression (TRD)...
2016: Translational Psychiatry
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
Connor Thelen, Jonathon Sens, Joseph Mauch, Radhika Pandit, Pothitos M Pitychoutis
One of the most striking discoveries in the treatment of major depression was the finding that infusion of a single sub-anesthetic dose of ketamine induces rapid and sustained antidepressant effects in treatment-resistant depressed patients. However, ketamine's antidepressant-like actions are transient and can only be sustained by repeated drug treatment. Despite the fact that women experience major depression at roughly twice the rate of men, research regarding the neurobiological antidepressant-relevant effects of ketamine has focused almost exclusively on the male sex...
October 1, 2016: Behavioural Brain Research
Scott J Sherman, Miguel Estevez, Ari B Magill, Torsten Falk
Ketamine is an FDA-approved drug with a known safety profile. Low-dose subanesthetic intravenous ketamine infusion treatment has led to long-term reduction of treatment-resistant depression and of chronic pain states. We report on low-dose subanesthetic intravenous ketamine infusion treatment in Parkinson's disease (PD) patients by 5 case studies and show a long-lasting therapeutic benefit to reduce l-DOPA-induced dyskinesia (LID), improve on time, and reduce depression. Based on the literature we hypothesize that low-dose ketamine may act as a 'chemical deep brain stimulation', by desynchronizing hypersynchronous oscillatory brain activity, including in the basal ganglia and the motor cortex...
January 2016: Case Reports in Neurology
Kristian Gaarn du Jardin, Heidi Kaastrup Müller, Betina Elfving, Elena Dale, Gregers Wegener, Connie Sanchez
A single i.v. infusion of ketamine, classified as an N-methyl-d-aspartate (NMDA) receptor antagonist, may alleviate depressive symptoms within hours of administration in treatment resistant depressed patients, and the antidepressant effect may last for several weeks. These unique therapeutic properties have prompted researchers to explore the mechanisms mediating the antidepressant effects of ketamine, but despite many efforts, no consensus on its antidepressant mechanism of action has been reached. Recent preclinical reports have associated the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) with the antidepressant-like action of ketamine...
November 3, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
Kristian Gaarn du Jardin, Heidi Kaastrup Müller, Connie Sanchez, Gregers Wegener, Betina Elfving
Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that has been shown to induce a rapid antidepressant effect in treatment-resistant patients. Vortioxetine is a multimodal-acting antidepressant that exert its therapeutic activity through serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibition and modulation of several 5-HT receptors. In clinical trials, vortioxetine improves depression symptoms and cognitive dysfunction. Neuroplasticity as well as serotonergic and glutamatergic signaling attain significant roles in depression pathophysiology and antidepressant responses...
September 5, 2016: European Journal of Pharmacology
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
T H Pham, I Mendez-David, C Defaix, B P Guiard, L Tritschler, D J David, A M Gardier
Unlike classic serotonergic antidepressant drugs, ketamine, an NMDA receptor antagonist, exhibits a rapid and persistent antidepressant (AD) activity, at sub-anaesthetic doses in treatment-resistant depressed patients and in preclinical studies in rodents. The mechanisms mediating this activity are unclear. Here, we assessed the role of the brain serotonergic system in the AD-like activity of an acute sub-anaesthetic ketamine dose. We compared ketamine and fluoxetine responses in several behavioural tests currently used to predict anxiolytic/antidepressant-like potential in rodents...
May 17, 2016: Neuropharmacology
Xiaomei Zhong, Hongbo He, Chunping Zhang, Zhijie Wang, Miaoling Jiang, Qirong Li, Minling Zhang, Xiong Huang
BACKGROUND: Treatment-resistant depression (TRD) is a growing clinical challenge. Electroconvulsive therapy (ECT) is an effective tool for TRD treatment. However, there remains a subset of patients who do not respond to this treatment with common anesthetic agent. Ketamine, a noteworthy anesthetic agent, has emerged as an augmentation to enhance the antidepressant efficacy of ECT. Trials of i.v. ketamine in TRD indicated dose-related mood enhancing efficacy. We aimed to explore anesthetic and subanesthetic concentrations of ketamine in ECT for TRD with respect to their impact on mood and neuropsychological effects...
September 1, 2016: Journal of Affective Disorders
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"