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Ketamine and treatment resistant depression

Verònica Gálvez, Adrienne Li, Christina Huggins, Paul Glue, Donel Martin, Andrew A Somogyi, Angelo Alonzo, Anthony Rodgers, Philip B Mitchell, Colleen K Loo
BACKGROUND: Ketamine research in depression has mostly used intravenous, weight-based approaches, which are difficult to translate clinically. Intranasal (IN) ketamine is a promising alternative but no controlled data has been published on the feasibility, safety and potential efficacy of repeated IN ketamine treatments. METHODS: This randomised, double-blind, placebo-controlled pilot study compared a 4-week course of eight treatments of 100 mg ketamine or 4.5 mg midazolam...
March 1, 2018: Journal of Psychopharmacology
Mark J Niciu, Bridget J Shovestul, Brittany A Jaso, Cristan Farmer, David A Luckenbaugh, Nancy E Brutsche, Lawrence T Park, Elizabeth D Ballard, Carlos A Zarate
BACKGROUND: Ketamine induces rapid and robust antidepressant effects, and many patients also describe dissociation, which is associated with antidepressant response. This follow-up study investigated whether antidepressant efficacy is uniquely related to dissociative symptom clusters. METHODS: Treatment-resistant patients with major depressive disorder (MDD) or bipolar disorder (BD) (n = 126) drawn from three studies received a single subanesthetic (0.5 mg/kg) ketamine infusion...
February 17, 2018: Journal of Affective Disorders
A P Allen, M Naughton, J Dowling, A Walsh, R O'Shea, G Shorten, L Scott, D M McLoughlin, J F Cryan, G Clarke, T G Dinan
Current first-line antidepressants can take weeks or months to decrease depressive symptoms. Low dose ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, shows potential for a more rapid antidepressant effect, with efficacy also evident in previously treatment-resistant populations. However, a greater understanding of the physiological mechanisms underlying such effects is required. We assessed the potential impact of ketamine infusion on neurobiological drivers of kynurenine pathway metabolism in major depression (HPA axis hyperactivity, inflammation) in patients with treatment-resistant depression compared to gender-matched healthy controls...
February 10, 2018: Journal of Psychiatric Research
Dawn F Ionescu, Julia M Felicione, Aishwarya Gosai, Cristina Cusin, Philip Shin, Benjamin G Shapero, Thilo Deckersbach
Major depressive disorder (MDD) is one of the most prevalent conditions in psychiatry. Patients who do not respond to traditional monoaminergic antidepressant treatments have an especially difficult-to-treat type of MDD termed treatment-resistant depression. Subanesthetic doses of ketamine-a glutamatergic modulator-have shown great promise for rapidly treating patients with the most severe forms of depression. As such, ketamine represents a promising probe for understanding the pathophysiology of depression and treatment response...
February 20, 2018: Harvard Review of Psychiatry
Elizabeth D Ballard, Julia S Yarrington, Cristan A Farmer, Marc S Lener, Bashkim Kadriu, Níall Lally, Deonte Williams, Rodrigo Machado-Vieira, Mark J Niciu, Lawrence Park, Carlos A Zarate
BACKGROUND: Due to the heterogeneity of depressive symptoms-which can include depressed mood, anhedonia, negative cognitive biases, and altered activity levels-researchers often use a combination of depression rating scales to assess symptoms. This study sought to identify unidimensional constructs measured across rating scales for depression and to evaluate these constructs across clinical trials of a rapid-acting antidepressant (ketamine). METHODS: Exploratory factor analysis (EFA) was conducted on baseline ratings from the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Snaith-Hamilton Pleasure Rating Scale (SHAPS)...
February 5, 2018: Journal of Affective Disorders
Chinnakkaruppan Adaikkan, Elham Taha, Iliana Barrera, Orit David, Kobi Rosenblum
BACKGROUND: Ketamine is an N-methyl-D-aspartate receptor antagonist, which on administration produces fast-acting antidepressant responses in patients with major depressive disorder. Yet, the mechanism underlying the antidepressant action of ketamine remains unclear. METHODS: To unravel the mechanism of action of ketamine, we treated wild-type C57BL/6 mice with calcium/calmodulin-dependent protein kinase II (CaMKII) specific inhibitor tatCN21 peptide. We also used eukaryotic elongation factor 2 kinase (eEF2K) (also known as CaMKIII) knockout mice...
December 5, 2017: Biological Psychiatry
Haiying Tang, Daniel Kukral, Yu-Wen Li, Matthew Fronheiser, Harold Malone, Adrienne Pena, Rick Pieschl, Kurex Sidik, Gabriel Tobon, Patrick L Chow, Linda J Bristow, Wendy Hayes, Feng Luo
Major depressive disorder is a leading cause of disability globally. Improvements in the efficacy of antidepressant therapy are needed as a high proportion (>40%) of individuals with major depressive disorder fail to respond adequately to current treatments. The non-selective N-methyl-D-aspartate receptor channel blocker, (±)-ketamine, has been reported to produce a rapid and long-lasting antidepressant response in treatment-resistant major depressive disorder patients, which provides a unique opportunity for investigation of mechanisms that mediate its therapeutic effect...
January 1, 2018: Journal of Psychopharmacology
J H Kwon, W S Sim, J P Hong, I S Song, J Y Lee
WHAT IS KNOWN AND OBJECTIVE: Ketamine in a subanaesthetic dose has been shown to produce rapid antidepressant effects. Here, we describe a long-term follow-up case of a Korean patient with severe major depression who received repeated ketamine intravenous therapy (KIT). CASE DESCRIPTION: A 49-year-old woman with a 6-year history of treatment-resistant major depression was given KIT once every 1 or 2 weeks over 10 months, for a total of 36 treatments. Her mood stabilized, and she showed a nearly 50% reduction in the severity of her depressive symptom...
January 25, 2018: Journal of Clinical Pharmacy and Therapeutics
Ira Byock
BACKGROUND: Psychiatric research in the 1950s and 1960s showed potential for psychedelic medications to markedly alleviate depression and suffering associated with terminal illness. More recent published studies have demonstrated the safety and efficacy of psilocybin, MDMA, and ketamine when administered in a medically supervised and monitored approach. A single or brief series of sessions often results in substantial and sustained improvement among people with treatment-resistant depression and anxiety, including those with serious medical conditions...
January 22, 2018: Journal of Palliative Medicine
Michael E Thase
There is a great unmet need for new medications with novel mechanisms of action that can effectively treat patients who do not benefit from standard antidepressant therapies. After a period in which it seemed as if the pharmaceutical pipeline for new antidepressants was going dry, the past decade has witnessed renewed interest, beginning with discovery of the antidepressant effects of ketamine. This article briefly highlights more recent research on ketamine and other investigational antidepressants.
December 2017: CNS Spectrums
Tero Taiminen
Ketamine infusions administered intravenously 1 to 3 times per week are the quickest and most effective treatment for depression. Short-course ketamine medication is established treatment both for unipolar depression and depressive episodes of bipolar affective disorder. Ketamine is suitable for initiating the treatment for treatment-resistant depression, alleviation of suicidal tendencies, and treatment of depressive patients suffering from simultaneous pain. The safety of prolonged treatment with ketamine is not known to sufficient degree...
2017: Duodecim; Lääketieteellinen Aikakauskirja
N Yao, O Skiteva, X Zhang, P Svenningsson, K Chergui
Low doses of ketamine trigger rapid and lasting antidepressant effects after one injection in treatment-resistant patients with major depressive disorder. Modulation of AMPA receptors (AMPARs) in the hippocampus and prefrontal cortex is suggested to mediate the antidepressant action of ketamine and of one of its metabolites (2R,6R)-hydroxynorketamine ((2R,6R)-HNK). We have examined whether ketamine and (2R,6R)-HNK affect glutamatergic transmission and plasticity in the mesolimbic system, brain regions known to have key roles in reward-motivated behaviors, mood and hedonic drive...
November 21, 2017: Molecular Psychiatry
John Hartberg, Simone Garrett-Walcott, Angelo De Gioannis
RATIONALE: Depressive episodes are the leading cause of mental health-related hospital admissions in Australia, and 44% of those admitted have a previous history of hospitalisations for depression (Admitted patient mental health-related care: (Australian Institute of Health and Welfare Aust Hospital Stat 2011-12, 2013). Despite numerous available antidepressant treatments, many patients do not respond to conventional therapy, having what is called 'treatment resistance' (Fava Biol Psychiatry 53:649-659, 2003)...
November 18, 2017: Psychopharmacology
Katja Weckmann, Michael J Deery, Julie A Howard, Renata Feret, John M Asara, Frederik Dethloff, Michaela D Filiou, Jamie Iannace, Christiana Labermaier, Giuseppina Maccarrone, Christian Webhofer, Larysa Teplytska, Kathryn Lilley, Marianne B Müller, Christoph W Turck
Fewer than 50% of all patients with major depressive disorder (MDD) treated with currently available antidepressants (ADs) show full remission. Moreover, about one third of the patients suffering from MDD does not respond to conventional ADs and develop treatment-resistant depression (TRD). Ketamine, a non-competitive, voltage-dependent N-Methyl-D-aspartate receptor (NMDAR) antagonist, has been shown to have a rapid antidepressant effect, especially in patients suffering from TRD. Hippocampi of ketamine-treated mice were analysed by metabolome and proteome profiling to delineate ketamine treatment-affected molecular pathways and biosignatures...
November 17, 2017: Scientific Reports
Youge Qu, Chun Yang, Qian Ren, Min Ma, Chao Dong, Kenji Hashimoto
Accumulating evidence suggests a key role of the gut-microbiota-brain axis in the antidepressant actions of certain compounds. Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, showed rapid and sustained antidepressant effects in treatment-resistant depressed patients. In contrast, another NMDAR antagonist, lanicemine, did not exhibit antidepressant effects in such patients. (R)-ketamine, the (R)-enantiomer of ketamine, has rapid-acting and long-lasting antidepressant effects in rodent models of depression...
November 16, 2017: Scientific Reports
Carolina Medeiros da Frota Ribeiro, Patricio Riva-Posse
PURPOSE OF REVIEW: The purpose of this paper is to provide a review of the use of ketamine as an antidepressant for treatment-resistant depression (TRD) in the geriatric population. Available treatment options for late-life treatment-resistant depression are limited and include electroconvulsive therapy and transcranial magnetic stimulation as well as possible pharmacologic augmentation. Ketamine has been shown to be a promising treatment in TRD; however, data regarding the use of ketamine in the elderly includes only five case reports...
November 15, 2017: Current Psychiatry Reports
Jennifer Abbasi
No abstract text is available yet for this article.
November 28, 2017: JAMA: the Journal of the American Medical Association
Eric A Maltbie, Gopinath S Kaundinya, Leonard L Howell
Ketamine has been used as a pharmacological model for schizophrenia as subanesthetic infusions have been shown to produce temporary schizophrenia-like symptoms in healthy humans. More recently, ketamine has emerged as a potential treatment for multiple psychiatric disorders, including treatment-resistant depression and suicidal ideation. However, the mechanisms underlying both the psychotomimetic and the therapeutic effects of ketamine remain poorly understood. This review provides an overview of what is known of the neural mechanisms underlying the effects of ketamine and details what functional MRI studies have yielded at a systems level focused on brain circuitry...
December 2017: Behavioural Pharmacology
Kenji Hashimoto
Depression is often misdiagnosed as major depressive disorder in patients with bipolar disorder. Therapeutic drugs for these two disorders are quite different, but the anesthetic ketamine shows fast-acting antidepressant effects in treatment-resistant patients with these disorders. Here, we discuss biomarkers for both disorders, recent findings regarding ketamine, and predictable biomarkers for ketamine's antidepressant actions.
October 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
Mark J Niciu, Nicolas D Iadarola, Dipavo Banerjee, David A Luckenbaugh, Minkyung Park, Marc Lener, Lawrence Park, Dawn F Ionescu, Elizabeth D Ballard, Nancy E Brutsche, Nirmala Akula, Francis J McMahon, Rodrigo Machado-Vieira, Allison C Nugent, Carlos A Zarate
BACKGROUND: This study sought to reproduce, in a larger sample, previous findings of a correlation between smaller raw 3-Tesla (3T) hippocampal volumes and improved antidepressant efficacy of ketamine in individuals with major depressive disorder (MDD). A secondary analysis stratified subjects according to functional BDNF rs6265 (val66met) genotype. METHODS: Unmedicated subjects with treatment-resistant MDD ( n=55) underwent baseline structural 3T MRI. Data processing was conducted with FSL/FIRST and Freesurfer software...
December 2017: Journal of Psychopharmacology
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