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Ketamine and suicidal ideation

John Burger, Marc Capobianco, Robert Lovern, Ben Boche, Elliot Ross, Michael A Darracq, Robert McLay
BACKGROUND: Rates of completed suicide in the military have increased. Options are limited for acute relief of depression and suicidal ideation. Traditional treatments' effects take weeks to months. A novel, rapid, therapeutic target has emerged with the N-methyl-D-aspartate antagonist ketamine. Previous studies suggest that a single dose of intravenous (IV) ketamine rapidly alleviates depression and suicidality. METHODS: In this proof of concept study, an active duty convenience sample population presenting to the emergency department (ED) meeting criteria for inpatient psychiatric admission as a result of depression and suicidal thinking were randomized to receive either a subdissociative dose (0...
October 2016: Military Medicine
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
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
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
Faryal Mallick, Cheryl B McCullumsmith
Ketamine, an NMDA receptor antagonist with efficacy as a rapid anti-depressant, has early evidence for action to reduce suicidal ideation. This review will explore several important questions that arise from these studies. First, how do we measure reductions in suicidal ideation that occur over minutes to hours? Second, are the reductions in suicidal ideation after ketamine treatment solely a result of its rapid anti-depressant effect? Third, is ketamine only effective in reducing suicidal ideation in patients with mood disorders? Fourth, could ketamine's action lead us to a greater understanding of the neurobiology of suicidal processes? Last, do the reductions in depression and suicidal ideation after ketamine treatment translate into decreased risk for suicidal behavior? Our review concludes that ketamine treatment can be seen as a double-edged sword, clinically to help provide treatment for acutely suicidal patients and experimentally to explore the neurobiological nature of suicidal ideation and suicidal behavior...
June 2016: Current Psychiatry Reports
Samuel T Wilkinson, Gerard Sanacora
Ketamine has attracted widespread attention as a potential rapid-acting antidepressant. There is also considerable interest in its use for the rapid treatment of patients deemed at risk for suicide. Here, we review the available evidence (open-label and randomized controlled trials) that examine the effects of ketamine on suicidal ideation (SI). Overall, data suggest that ketamine has a rapid albeit transient effect in reducing SI, though some studies had mixed results at different time points or using different assessments...
August 2016: Depression and Anxiety
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
Laili Soleimani, Alison Welch, James W Murrough
No abstract text is available yet for this article.
December 2015: Current Treatment Options in Psychiatry
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
Manuella P Kaster, Morgana Moretti, Mauricio P Cunha, Ana Lúcia S Rodrigues
Major depressive disorder is a disabling psychiatric condition that causes a significant burden on individuals and society. There is still a lack of a clear understanding of the neuropathological changes associated with this illness and the efficacy of antidepressants is still far from optimal. Research into antidepressant therapies has evolved from serendipitous observation in human trials, but more than 60 years after the first monoaminergic antidepressants emerged they remain the mainstay for treating depression...
January 15, 2016: European Journal of Pharmacology
Ajay K Parsaik, Balwinder Singh, Darrow Khosh-Chashm, Soniya S Mascarenhas
OBJECTIVE: To consolidate the evidence from the literature to evaluate the role of ketamine in the treatment of bipolar depression. METHODS: Major databases, including MEDLINE, EMBASE, Cochrane, and Scopus, were searched through October 2014, for studies reporting the role of ketamine in the treatment of bipolar depression. Only randomized controlled trials were included in the meta-analysis. We calculated standardized mean differences (SMDs) with SE for each study included in the meta-analysis...
November 2015: Journal of Psychiatric Practice
Parvin Kashani, Shiva Yousefian, Afshin Amini, Kamran Heidari, Somaie Younesian, Hamid Reza Hatamabadi
INTRODUCTION: Suicidal ideation is an emergent problem in the Emergency Department (ED) that often complicates patient disposition and discharge. It has been shown that ketamine possesses fast acting antidepressant and anti-suicidal effects. This study was conducted to examine the effects of a single intravenous bolus of ketamine on patients with suicidal ideations in ED. METHODS: Forty-nine subjects with suicidal ideations with or without an unsuccessful suicide attempt, received 0...
2014: Emergency (Tehran, Iran)
Y-D Hu, Y-T Xiang, J-X Fang, S Zu, S Sha, H Shi, G S Ungvari, C U Correll, H F K Chiu, Y Xue, T-F Tian, A-S Wu, X Ma, G Wang
BACKGROUND: While oral antidepressants reach efficacy after weeks, single-dose intravenous (i.v.) ketamine has rapid, yet time-limited antidepressant effects. We aimed to determine the efficacy and safety of single-dose i.v. ketamine augmentation of escitalopram in major depressive disorder (MDD). METHOD: Thirty outpatients with severe MDD (17-item Hamilton Rating Scale for Depression total score ⩾ 24) were randomized to 4 weeks double-blind treatment with escitalopram 10 mg/day+single-dose i...
February 2016: Psychological Medicine
Rayan K Al Jurdi, Alan Swann, Sanjay J Mathew
Suicide is a major global public health problem and the leading cause of injury mortality in the USA. Suicide is a complex phenomenon involving several systems and neurobiological pathways, with interacting genetic and environmental mechanisms. The literature on the neurobiology and pharmacotherapy of suicide has been limited. To date, no medications have proven efficacious for treating acute suicidal crises. There is an emerging literature supporting a rapid anti-suicidal effect of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, among depressed patients with suicidal ideation...
October 2015: Current Psychiatry Reports
A B Niculescu, D F Levey, P L Phalen, H Le-Niculescu, H D Dainton, N Jain, E Belanger, A James, S George, H Weber, D L Graham, R Schweitzer, T B Ladd, R Learman, E M Niculescu, N P Vanipenta, F N Khan, J Mullen, G Shankar, S Cook, C Humbert, A Ballew, M Yard, T Gelbart, A Shekhar, N J Schork, S M Kurian, G E Sandusky, D R Salomon
Worldwide, one person dies every 40 seconds by suicide, a potentially preventable tragedy. A limiting step in our ability to intervene is the lack of objective, reliable predictors. We have previously provided proof of principle for the use of blood gene expression biomarkers to predict future hospitalizations due to suicidality, in male bipolar disorder participants. We now generalize the discovery, prioritization, validation, and testing of such markers across major psychiatric disorders (bipolar disorder, major depressive disorder, schizoaffective disorder, and schizophrenia) in male participants, to understand commonalities and differences...
November 2015: Molecular Psychiatry
J W Murrough, L Soleimani, K E DeWilde, K A Collins, K A Lapidus, B M Iacoviello, M Lener, M Kautz, J Kim, J B Stern, R B Price, A M Perez, J W Brallier, G J Rodriguez, W K Goodman, D V Iosifescu, D S Charney
BACKGROUND: Suicide is a devastating public health problem and very few biological treatments have been found to be effective for quickly reducing the intensity of suicidal ideation (SI). We have previously shown that a single dose of ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, is associated with a rapid reduction in depressive symptom severity and SI in patients with treatment-resistant depression. METHOD: We conducted a randomized, controlled trial of ketamine in patients with mood and anxiety spectrum disorders who presented with clinically significant SI (n = 24)...
December 2015: Psychological Medicine
Elizabeth D Ballard, David A Luckenbaugh, Erica M Richards, Tessa L Walls, Nancy E Brutsché, Rezvan Ameli, Mark J Niciu, Jennifer L Vande Voort, Carlos A Zarate
Rapid reduction of suicidal thoughts is critical for treating suicidal patients. Clinical trials evaluating these treatments require appropriate measurement. Key methodological issues include: 1) the use of single or multi-item assessments, and 2) evaluating whether suicidal ideation measures can track rapid change over time. The current study presents data from two randomized, placebo-controlled, crossover clinical trials evaluating ketamine in individuals with treatment-resistant depression (n = 60). Participants were assessed for suicidal thoughts using the Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), and Scale for Suicidal Ideation (SSI) at eight time points over three days...
September 2015: Journal of Psychiatric Research
R Rajkumar, J Fam, E Y M Yeo, G S Dawe
Depression and suicide are known to be intricately entwined but the neurobiological basis underlying this association is yet to be understood. Ketamine is an N-methyl d-aspartate (NMDA) receptor antagonist used for induction and maintenance of general anaesthesia but paradoxically its euphoric effects lead to its classification under drugs of abuse. The serendipitous finding of rapid-onset antidepressant action of subanaesthetic dosing with ketamine by intravenous infusion has sparked many preclinical and clinical investigations...
September 2015: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Jae Lee, Puneet Narang, Manasa Enja, Steven Lippmann
Ketamine is an N-methyl-D- aspartate antagonist with rapid antidepressant effects. Research shows that ketamine has a fast onset of reduction in depressive symptoms and shows sustained remission of suicidal ideation in some patients. This article provides a brief review of the literature on the use of ketamine for depression and in acute cases of suicidality. The authors conclude that, while further investigation is needed, ketamine may be a useful treatment option for acute suicidality in emergency room settings...
January 2015: Innovations in Clinical Neuroscience
Lael Reinstatler, Nagy A Youssef
OBJECTIVE: To review the published literature on the efficacy of ketamine for the treatment of suicidal ideation (SI). METHODS: The PubMed and Cochrane databases were searched up to January 2015 for clinical trials and case reports describing therapeutic ketamine administration to patients presenting with SI/suicidality. Searches were also conducted for relevant background material regarding the pharmacological function of ketamine. RESULTS: Nine publications (six studies and three case reports) met the search criteria for assessing SI after administration of subanesthetic ketamine...
March 2015: Drugs in R&D
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