Improvement in suicidal ideation after ketamine infusion: Relationship to reductions in depression and anxiety

Ballard, Elizabeth D.; Ionescu, Dawn F.; Voort, Jennifer L. Vande; Niciu, Mark J.; Richards, Erica M.; Luckenbaugh, David A.; Brutsché, Nancy E.; Ameli, Rezvan; Furey, Maura L.; Zarate, Carlos A.

doi:10.1016/j.jpsychires.2014.07.027

Cited by 243 publications

(156 citation statements)

References 48 publications

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“…119 It also reduces suicidal thoughts within hours, mostly but not entirely due to reductions in depressive symptoms. 120 One RCT using an active placebo (midazolam) showed that 53% of patients treated with ketamine scored 0 on three different measures of suicidal ideation 24 hours after infusion compared with 24% of those treated with midazolam (P=0.03). 121 The reductions in conscious suicidal thoughts were also observed unconsciously through IAT testing.…”

Section: Self Poisoningmentioning

confidence: 99%

Suicide risk assessment and intervention in people with mental illness

Bolton

Gunnell

Turecki

2015

BMJ

243

188

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Suicide is the 15th most common cause of death worldwide. Although relatively uncommon in the general population, suicide rates are much higher in people with mental health problems. Clinicians often have to assess and manage suicide risk. Risk assessment is challenging for several reasons, not least because conventional approaches to risk assessment rely on patient self reporting and suicidal patients may wish to conceal their plans. Accurate methods of predicting suicide therefore remain elusive and are actively being studied. Novel approaches to risk assessment have shown promise, including empirically derived tools and implicit association tests. Service provision for suicidal patients is often substandard, particularly at times of highest need, such as after discharge from hospital or the emergency department. Although several drug based and psychotherapy based treatments exist, the best approaches to reducing the risk of suicide are still unclear. Some of the most compelling evidence supports long established treatments such as lithium and cognitive behavioral therapy. Emerging options include ketamine and internet based psychotherapies. This review summarizes the current science in suicide risk assessment and provides an overview of the interventions shown to reduce the risk of suicide, with a focus on the clinical management of people with mental disorders.

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Section: Self Poisoningmentioning

confidence: 99%

Suicide risk assessment and intervention in people with mental illness

Bolton

Gunnell

Turecki

2015

BMJ

243

188

View full text Add to dashboard Cite

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“…However, it is not clear that any other more selective NMDA receptor antagonist tested in the clinic produces comparable or improved efficacy as has been demonstrated with ketamine (Sanacora and Schatzberg, 2015). Despite the psychomimetic effects and cognitive impairment that may be produced within the first 30-45 minutes following ketamine administration, the clinical use of ketamine in depressed patients does appear to decrease suicidality (DiazGranados et al, 2010;Zarate et al, 2012;Ballard et al, 2014;Price et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

The Utility of Impulsive Bias and Altered Decision Making as Predictors of Drug Efficacy and Target Selection: Rethinking Behavioral Screening for Antidepressant Drugs

Marek

Day

Hudzik

2015

Journal of Pharmacology and Experimental Therapeutics

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Cognitive dysfunction may be a core feature of major depressive disorder, including affective processing bias, abnormal response to negative feedback, changes in decision making, and increased impulsivity. Accordingly, a translational medicine paradigm predicts clinical action of novel antidepressants by examining drug-induced changes in affective processing bias. With some exceptions, these concepts have not been systematically applied to preclinical models to test new chemical entities. The purpose of this review is to examine whether an empirically derived behavioral screen for antidepressant drugs may screen for compounds, at least in part, by modulating an impulsive biasing of responding and altered decision making. The differential-reinforcement-of-low-rate (DRL) 72-second schedule is an operant schedule with a documented fidelity for discriminating antidepressant drugs from nonantidepressant drugs. However, a theoretical basis for this empirical relationship has been lacking. Therefore, this review will discuss whether response bias toward impulsive behavior may be a critical screening characteristic of DRL behavior requiring long interresponse times to obtain rewards. This review will compare and contrast DRL behavior with the five-choice serial reaction time task, a test specifically designed for assessing motoric impulsivity, with respect to psychopharmacological testing and the neural basis of distributed macrocircuits underlying these tasks. This comparison suggests that the existing empirical basis for the DRL 72-second schedule as a pharmacological screen for antidepressant drugs is complemented by a novel hypothesis that altering impulsive response bias for rodents trained on this operant schedule is a previously unrecognized theoretical cornerstone for this screening paradigm.

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“…In addition to the more explicit reduction of suicidal thinking, the Implicit Association Test, an assessment of suicidal cognition and potential predictor of future suicidal behavior, has been studied in the context of ketamine infusion, which has also revealed reductions in implicit suicidal thinking [Price et al 2009[Price et al , 2014. Our group recently published a secondary data analysis of 108 patients with treatment-resistant major depression (both MDD and BDep) who received a single subanesthetic dose infusion of ketamine to study the relationship between improvements in depression/anxiety and suicidality; in this sample, improvements in suicidal thinking were partially related to improvements in neuropsychiatric symptoms, explaining up to 20% of the antisuicidal effect [Ballard et al 2014]. Interestingly, in another secondary analysis of the same sample, a lack of a lifetime history of suicide attempt predicted improved antidepressant response to ketamine at 1 week post infusion [Niciu et al 2014b].…”

Section: Antisuicidal Effectsmentioning

confidence: 99%

Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review

Iadarola

Niciu

Richards

et al. 2015

Therapeutic Advances in Chronic Disease

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181

117

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Current pharmacotherapies for major depressive disorder (MDD) and bipolar depression (BDep) have a distinct lag of onset that can generate great distress and impairment in patients. Furthermore, as demonstrated by several real-world effectiveness trials, their efficacy is limited. All approved antidepressant medications for MDD primarily act through monoaminergic mechanisms, agonists or antagonists with varying affinities for serotonin, norepinephrine and dopamine. The glutamate system has received much attention in recent years as an avenue for developing novel therapeutics. A single subanesthetic dose infusion of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has been shown to have rapid and potent antidepressant effects in treatment-resistant MDD and BDep. In a reverse translational framework, ketamine's clinical efficacy has inspired many preclinical studies to explore glutamatergic mechanisms of antidepressant action. These studies have revealed enhanced synaptic plasticity/synaptogenesis via numerous molecular and cellular mechanisms: release of local translational inhibition of brain-derived neurotrophic factor and secretion from dendritic spines, mammalian target of rapamycin activation and glycogen synthase kinase-3 inhibition. Current efforts are focused on extending ketamine's antidepressant efficacy, uncovering the neurobiological mechanisms responsible for ketamine's antidepressant activity in biologically enriched subgroups, and identifying treatment response biomarkers to personalize antidepressant selection. Other NMDA receptor antagonists have been studied both preclinically and clinically, which have revealed relatively modest antidepressant effects compared with ketamine but potentially other favorable characteristics, for example, decreased dissociative or psychotomimetic effects; therefore, there is great interest in developing novel glutamatergic antidepressants with greater target specificity and/or decreased adverse effects.

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Improvement in suicidal ideation after ketamine infusion: Relationship to reductions in depression and anxiety

Cited by 243 publications

References 48 publications

Suicide risk assessment and intervention in people with mental illness

Suicide risk assessment and intervention in people with mental illness

The Utility of Impulsive Bias and Altered Decision Making as Predictors of Drug Efficacy and Target Selection: Rethinking Behavioral Screening for Antidepressant Drugs

Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review

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