Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study

Canuso, Carla M.; Singh, Jaskaran; Fedgchin, Maggie; Alphs, Larry; Lane, Rosanne; Lim, Pilar; Pinter, Christine; Hough, David; Sanacora, Gerard; Manji, Husseini K.; Drevets, Wayne C.

doi:10.1176/appi.ajp.2018.17060720

Cited by 557 publications

(213 citation statements)

References 33 publications

Supporting

Mentioning

203

Contrasting

Unclassified

Order By: Relevance

“…Thus, this unique “5‐min administration” technique using a relatively lower dose of 0.2 mg/kg may enable widespread emergency department usage. In addition, our findings are similar to other studies conducted in the emergency department (Burger et al, ; Grunebaum et al, ; Kashani et al, ; Larkin & Beautrais, ) and are similar to the results attained for esketamine (Canuso et al, ). The unexpected lack of a statistically significant reduction in the depressive score is similar to other studies that evaluated ketamine for suicidal ideation and considered depression as a secondary outcome (Grunebaum et al, ; Murrough et al, ).…”

Section: Discussionsupporting

confidence: 92%

“…Ketamine, a glutamatergic modulator and a rapidly acting antidepressant (aan het Rot et al, 2010;Berman et al, 2000;Domany et al, 2018;Murrough et al, 2013;Singh et al, 2016;Zarate et al, 2006), has been shown to rapidly reduce suicidal ideation (Grunebaum et al, 2018;Ibrahim et al, 2011;Price, Nock, Charney, & Mathew, 2009). In addition, esketamine, the S enantiomer of racemic ketamine, has shown similar results (Canuso et al, 2018). Ketamine's antisuicidal properties raised interest in the emergency department settings, where it was evaluated in open-label trials (Larkin & Beautrais, 2011).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ketamine for acute suicidal ideation. An emergency department intervention: A randomized, double‐blind, placebo‐controlled, proof‐of‐concept trial

2019

View full text Add to dashboard Cite

Background Depressed patients presenting to emergency departments with acute suicidal ideation are a major public health concern. Ketamine, a rapidly acting antidepressant with antisuicidal properties, might offer relief. Methods In a randomized, double‐blind, placebo‐controlled, proof‐of‐concept trial, 18 depressed subjects with acute suicidal ideation, who required hospitalization, were randomized to either an intravenous ketamine 0.2 mg/kg group or a saline placebo group. Safety and efficacy evaluations were scheduled for 15, 30, 60, 90, 120, 180, and 240 min, and on Days 1, 2, 3, 7, and 14 after infusion. The main outcome measure was suicidal ideation with secondary measures of depression. Results Nine subjects were randomized to each group. There were no differences between groups at baseline in any demographic or assessment scales. A reduction in suicidal ideation was noted at 90–180 min (p < .05). Ninety minutes after infusion, 88% of the ketamine group had achieved remission of suicidal ideation compared with 33% in the placebo group (p < .05). No serious adverse events were noted. Conclusions Ketamine was safe and effective for rapid reduction in suicidal ideation in depressed, highly suicidal subjects presenting to the emergency department. Our results support further study of ketamine for acute suicidal ideation.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Ketamine for acute suicidal ideation. An emergency department intervention: A randomized, double‐blind, placebo‐controlled, proof‐of‐concept trial

2019

View full text Add to dashboard Cite

show abstract

“…It might well be that CAMS is optimal for the largest proportion of patients with a history of SI but not SA, whereas other SRB‐focused interventions are optimal among patients with a history of prior SAs. Given the focus of both CAMS and recently approved intranasal esketamine on rapid reduction in SI (Canuso et al, ), it would be of special interest to compare the separate and joint effects of these two treatments.…”

Section: Discussionmentioning

confidence: 99%

“…A number of prior studies have attempted to combine multiple interactions along the same basic lines as we do here to develop composite PTRs for treatment of major depression (reviewed by Cohen & DeRubeis, 2018). Similar efforts are also beginning to appear in studies of other mental disorders (e.g., Fernandes et al, 2017;van den Oord, Chan, & Aberg, 2018).…”

mentioning

confidence: 94%

A Preliminary Precision Treatment Rule for Remission of Suicide Ideation

Kessler

Chalker

Luedtke

et al. 2019

Suicide & Life Threat Behav

View full text Add to dashboard Cite

Objective There is growing interest in the development of composite precision treatment rules (PTRs) to guide the selection of the treatments most likely to be helpful for individual patients. We present here the results of an effort to develop a preliminary PTR for Collaborative Assessment and Management of Suicidality (CAMS) relative to enhanced‐care as usual based on secondary analysis of the Operation Worth Living (OWL) randomized controlled trial. The outcome of interest is eliminating suicide ideation (SI) within 3 months of initiating treatment. Method A state‐of‐the‐art ensemble machine learning method was used to develop the PTR among the n = 148 U.S. Soldiers (predominately male and White, age range 18–48) OWL patients. Results We estimated that CAMS was the better treatment for 77.8% of patients and that treatment assignment according to the PTR would result in a 13.6% (95% CI: 0.9%–26.3%) increase in 3‐month SI remission compared to random treatment assignment. Conclusions Although promising, results are limited by the small sample size, restrictive baseline assessment, and inability to evaluate effects on suicidal behaviors or disaggregate based on history of suicidal behaviors. Replication is needed in larger samples with comprehensive baseline assessments, longer‐term follow‐ups, and more extensive outcomes.

show abstract

“…Initial case reports (Dwyer et al, 2017) and a small open-label trial (Cullen et al, 2018) have suggested possible efficacy in pediatric populations, although there are currently no published randomized, controlled trials evaluating efficacy in pediatric populations. Recently, the FDA has approved esketamine (an intranasally delivered formulation of the l-enantiomer of ketamine) for the treatment of treatmentrefractory depression in adults (Singh et al, 2016) and initial studies have suggested that esketamine may also be effective acutely in reducing suicidal ideation (Canuso et al, 2018). Trials examining the efficacy of ketamine (NCT02579928 and NCT03889756) and esketamine (NCT03185819) in pediatric depression populations are currently ongoing.…”

Section: Interventional Treatmentsmentioning

confidence: 99%

Annual Research Review: Defining and treating pediatric treatment‐resistant depression

Dwyer

Stringaris

Brent

et al. 2020

Child Psychology Psychiatry

View full text Add to dashboard Cite

Background Adolescent major depressive disorder (MDD) is a significant health problem, associated with substantial morbidity, cost, and mortality. Depression is a significant risk factor for suicide, which is now the second leading cause of death in young people. Up to twenty per cent of adolescents will experience MDD before adulthood, and while a substantial proportion will improve with standard‐of‐care treatments (psychotherapy and medication), roughly one third will not. Methods Here, we have reviewed the literature in order to discuss the concept of treatment‐resistant depression (TRD) in adolescence, examine risk factors, diagnostic difficulties, and challenges in evaluating symptom improvement, and providing guidance on how to define adequate medication and psychotherapy treatment trials. Results We propose a staging model for adolescent TRD and review the treatment literature. The evidence base for first‐ and second‐line treatments primarily derives from four large pediatric clinical trials (TADS, TORDIA, ADAPT, and IMPACT). After two medications and a trial of evidence‐based psychotherapy have failed to alleviate depressive symptoms, the evidence becomes quite thin for subsequent treatments. Here, we review the evidence for the effectiveness of medication switches, medication augmentation, psychotherapy augmentation, and interventional treatments (i.e., transcranial magnetic stimulation, electroconvulsive therapy, and ketamine) for adolescent TRD. Comparisons are drawn to the adult TRD literature, and areas for future pediatric depression research are highlighted. Conclusions As evidence is limited for treatments in this population, a careful consideration of the known risks and side effects of escalated treatments (e.g., mood stabilizers and atypical antipsychotics) is warranted and weighed against potential, but often untested, benefits.

show abstract

Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study

Cited by 557 publications

References 33 publications

Ketamine for acute suicidal ideation. An emergency department intervention: A randomized, double‐blind, placebo‐controlled, proof‐of‐concept trial

Ketamine for acute suicidal ideation. An emergency department intervention: A randomized, double‐blind, placebo‐controlled, proof‐of‐concept trial

A Preliminary Precision Treatment Rule for Remission of Suicide Ideation

Annual Research Review: Defining and treating pediatric treatment‐resistant depression

Contact Info

Product

Resources

About