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Gerard Sanacora

Yale University, Yale New Haven Hospital

58 papers in the library · 8,866 citations · publishing 2011-2026

Papers

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Effect of Concomitant Benzodiazepines on the Antidepressant Effects of Ketamine

The Journal of Clinical Psychiatry November 14, 2022 Anna Feeney, Bettina B. Hoeppner, Marlene P. Freeman et al. 9 citations

Objective: Ketamine is a novel and rapidly acting treatment for major depressive disorder (MDD). Benzodiazepines are commonly coprescribed with antidepressants in MDD. This study sought to examine data from a randomized clinical trial that compared a single infusion of intravenous (IV) ketamine to midazolam placebo in treatment-resistant depression (DSM-IV-TR MDD) and to assess whether the use...

Efficacy and Safety of Ketamine vs Electroconvulsive Therapy Among Patients With Major Depressive Episode: A Systematic Review and Meta-analysis.

JAMA Psychiatry October 19, 2022 T. Rhee, S. Shim, B. Forester et al. 139 citations

Importance Whether ketamine is as effective as electroconvulsive therapy (ECT) among patients with major depressive episode remains unknown. Objective To systematically review and meta-analyze data about clinical efficacy and safety for ketamine and ECT in patients with major depressive episode. Data Sources PubMed, MEDLINE, Cochrane Library, and Embase were systematically searched using...

Treatment response to esketamine nasal spray in patients with major depressive disorder and acute suicidal ideation or behavior without evidence of early response: a pooled post hoc analysis of ASPIRE

CNS Spectrums July 29, 2022 Ibrahim Turkoz, Oliver Lopena, Giacomo Salvadore et al. 6 citations

Abstract Objective To assess the likelihood of attaining response/remission of depressive symptoms with esketamine nasal spray (ESK) plus standard of care (SoC) vs placebo nasal spray (PBO) plus SoC at 4 weeks in patients with major depressive disorder and active suicidal ideation with intent (MDSI) without early response. Methods A post hoc analysis of pooled data from ASPIRE I and ASPIRE II...

Evaluation of the Trajectory of Depression Severity With Ketamine and Esketamine Treatment in a Clinical Setting

JAMA Psychiatry May 11, 2022 Sina Nikayin, Taeho Greg Rhee, Maria Elena Cunningham et al. 43 citations

This comparative analysis examines the trajectory of depression severity among patients treated with intravenous ketamine or intranasal esketamine in a clinical setting.

Efficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam-Controlled Trial

FOCUS The Journal of Lifelong Learning in Psychiatry April 1, 2022 Jennifer B. Dwyer, Angeli Landeros‐Weisenberger, Jessica A. Johnson et al. 51 citations

Objective: Adolescent depression is prevalent and is associated with significant morbidity and mortality. Although intravenous ketamine has shown efficacy in adult treatment-resistant depression, its efficacy in pediatric populations is unknown. The authors conducted an active-placebo-controlled study of ketamine's safety and efficacy in adolescents. Methods: In this proof-of-concept...

Ketamine in the Treatment of Obsessive-Compulsive Disorder: A Systematic Review

Harvard Review of Psychiatry March 1, 2022 Igor D. Bandeira, Daniel H Lins-Silva, Vitor Breseghello Cavenaghi et al. 35 citations

INTRODUCTION: First-line treatment for obsessive-compulsive disorder (OCD) includes exposure and response prevention behavioral therapy and serotonin reuptake inhibitors, particularly in combination. New and more effective treatments are needed, give that recent studies suggest that glutamatergic neurotransmission contributes to the pathophysiology of the disorder. In these circumstances,...

mTORC1 inhibitor effects on rapid ketamine-induced reductions in suicidal ideation in patients with treatment-resistant depression.

Journal of Affective Disorders 2022 L. Averill, C. Averill, R. Gueorguieva et al.

Suicide is a public health crisis with limited treatment options. Ketamine has demonstrated rapid and robust improvements in suicidal ideation (SI). The parent study for the secondary pilot analyses presented here was a double-blind, cross-over trial that found pretreatment with the mechanistic target of rapamycin complex 1 (mTORC1) prolonged the antidepressant effects of ketamine. Here we...

The effect of single administration of intravenous ketamine augmentation on suicidal ideation in treatment-resistant unipolar depression: results from a randomized double-blind study

European Neuropsychopharmacology June 2, 2021 A. Feeney, Rebecca S. Hock, Marlene P. Freeman et al. 33 citations

This study aimed to assess the effect of a single infusion of intravenous (IV) ketamine on suicidal ideation in patients with treatment-resistant depression (TRD). Patients with TRD were randomized in a double-blind fashion to a single infusion of IV ketamine or IV midazolam placebo. Suicidal ideation was measured using the Montgomery-Asberg Depression Rating Scale (MADRS) suicide item at 3, 5,...

Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation

American Journal of Psychiatry March 17, 2021 Roger S McIntyre, Joshua D. Rosenblat, Charles B. Nemeroff et al. 694 citations

Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based antidepressants in major depression, the majority of treated individuals fail to achieve full syndromal and functional recovery with the index and subsequent pharmacological treatments. Ketamine and esketamine represent...

Efficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam-Controlled Trial.

American Journal of Psychiatry March 3, 2021 J. Dwyer, Angeli Landeros‐Weisenberger, Jessica A. Johnson et al. 163 citations

OBJECTIVE Adolescent depression is prevalent and is associated with significant morbidity and mortality. Although intravenous ketamine has shown efficacy in adult treatment-resistant depression, its efficacy in pediatric populations is unknown. The authors conducted an active-placebo-controlled study of ketamine's safety and efficacy in adolescents. METHODS In this proof-of-concept randomized,...

Cognitive Behavioral Therapy to Sustain the Antidepressant Effects of Ketamine in Treatment-Resistant Depression: A Randomized Clinical Trial

Psychotherapy and Psychosomatics 2021 Samuel t. Wilkinson, Taeho greg Rhee, Jutta Joormann et al. 102 citations

<b><i>Introduction:</i></b> Ketamine has emerged as a rapid-acting antidepressant. While ongoing treatment can prevent relapse, concerns exist regarding long-term exposure. <b><i>Objective:</i></b> We conducted a randomized trial to examine the feasibility and efficacy of cognitive behavioral therapy (CBT) following intravenous ketamine in treatment-resistant depression (TRD)....

Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation With Intent

The Journal of Clinical Psychiatry May 11, 2020 Dong-Jing Fu, Dawn F. Ionescu, Xiang Li et al. 367 citations

OBJECTIVE: To compare esketamine to placebo, each in addition to standard-of-care treatment, for rapidly reducing major depressive disorder symptoms, including suicidal ideation. METHODS: This phase 3, double-blind, multicenter study (ASPIRE I), conducted between June 2017 and December 2018, enrolled 226 adults having major depressive disorder based on Diagnostic and Statistical Manual of...

Body Mass Index as a Moderator of Treatment Response to Ketamine for Major Depressive Disorder

Journal of Clinical Psychopharmacology April 25, 2020 Marlene P. Freeman, Rebecca S. Hock, George I. Papakostas et al. 45 citations

PURPOSE/BACKGROUND: Major depressive disorder (MDD) and obesity commonly co-occur. We sought to assess the impact of body mass index (BMI) on the acute antidepressant effects of ketamine in patients with treatment-resistant depression. METHODS/PROCEDURES: Post hoc analyses were conducted from a multisite, randomized, double-blind, placebo-controlled trial designed to assess the rapid-onset...

Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression

The Journal of Clinical Psychiatry April 20, 2020 Ewa Wajs, Leah Aluisio, Richard Holder et al. 288 citations

OBJECTIVE: To evaluate long-term safety and efficacy of esketamine nasal spray plus a new oral antidepressant (OAD) in patients with treatment-resistant depression (TRD). METHODS: This phase 3, open-label, multicenter, long-term (up to 1 year) study was conducted between October 2015 and October 2017. Patients (≥ 18 years) with TRD (DSM-5 diagnosis of major depressive disorder and nonresponse...

Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin

Neuropsychopharmacology February 24, 2020 Chadi G. Abdallah, Lynnette A. Averill, Ralitza Gueorguieva et al. 181 citations

Twenty-four hours after administration, ketamine exerts rapid and robust antidepressant effects that are thought to be mediated by activation of the mechanistic target of rapamycin complex 1 (mTORC1). To test this hypothesis, depressed patients were pretreated with rapamycin, an mTORC1 inhibitor, prior to receiving ketamine. Twenty patients suffering a major depressive episode were randomized...

Intravenous arketamine for treatment-resistant depression: open-label pilot study

European Archives of Psychiatry and Clinical Neuroscience February 20, 2020 Gustavo C. Leal, Igor D. Bandeira, Fernanda S. Correia-Melo et al. 257 citations

We aimed to analyze the efficacy and safety of arketamine, the R (−)-enantiomer of ketamine, for treatment-resistant depression (TRD) in humans. Open-label pilot trial, seven subjects with TRD received a single intravenous infusion of arketamine (0.5 mg/kg); primary outcome was change in Montgomery–Åsberg Depression Rating Scale (MADRS) 24 h after. Mean MADRS dropped from 30.7 before infusion...

Ketamine: a paradigm shift for depression research and treatment

Neuron March 1, 2019 John H. Krystal, Chadi G. Abdallah, Gerard Sanacora et al. 443 citations

Ketamine is the first exemplar of a rapid-acting antidepressant with efficacy for treatment-resistant symptoms of mood disorders. Its discovery emerged from a reconceptualization of the biology of depression. Neurobiological insights into ketamine efficacy shed new light on the mechanisms underlying antidepressant efficacy. The rapid, profound, and sustainable antidepressant effects of ketamine...

ELEctroconvulsive therapy (ECT) vs. Ketamine in patients with Treatment-resistant Depression: The ELEKT-D study protocol.

Contemporary Clinical Trials February 1, 2019 S. Mathew, S. Wilkinson, Murat Altinay et al. 54 citations

Major depressive disorder (MDD) is the most common mental illness and the leading cause of disability worldwide. Electroconvulsive therapy (ECT) is the most effective treatment for MDD and the gold-standard therapy for treatment-resistant depression (TRD), yet it remains underutilized due to factors such as limited availability, stigma, and concerns about cognitive side effects. Ketamine has...

Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment-resistant depression

Depression and Anxiety December 30, 2018 Naji C. Salloum, Maurizio Fava, Marlene P. Freeman et al. 49 citations

OBJECTIVE: To examine the effect of high baseline anxiety on response to ketamine versus midazolam (active placebo) in treatment-resistant depression (TRD). METHODS: In a multisite, double-blind, placebo-controlled trial, 99 subjects with TRD were randomized to one of five arms: a single dose of intravenous ketamine 0.1, 0.2, 0.5, 1.0 mg/kg, or midazolam 0.045 mg/kg. The primary outcome measure...

Double-Blind, Placebo-Controlled, Dose-Ranging Trial of Intravenous Ketamine as Adjunctive Therapy in Treatment-Resistant Depression (TRD)

Molecular Psychiatry October 3, 2018 Maurizio Fava, M. Freeman, M. Flynn et al. 438 citations

Numerous placebo-controlled studies have demonstrated the ability of ketamine, an NMDA receptor antagonist, to induce rapid (within hours), transient antidepressant effects when administered intravenously (IV) at subanesthetic doses (0.5 mg/kg over 40 min). However, the optimal antidepressant dose remains unknown. We aimed to compare to active placebo the rapid acting antidepressant properties...

Acute and Longer-Term Outcomes Using Ketamine as a Clinical Treatment at the Yale Psychiatric Hospital

The Journal of Clinical Psychiatry July 23, 2018 Samuel T. Wilkinson, Rachel B. Katz, Mesut Toprak et al. 88 citations

OBJECTIVE: Ketamine has emerged as a rapid-acting antidepressant, though controversy remains whether sufficient data exist to justify its use outside of research protocols. In October 2014, the authors' institution began providing ketamine as an off-label therapy on a case-by-case basis for patients unable to participate in research protocols. Here, the participant experience during 29 months...

Ketamine: A Review for Clinicians

FOCUS The Journal of Lifelong Learning in Psychiatry July 1, 2018 Gerard Sanacora, Rachel B. Katz 16 citations

A growing series of clinical trials and case series now suggest that ketamine-originally used as an anesthetic agent-potentially offers an exciting new treatment option for severe depression. Increasing numbers of studies show that ketamine can provide prompt relief for many depressed patients, including those with severe treatment-refractory depression. Although the effects of a single...

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

American Journal of Psychiatry April 16, 2018 Carla M. Canuso, Jaskaran Singh, Maggie Fedgchin et al. 666 citations

OBJECTIVE: The authors compared the efficacy of standard-of-care treatment plus intranasal esketamine or placebo for rapid reduction of symptoms of major depression, including suicidality, among individuals at imminent suicide risk. METHOD: In a double-blind, multicenter, proof-of-concept study, 68 participants were randomly assigned to receive esketamine (84 mg) or placebo twice weekly for 4...

The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis

American Journal of Psychiatry October 3, 2017 S. Wilkinson, Elizabeth D. Ballard, Michael H. Bloch et al. 680 citations

Objective Suicide is a public health crisis with limited treatment options. We conducted a systematic review and individual participant data meta-analysis examining the effects of a single dose of ketamine on suicidal ideation. Method Individual participant data were obtained from 10 of 11 identified comparison intervention studies (using either saline or midazolam as control). The analysis...

Considerations on the Off-label Use of Ketamine as a Treatment for Mood Disorders

JAMA August 14, 2017 Samuel T. Wilkinson, Gerard Sanacora 36 citations

This Viewpoint summarizes a number of important issues related to the clinical use of ketamine for the treatment of psychiatric disorders addressed in the consensus statement and provides suggestions for addressing remaining concerns.