Molecular Psychiatry
June 25, 2026
Clotilde Guidetti, Maurizio Fava, George I. Papakostas
Major depressive disorder (MDD) and treatment-resistant depression (TRD) are prevalent and debilitating conditions. Over 50% of patients have inadequate response to first-line serotonergic antidepressants and are left with suboptimal treatment options. Rapid-acting and individually tailored treatments for MDD remain major unmet needs. This review discusses promising rapid-acting treatments,...
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...
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...
Molecular Psychiatry
September 7, 2022
Rebecca B Price, Nicholas Kissel, Andrew Baumeister et al.
80 citations
Abstract Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar...
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,...
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...
The Journal of Clinical Psychiatry
May 26, 2020
George I. Papakostas, Naji C. Salloum, Rebecca S. Hock et al.
107 citations
OBJECTIVE: Esketamine, the S-enantiomer of ketamine, was recently approved as a rapid-acting intranasal therapy for depression and is currently under development for suicidality. The authors sought to determine the efficacy of adjunctive intranasal esketamine in major depressive disorder (MDD). DATA SOURCES: A systematic search of PubMed/MEDLINE was conducted up to January 2019, in addition to...
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...
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...
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...
Current behavioral neuroscience reports
June 1, 2016
Dawn F. Ionescu, George I. Papakostas
Traditional antidepressant medications generally take weeks-to-months to achieve effect. However, the breakthrough finding of ketamine's rapidly acting antidepressant properties has inspired a decade-and-a-half of progress towards the identification of treatments that work quickly-within hours-to-days. This paradigm-shift in the discovery of antidepressant therapies has significantly changed...