TY - JOUR
T1 - The effect of single administration of intravenous ketamine augmentation on suicidal ideation in treatment-resistant unipolar depression
T2 - Results from a randomized double-blind study
AU - Feeney, Anna
AU - Hock, Rebecca S.
AU - Freeman, Marlene P.
AU - Flynn, Martina
AU - Hoeppner, Bettina
AU - Iosifescu, Dan V.
AU - Trivedi, Madhukar H.
AU - Sanacora, Gerard
AU - Mathew, Sanjay J.
AU - Debattista, Charles
AU - Ionescu, Dawn F.
AU - Fava, Maurizio
AU - Papakostas, George I.
N1 - Funding Information:
Research Support: Abbott Laboratories; Acadia Pharmaceuticals; Alkermes, Inc.; American Cyanamid; Aspect Medical Systems; AstraZeneca; Avanir Pharmaceuticals; AXSOME Therapeutics; BioClinica, Inc; Biohaven; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon; Cerecor; Clarus Funds; Clexio Biosciences; Clintara, LLC; Covance; Covidien; Eli Lilly and Company;EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; FORUM Pharmaceuticals; Ganeden Biotech, Inc.; Gentelon, LLC; GlaxoSmithKline; Harvard Clinical Research Institute; Hoffman-LaRoche; Icon Clinical Research; Indivior; i3 Innovus/Ingenix; Janssen R&D, LLC; Jed Foundation; Johnson & Johnson Pharmaceutical Research & Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Lundbeck Inc.; Marinus Pharmaceuticals; MedAvante; Methylation Sciences Inc; National Alliance for Research on Schizophrenia & Depression (NARSAD); National Center for Complementary and Alternative Medicine (NCCAM); National Coordinating Center for Integrated Medicine (NiiCM); National Institute of Drug Abuse (NIDA); National Institutes of Health; National Institute of Mental Health (NIMH); Neuralstem, Inc.; NeuroRx; Novartis AG; Organon Pharmaceuticals; Otsuka Pharmaceutical Development, Inc.; PamLab, LLC.; Pfizer Inc.; Pharmacia-Upjohn; Pharmaceutical Research Associates., Inc.; Pharmavite® LLC; PharmoRx Therapeutics; Photothera; Premiere Research International; Reckitt Benckiser; Roche Pharmaceuticals; RCT Logic, LLC (formerly Clinical Trials Solutions, LLC); Sanofi-Aventis US LLC; Shenox Pharmaceuticals, LLC; Shire; Solvay Pharmaceuticals, Inc.; Stanley Medical Research Institute (SMRI); Synthelabo; Taisho Pharmaceuticals; Takeda Pharmaceuticals; Tal Medical; VistaGen; Wyeth-Ayerst Laboratories
Funding Information:
Madhukar H. Trivedi: Within the past 12 months, Dr. Trivedi has provided consulting services to Acadia Pharmaceuticals, Inc., Allergan, Inc., Alto Neuroscience Inc, Axsome Therapeutics, Engage Health Media, GreenLight VitalSign6 Inc, Janssen, Merck Sharp & Dohme Corp., Myriad Neuroscience, Navitor Pharmaceutical Inc, Otsuka, Perception Neuroscience, SAGE Therapeutics, and Signant Health. He has received grant/research funding from NIMH, NIDA, Patient-Centered Outcomes Research Institute (PCORI), and Cancer Prevention Research Institute of Texas (CPRIT). Additionally, he has received editorial compensation from Oxford University Press.
Funding Information:
This project was funded by the National Institute of Mental Health (NIMH) under Contract Rapidly-Acting Treatments for Treatment-Resistant Depression (RAPID) Number: HHSN271201100006I, to the Massachusetts General Hospital (Maurizio Fava and George Papakostas, co-principal investigators). The NIMH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.
Publisher Copyright:
© 2021
PY - 2021/8
Y1 - 2021/8
N2 - 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, 7, 14 and 30 days post infusion. Clinically significant suicidal ideation was defined as a MADRS suicide item score ≥2. Forty patients who received IV ketamine and 16 who received IV midazolam had suicide item scores of ≥2 at baseline (IV ketamine group mean 2.90±0.74; IV midazolam group 2.69±0.70). The mean suicide scores of these groups differed significantly from each other on day 30; the IV ketamine group had a lower mean score than controls (2.03±1.59 vs. 3.00±1.41, t-test p = 0.049; Hedges’ g 0.71). Among patients with a suicide score of ≥2 at baseline and <2 at day 3, the two groups did not differ significantly on mean scores changes at days 3, 5, 7, 14 or 30. Recurrence of suicidal ideation was extensive in both treatment groups. A single infusion of IV ketamine may reduce suicidal ideation in TRD out to 30 days post infusion, but early anti-suicidal effects appear to diminish rapidly. This post-hoc analysis was not powered to compare different doses of ketamine. A single infusion of IV ketamine might have a role as an adjunct to standard treatments in patients with TRD and suicidal ideation. Trial registration: NCT01920555.
AB - 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, 7, 14 and 30 days post infusion. Clinically significant suicidal ideation was defined as a MADRS suicide item score ≥2. Forty patients who received IV ketamine and 16 who received IV midazolam had suicide item scores of ≥2 at baseline (IV ketamine group mean 2.90±0.74; IV midazolam group 2.69±0.70). The mean suicide scores of these groups differed significantly from each other on day 30; the IV ketamine group had a lower mean score than controls (2.03±1.59 vs. 3.00±1.41, t-test p = 0.049; Hedges’ g 0.71). Among patients with a suicide score of ≥2 at baseline and <2 at day 3, the two groups did not differ significantly on mean scores changes at days 3, 5, 7, 14 or 30. Recurrence of suicidal ideation was extensive in both treatment groups. A single infusion of IV ketamine may reduce suicidal ideation in TRD out to 30 days post infusion, but early anti-suicidal effects appear to diminish rapidly. This post-hoc analysis was not powered to compare different doses of ketamine. A single infusion of IV ketamine might have a role as an adjunct to standard treatments in patients with TRD and suicidal ideation. Trial registration: NCT01920555.
KW - Antidepressant drugs
KW - Depressive disorder, major
KW - Depressive disorder, treatment resistant
KW - Ketamine
KW - Suicidal ideation
UR - http://www.scopus.com/inward/record.url?scp=85107669118&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85107669118&partnerID=8YFLogxK
U2 - 10.1016/j.euroneuro.2021.04.024
DO - 10.1016/j.euroneuro.2021.04.024
M3 - Article
C2 - 34090255
AN - SCOPUS:85107669118
VL - 49
SP - 122
EP - 132
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
SN - 0924-977X
ER -