TY - JOUR
T1 - Time to relapse after a single administration of intravenous ketamine augmentation in unipolar treatment-resistant depression
AU - Salloum, Naji C.
AU - Fava, Maurizio
AU - Hock, Rebecca S.
AU - Freeman, Marlene P.
AU - Flynn, Martina
AU - Hoeppner, Bettina
AU - Cusin, Cristina
AU - Iosifescu, Dan V.
AU - Trivedi, Madhukar H.
AU - Sanacora, Gerard
AU - Mathew, Sanjay J.
AU - Debattista, Charles
AU - Ionescu, Dawn F.
AU - Papakostas, George I.
N1 - Funding Information:
Charles Debattista: Dr. DeBattista has received grant support from Janssen, Neuronetics, St. Jude, and Biolite. He has served on the Advisory Board of Alkermes.
Funding Information:
Cristina Cusin: Research: from NIMH (R01MH102279); consulting fees: from Janssen Pharmaceuticals, Takeda, Boehringer, Lundbeck. She has also participated in research funded by Janssen, Medtronic, Otsuka, Takeda.
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, MD and George Papakostas, co-principal investigators). 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 U.S. Government. We would like to thank Drs. Mi Hillefors, Steven Zalcman, Adam Haim, and Galia Siegel from NIMH, for their support, which was absolutely critical to both the planning and the implementation of the study.
Funding Information:
Dawn F. Ionescu: Presently an employee of Janssen Pharmaceuticals Research & Development, La Jolla, CA. Research grants: from NARSAD, AFSP.
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Objective: To examine the rate and time to relapse for remitters and responders to ketamine in treatment-resistant depression (TRD). Methods: Subjects with TRD were randomized to a single infusion of one of several doses of intravenous ketamine, or midazolam. Using Kaplan-Meier survival function, the current report examines the rate and time to relapse, defined as MADRS ≥ 22, over a period of 30 days, in subjects who achieved remission (MADRS ≤ 10) or response (≥ 50% reduction in MADRS) on day three post-infusion of intravenous ketamine 0.1, 0.5, or 1.0 mg/kg. Results: Of the 60 randomized participants who received a single ketamine (0.1, 0.5, or 1.0 mg/kg) infusion, 19 (34%) met criteria for remission and 27 (48%) for response, on day 3 post-infusion. A numerical dose-response relationship was observed, with remitters/responders on ketamine 1.0 mg/kg having the lowest relapse rate, followed by ketamine 0.5 mg/kg and 0.1 mg/kg, respectively (% of remitters who relapsed by day 14: 38% with 1.0 mg/kg, 50% with 0.5 mg/kg, 100% with 0.1 mg/kg;% of responders who relapsed by day 14: 30% with 1.0 mg/kg, 50% with 0.5 mg/kg, 80% with 0.1 mg/kg). Limitations: The sample size was small. No MADRS measurements at day one post-infusion. The study was not powered to assess differences in relapse prevention between different doses of ketamine. Conclusion: Time to relapse after successful treatment with a single infusion of ketamine appears to follow a dose-response relationship, where higher dosage leads to increased time to relapse.
AB - Objective: To examine the rate and time to relapse for remitters and responders to ketamine in treatment-resistant depression (TRD). Methods: Subjects with TRD were randomized to a single infusion of one of several doses of intravenous ketamine, or midazolam. Using Kaplan-Meier survival function, the current report examines the rate and time to relapse, defined as MADRS ≥ 22, over a period of 30 days, in subjects who achieved remission (MADRS ≤ 10) or response (≥ 50% reduction in MADRS) on day three post-infusion of intravenous ketamine 0.1, 0.5, or 1.0 mg/kg. Results: Of the 60 randomized participants who received a single ketamine (0.1, 0.5, or 1.0 mg/kg) infusion, 19 (34%) met criteria for remission and 27 (48%) for response, on day 3 post-infusion. A numerical dose-response relationship was observed, with remitters/responders on ketamine 1.0 mg/kg having the lowest relapse rate, followed by ketamine 0.5 mg/kg and 0.1 mg/kg, respectively (% of remitters who relapsed by day 14: 38% with 1.0 mg/kg, 50% with 0.5 mg/kg, 100% with 0.1 mg/kg;% of responders who relapsed by day 14: 30% with 1.0 mg/kg, 50% with 0.5 mg/kg, 80% with 0.1 mg/kg). Limitations: The sample size was small. No MADRS measurements at day one post-infusion. The study was not powered to assess differences in relapse prevention between different doses of ketamine. Conclusion: Time to relapse after successful treatment with a single infusion of ketamine appears to follow a dose-response relationship, where higher dosage leads to increased time to relapse.
KW - Ketamine
KW - Major depressive disorder
KW - Relapse
KW - Remission
KW - Treatment-resistant depression
UR - http://www.scopus.com/inward/record.url?scp=85071728685&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071728685&partnerID=8YFLogxK
U2 - 10.1016/j.jad.2019.09.017
DO - 10.1016/j.jad.2019.09.017
M3 - Article
C2 - 31494365
AN - SCOPUS:85071728685
SN - 0165-0327
VL - 260
SP - 131
EP - 139
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
ER -