@article{534d658db449406eb9b9b40b1ee28af8,
title = "Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression",
abstract = "Background: Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine infusions resulted in a sustained antidepressant effect. In the current report, we examined the pattern and durability of antidepressant effects of repeated ketamine infusions in a larger sample, inclusive of the original. Methods: Participants with TRD (n = 24) underwent a washout of antidepressant medication followed by a series of up to six IV infusions of ketamine (.5 mg/kg) administered open-label three times weekly over a 12-day period. Participants meeting response criteria were monitored for relapse for up to 83 days from the last infusion. Results: The overall response rate at study end was 70.8%. There was a large mean decrease in Montgomery-{\AA}sberg Depression Rating Scale score at 2 hours after the first ketamine infusion (18.9 ± 6.6, p <.001), and this decrease was largely sustained for the duration of the infusion period. Response at study end was strongly predicted by response at 4 hours (94% sensitive, 71% specific). Among responders, median time to relapse after the last ketamine infusion was 18 days. Conclusions: Ketamine was associated with a rapid antidepressant effect in TRD that was predictive of a sustained effect. Future controlled studies will be required to identify strategies to maintain an antidepressant response among patients who benefit from a course of ketamine.",
keywords = "Antidepressant, experimental therapeutics, glutamate, ketamine, major depressive disorder, treatment-resistant depression",
author = "Murrough, {James W.} and Perez, {Andrew M.} and Sarah Pillemer and Jessica Stern and Parides, {Michael K.} and {Aan Het Rot}, Marije and Collins, {Katherine A.} and Mathew, {Sanjay J.} and Charney, {Dennis S.} and Iosifescu, {Dan V.}",
note = "Funding Information: The project described was supported in part by Grant UL1RR029887 from the National Center for Research Resources , National Institutes of Health (NIH), and by the Brain and Behavior Research Foundation (National Alliance for Research on Schizophrenia and Depression Distinguished Investigator Award to Dr. Charney; Young Investigator Award to Dr. Murrough). Dr. Murrough is supported by a Career Award (K23MH094707) from the National Institute of Mental Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the NIH. Funding Information: Dr. Charney, Dean of Mount Sinai School of Medicine, has been named as an inventor on a use-patent of ketamine for the treatment of depression. If ketamine were shown to be effective in the treatment of depression and received approval from the Food and Drug Administration for this indication, Dr. Charney and Mount Sinai School of Medicine could benefit financially. Within the past 2 years, Dr. Murrough completed a research fellowship at Mount Sinai School of Medicine that was supported in part by an educational grant from AstraZeneca to Mount Sinai. Dr. Iosifescu in the last 2 years has been a consultant for Central Nervous System Response. Lifetime, Dr. Iosifescu has received research support from Aspect Medical Systems, Forest Laboratories, and Janssen Pharmaceutica; he has been a consultant for Forest Laboratories, Gerson Lehrman Group, and Pfizer; and he has been a speaker for Eli Lilly and Company, Forest Laboratories, Pfizer, and Reed-Elsevier. Dr. Mathew has received research funding or salary support over the last 2 years from the Banner Family Fund, Brain and Behavior Fund, The Brown Foundation, Bristol-Myers Squibb, Department of Veterans Affairs, Evotec, Johnson and Johnson, and the National Institute of Mental Health (5R01MH81870). He has received consulting fees or honoraria from Allergan, AstraZeneca, Cephalon, Corcept, Roche, and Takeda and has received medication from Sanofi-Aventis for an NIH-sponsored study. Dr. Mathew has been named as an inventor on a use patent of ketamine for the treatment of depression. Dr. Mathew has relinquished his claim to any royalties and will not benefit financially if ketamine were approved for this use. Drs. Perez, Parides and aan het Rot and Ms. Pillemer, Stern, and Collins reported no biomedical financial interests or potential conflicts of interest. ",
year = "2013",
month = aug,
day = "15",
doi = "10.1016/j.biopsych.2012.06.022",
language = "English (US)",
volume = "74",
pages = "250--256",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "4",
}