Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression
James W Murrough, Andrew M Perez, Sarah Pillemer, Jessica Stern, Michael K Parides, Marije aan het Rot, Katherine A Collins, Sanjay J Mathew, Dennis S Charney, Dan V Iosifescu, James W Murrough, Andrew M Perez, Sarah Pillemer, Jessica Stern, Michael K Parides, Marije aan het Rot, Katherine A Collins, Sanjay J Mathew, Dennis S Charney, Dan V Iosifescu
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-Åsberg 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.
Trial registration: ClinicalTrials.gov NCT00548964.
Keywords: Antidepressant; experimental therapeutics; glutamate; ketamine; major depressive disorder; treatment-resistant depression.
Conflict of interest statement
DISCLOSURE:
Drs. Perez, Parides and aan het Rot and Ms. Pillemer, Stern and Collins reported no biomedical financial interests or potential conflicts of interest.
Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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Source: PubMed