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Biol Psychiatry. 2013 Aug 15;74(4):250-6. doi: 10.1016/j.biopsych.2012.06.022. Epub 2012 Jul 27.

Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression.

Author information

1
Mood and Anxiety Disorders Program, Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA. james.murrough@mssm.edu

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

PMID:
22840761
PMCID:
PMC3725185
DOI:
10.1016/j.biopsych.2012.06.022
[Indexed for MEDLINE]
Free PMC Article
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