Journal
BIOLOGICAL PSYCHIATRY
Volume 74, Issue 4, Pages 250-256Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2012.06.022
Keywords
Antidepressant; experimental therapeutics; glutamate; ketamine; major depressive disorder; treatment-resistant depression
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Funding
- Mount Sinai School of Medicine
- AstraZeneca
- Aspect Medical Systems
- Forest Laboratories
- Janssen Pharmaceutica
- Banner Family Fund
- Brain and Behavior Fund
- Brown Foundation
- Bristol-Myers Squibb
- Department of Veterans Affairs
- Evotec
- Johnson and Johnson
- National Institute of Mental Health [5R01MH81870]
- Allergan
- Cephalon
- Corcept
- Roche
- Takeda
- NIH
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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-Asberg 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.
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