Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression
This open-label study (n=24) found that repeated infusions of ketamine can sustain the rapid anti-depressant effect obtained after one infusion. Nevertheless, the effect of 6 infusions was only maintained for a median of 18 days.
Authors
- Sanjay Mathew
- James Murrough
- Dennis Charney
Published
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.
Research Summary of 'Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression'
Introduction
Major depressive disorder (MDD) causes substantial morbidity and societal cost in part because many patients do not respond adequately to existing antidepressant treatments. Earlier clinical research has shown that the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine can produce rapid antidepressant effects, including in individuals with treatment-resistant depression (TRD). Most trials have focused on a single low-dose (.5 mg/kg) intravenous infusion and report rapid but often short-lived benefit, leaving a clinical need to identify strategies that extend or maintain ketamine's antidepressant effects. Murrough and colleagues designed the present study to characterise the time course and durability of antidepressant effects when ketamine is given repeatedly. Using an open-label regimen of up to six IV ketamine infusions administered three times weekly over 12 days, the investigators aimed to: quantify the overall response rate; determine when the largest symptom change occurs; compare symptom trajectories between responders and nonresponders; estimate time to relapse after stopping infusions; and examine ketamine's effect on individual depressive symptoms in a larger sample than their prior report.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Murrough, J. W., Perez, A. M., Pillemer, S., Stern, J., Parides, M. K., aan het Rot, M., Collins, K. A., Mathew, S. J., Charney, D. S., & Iosifescu, D. V. (2013). Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression. Biological Psychiatry, 74(4), 250-256. https://doi.org/10.1016/j.biopsych.2012.06.022
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