Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression

Biological Psychiatry. 2012​.

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, and Dan V. Iosifescu

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.

Major depressive disorder (MDD) is associated with a very high degree of morbidity and public health cost, in part due to the limited effectiveness of current antidepressant treatments…

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