Murrough, Perez, et al.  Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression”  Biological Psychiatry  2013 Aug 15; 74(4): 250–256.

 

Highlights:

  • In this article, there were 24 patients treated with six IV infusions of ketamine (.5mg/kg) over 12 days.
  • Participants with TRD (n=24) underwent a washout of antidepressant medication followed by a series of up to six intravenous (IV) infusions of ketamine (0.5 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.
  • The overall response rate was 71% as defined as a reduction in the MADRS scale by greater than 50%.  The median time to relapse after the last ketamine infusion was 18 days.  25% were symptom-free at 90 days, and 75% of patients had symptom-free days between 11-27 days.
  • Side effects were reported to be a mild significant increase in dissociative symptoms.  One patient had to discontinue therapy due to an increase in blood pressure that did not respond to medications (highest BP 180/115).

Results:

The overall response rate at the study end was 70.8%. There was a large mean decrease in Montgomery–Asberg Depression Rating Scale (MADRS) score at two hours following the first ketamine infusion (18.9±6.6, p<0.001), and this decrease was largely sustained for the duration of the infusion period. Response at the study end was strongly predicted by the response at four hours (94% sensitive, 71% specific). Among responders, the median time to relapse following 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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