Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression

• Published in: Biological psychiatry (1969) 2013-08, Vol.74 (4), p.250-256
• Main Authors: Murrough, James W, Perez, Andrew M, Pillemer, Sarah, Stern, Jessica, Parides, Michael K, aan het Rot, Marije, Collins, Katherine A, Mathew, Sanjay J, Charney, Dennis S, Iosifescu, Dan V
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Antidepressant; Antidepressive Agents - administration & dosage; Antidepressive Agents - therapeutic use; Biological and medical sciences; Depression; Depressive Disorder, Treatment-Resistant - drug therapy; experimental therapeutics; Female; glutamate; Humans; Infusions, Intravenous; ketamine; Ketamine - administration & dosage; Ketamine - therapeutic use; major depressive disorder; Male; Medical sciences; Middle Aged; Mood disorders; Neuropharmacology; Pharmacology. Drug treatments; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; treatment-resistant depression
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2012.06.022

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.