A single infusion of ketamine reduces depressive symptoms more than an active placebo (midazolam) in people with treatment-resistant depression 24 hours after treatment. Repeated infusions produce cumulative antidepressant effects and double the response rate; 59% of participants responded after a median of three infusions. Weekly maintenance infusions sustain the reduction in depressive symptoms among responders but do not produce further improvement. The findings suggest that repeated ketamine infusions offer a viable strategy for prolonging antidepressant effects in this population.
A multi-centre trial across four Canadian institutions will compare intravenous ketamine infusions with electroconvulsive therapy (ECT) for treating major depressive episodes in 240 patients with major depressive or bipolar disorder. Patients are randomized to either ECT or ketamine three times per week for three to four weeks; non-responders cross over to the other treatment. Responders enter a six-month maintenance phase. The primary outcome is change in depression severity scores assessed by blinded raters. The study aims to identify clinical, molecular, and imaging predictors of response to each treatment.