Ketamine for refractory depression: Save the best for last?

Ketamine has recently been shown to be non-inferior to electroconvulsive therapy (ECT), one of psychiatry's most effective treatments for depression. Given the novelty of ketamine as well as its interventional nature, ketamine is currently viewed as an alternative to ECT and as such, considered a third-line agent for treatment-refractory depression. However, available data suggest that ketamine carries a low side-effect burden and is better tolerated than many second-line augmentation strategies for depression. With this combination of higher efficacy and lower side-effect burden in conjunction with what is known about treatment outcomes in relation to the duration of untreated illness, it is in the best interest of patients for the field of psychiatry to evaluate ketamine as a second-line augmentation strategy for refractory depression.