Ketamine provides rapid but short-lived antidepressant effects. In an open-label trial, patients with treatment-resistant depression received a 2-week course of intravenous ketamine alongside a 10-week course of cognitive behavioral therapy (CBT). Of 16 participants, 8 responded to ketamine and 7 achieved remission in the first 2 weeks. Among responders, 25% relapsed by the end of CBT, and the median time to relapse was 12 weeks after ketamine. Among remitters, 2 of 7 maintained remission through 8 weeks after ketamine. Ketamine nonresponders did not benefit from CBT. The combination may help sustain ketamine's effects, but randomized controlled trials are needed.
The EQUIVALENCE trial protocol describes a non-inferiority, comparative effectiveness study designed to test whether intranasal esketamine is no less effective than intravenous ketamine for treating treatment-resistant depression. The study will compare the two treatments head-to-head in patients who have not responded to prior antidepressant therapies. The protocol outlines the trial's design, including randomization, dosing regimens, outcome measures, and statistical analysis plan. By directly comparing these two forms of ketamine, the trial aims to provide evidence on whether the more convenient intranasal route can match the efficacy of the intravenous formulation, potentially offering a more accessible treatment option.