Cognitive behavioral therapy (CBT) may help sustain the antidepressant effects of ketamine in people with treatment-resistant depression. In a trial, 42 patients with treatment-resistant depression received six intravenous ketamine infusions over three weeks. The 28 who responded were then randomized to CBT or treatment as usual for 14 weeks. On one depression scale, the CBT group showed significantly greater sustained improvement, with a moderate-to-large effect size. A smaller subset of ketamine responders also improved in emotional cognitive accuracy, while nonresponders did not. The findings are preliminary and need confirmation in larger trials.
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.
Adding cognitive behavioral therapy to esketamine treatment reduces suicidal ideation more than esketamine alone in people with major depression and suicidal thoughts. In a randomized trial of 93 patients, 72% completed the study, meeting feasibility goals. Those who received 16 weeks of CBT plus esketamine showed greater improvement on three measures of suicidal ideation than those receiving esketamine with usual care: a mean difference of -1.91 on the Beck Scale for Suicidal Ideation, -0.33 on the Clinician Global Improvement Scale for Suicide Severity, and -3.77 on the depression rating scale. No difference was found on the Columbia-Suicide Severity Rating Scale or in suicide-related events.