A randomized placebo-controlled trial tested whether a fixed low dose of oral esketamine (30 mg three times daily) could reduce depression severity in patients with treatment-resistant depression. Over six weeks, the drug showed no benefit compared to placebo on the Hamilton Depression Rating Scale. Dizziness and sleep hallucinations were more common with esketamine. In an open-label extension phase where doses were individually titrated up to 3.0 mg/kg twice weekly, depressive symptoms decreased substantially. The findings suggest that fixed low-dose oral esketamine is ineffective, but individually adjusted higher doses may hold promise for treatment-resistant depression.
A triple-blind randomized placebo-controlled trial investigates daily oral esketamine versus placebo as an add-on to regular antidepressants in patients with treatment-resistant depression over 6 weeks, followed by a 4-week follow-up. This is the first such trial to examine the efficacy, safety, tolerability, mechanisms of action, and economic impact of repeated oral esketamine administration. If effective and tolerated, oral esketamine offers practical advantages over intravenous administration. The study aims to address the urgent need for additional treatment strategies for treatment-resistant depression.