Esketamine Monotherapy in Adults With Treatment-Resistant Depression: A Randomized Clinical Trial

Area of Science:

• Psychiatry and Neuroscience
• Pharmacology
• Clinical Trials

Background:

• Esketamine nasal spray is approved for treatment-resistant depression (TRD) when used with oral antidepressants.
• The efficacy of esketamine nasal spray as monotherapy for TRD has not been previously evaluated.

Purpose of the Study:

• To assess the efficacy and safety of esketamine monotherapy compared to placebo in reducing depressive symptoms in patients with TRD.
• To evaluate esketamine monotherapy's effectiveness in treatment-resistant depression.

Main Methods:

• Phase 4, double-blind, placebo-controlled randomized clinical trial involving 378 adults with major depressive disorder and inadequate response to oral antidepressants.
• Participants received fixed-dose intranasal esketamine (56 mg or 84 mg) or placebo twice weekly for 4 weeks after an antidepressant-free period.
• The primary efficacy endpoint was the change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 28.

Main Results:

• Esketamine monotherapy demonstrated statistically significant reductions in MADRS scores at day 28 compared to placebo for both 56 mg (-5.1 points) and 84 mg (-6.8 points) doses.
• Significant improvements were also observed at 24 hours post-first dose for both esketamine doses.
• Common treatment-emergent adverse events included nausea, dissociation, dizziness, and headache.

Conclusions:

• Esketamine monotherapy is effective in reducing depressive symptoms in adult patients with TRD.
• This finding suggests esketamine monotherapy could offer a new treatment option for TRD patients experiencing tolerability issues or nonresponse to oral antidepressants.