Original Research J Clin Psychiatry August 2025

Rapid Onset and Sustained Efficacy of Onfasprodil (MIJ821), a Novel NR2B Negative Allosteric Modulator, in Patients With Treatment-Resistant Depression: A Phase 2, Randomized, Placebo-Controlled, Proof-of-Concept Study

Full Article Read the complete peer-reviewed article in J Clin Psychiatry. Clinical Summary Patients with treatment-resistant depression need options that work within hours, not weeks, but currently available rapid-acting NMDA-modulating treatments carry dissociative and psychotomimetic risks. This study tests whether onfasprodil, an NR2B-selective NMDA negative allosteric modulator, can deliver rapid antidepressant effects with a more manageable tolerability profile. FAQ What is onfasprodil, and why is it being studied for treatment-resistant depression? 10 questions
Key Takeaways At 24 hours after the first infusion, pooled onfasprodil 0.16 mg/kg showed a larger placebo-adjusted MADRS benefit than pooled onfasprodil 0.32 mg/kg (−8.25 vs −5.71), suggesting that increasing dose did not improve early antidepressant signal in this study. 6 takeaways Clinical Guide How do clinicians identify adults with major depressive disorder who match the treatment-resistant depression population studied for intravenous onfasprodil? 4 steps Clinical Guide How should clinicians monitor early antidepressant response and infusion-related adverse effects after intravenous onfasprodil in treatment-resistant depression? 7 steps
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