What does this research mean for the field?

Satoprodil, an oral NMDA subunit GluN2B-selective negative allosteric modulator, is well tolerated but does not significantly reduce depressive symptoms compared to placebo when used as monotherapy or adjunctive therapy in patients with major depressive disorder. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To evaluate the safety, tolerability, and clinical efficacy of satoprodil, an oral GluN2B-selective negative allosteric modulator, as monotherapy and adjunctive therapy in patients with major depressive disorder.

September 7, 2026NeuropsychopharmacologyOpen Access

NMDA subunit 2B-selective negative allosteric modulator satoprodil (BI 1569912) as mono- and adjunctive therapy in patients with major depressive disorder: results from two phase 2 randomized, controlled trials

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Authors

ECElan A. Cohen GSGerard Sanacora KWKoichiro Watanabe

Discussion

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Overview

Randomized trial finds satoprodil fails to improve depressive symptoms beyond placebo in major depressive disorder, highlighting limited efficacy of GluN2B negative allosteric modulation.

Key Points

To evaluate the safety, tolerability, and clinical efficacy of satoprodil, an oral GluN2B-selective negative allosteric modulator, as monotherapy and adjunctive therapy in patients with major depressive disorder.
Two multicenter, randomized, placebo-controlled Phase 2 dose-finding trials evaluated once-daily satoprodil (5 mg, 10 mg, or 20 mg) versus placebo (2:1:1:2 ratio) over 6 weeks.
Participants aged 18–65 years with major depressive disorder were enrolled in an adjunctive therapy trial (N=243, alongside ongoing antidepressant treatment) or a monotherapy trial (N=225).
The primary endpoint for both trials was the change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6.
In the adjunctive trial (N=243), adjusted mean (SE) change in MADRS score at Week 6 was −12.0 (1.1) with placebo versus −7.8 (1.6) with 5 mg, −11.9 (1.6) with 10 mg, and −12.3 (1.2) with 20 mg satoprodil.
In the monotherapy trial (N=225), adjusted mean (SE) change in MADRS score at Week 6 was −10.3 (1.4) with placebo versus −13.6 (2.1) with 5 mg, −10.6 (2.0) with 10 mg, and −10.0 (1.4) with 20 mg satoprodil.
Satoprodil was well tolerated across all doses over 6 weeks but did not reduce depressive symptoms beyond placebo in a clinically relevant manner in either trial.

Cite This Study

Cohen et al. (2026) studied this question.

synapsesocial.com/papers/6a9e85c4c3034f961570e1d1 https://doi.org/10.1038/s41386-026-02538-4

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September 7, 2026NeuropsychopharmacologyOpen Access

NMDA subunit 2B-selective negative allosteric modulator satoprodil (BI 1569912) as mono- and adjunctive therapy in patients with major depressive disorder: results from two phase 2 randomized, controlled trials

View Full Paper

Ask AI

Bookmark

Authors

ECElan A. Cohen GSGerard Sanacora KWKoichiro Watanabe

Discussion

Member takes

Overview

Randomized trial finds satoprodil fails to improve depressive symptoms beyond placebo in major depressive disorder, highlighting limited efficacy of GluN2B negative allosteric modulation.

Key Points

To evaluate the safety, tolerability, and clinical efficacy of satoprodil, an oral GluN2B-selective negative allosteric modulator, as monotherapy and adjunctive therapy in patients with major depressive disorder.
Two multicenter, randomized, placebo-controlled Phase 2 dose-finding trials evaluated once-daily satoprodil (5 mg, 10 mg, or 20 mg) versus placebo (2:1:1:2 ratio) over 6 weeks.
Participants aged 18–65 years with major depressive disorder were enrolled in an adjunctive therapy trial (N=243, alongside ongoing antidepressant treatment) or a monotherapy trial (N=225).
The primary endpoint for both trials was the change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6.
In the adjunctive trial (N=243), adjusted mean (SE) change in MADRS score at Week 6 was −12.0 (1.1) with placebo versus −7.8 (1.6) with 5 mg, −11.9 (1.6) with 10 mg, and −12.3 (1.2) with 20 mg satoprodil.
In the monotherapy trial (N=225), adjusted mean (SE) change in MADRS score at Week 6 was −10.3 (1.4) with placebo versus −13.6 (2.1) with 5 mg, −10.6 (2.0) with 10 mg, and −10.0 (1.4) with 20 mg satoprodil.
Satoprodil was well tolerated across all doses over 6 weeks but did not reduce depressive symptoms beyond placebo in a clinically relevant manner in either trial.

Cite This Study

Cohen et al. (2026) studied this question.

synapsesocial.com/papers/6a9e85c4c3034f961570e1d1 https://doi.org/10.1038/s41386-026-02538-4

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