SPN-820 Shows Rapid and Significant Improvement in Major Depressive Disorder Symptoms

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CONFERENCE REPORTER

A new phase 2, open-label clinical trial has demonstrated that SPN-820, a novel antidepressant, provides rapid and substantial improvement in adults with major depressive disorder (MDD).¹ Patients taking SPN-820 alongside their existing antidepressant medication showed significant symptom relief within hours of administration, with continued progress over the study period. SPN-820 is an oral formulation of NV-5138 with a novel mechanism of action. The new information was presented via poster session at the 30th Annual Nevada Psychiatric Association National Psychopharmacology Update.¹

Study Design and Patient Response

This 10-day phase 2 study evaluated SPN-820 as an adjunct treatment for MDD in patients who had not achieved full symptom relief from conventional antidepressants. The trial included 40 participants aged 18 to 65 with moderate to severe MDD symptoms.

Patients received 2400 mg of SPN-820 every 3 days, administered orally. The study’s primary efficacy measures were the HAM-D6 and MADRS score changes, while safety outcomes included adverse events, vital sign monitoring, and assessments for dissociative symptoms, hallucinations, and suicidality.

By day 10, more than half of the participants achieved symptom remission, a result that suggests SPN-820 could be an effective alternative for patients who do not fully respond to traditional antidepressants.

Rapid Reduction in Depression Symptoms

Preclinical research shows SPN-820 increases neuroplasticity by acting intracellularly to enhance activity of Mechanistic Target of Rapamycin Complex 1.¹ The study results show that SPN-820 produced meaningful symptom relief within just 4 hours of the first dose. Patients experienced an average 50% reduction in Montgomery–Åsberg Depression Rating Scale (MADRS) scores. By day 10, 84.2% of participants met the MADRS response criteria, and 63.2% achieved remission, demonstrating the potential long-term benefits of this novel treatment.¹

Additionally, the Hamilton Depression Rating Scale (HAM-D6) scores showed significant improvement early in treatment, reinforcing SPN-820’s rapid-acting antidepressant properties.

Safety and Tolerability Profile

SPN-820 was well tolerated, with no serious adverse events reported. Only 1 patient discontinued treatment due to worsening hypertension, which was deemed unrelated to the study drug.

Common mild-to-moderate adverse events included headache, nausea, somnolence, dizziness, and fatigue, occurring in a minority of participants. Notably, there were no reports of dissociative effects, hallucinations, or psychosis, side effects commonly associated with other rapid-acting antidepressants such as ketamine-derived treatments.

Suicidal ideation among participants also decreased significantly during the trial, further highlighting the potential mental health benefits of SPN-820.

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Reference

1. Ceresoli-Borroni G, Targum SD, Alleyne N, et al. Efficacy and safety of SPN-820 for adults with major depressive disorder: Primary results from a phase 2, open-label trial. Presented at: Nevada Psychiatric Association 30^th Annual Psychopharmacology Update; February 13, 2025.