Paolo L. Manfredi, MD

Original Research

Esmethadone (REL-1017) in Patients with Major Depressive Disorder and Antidepressant Tachyphylaxis

October 6, 2025

Esmethadone may be a potentially safe and effective adjunctive treatment for patients with MDD and antidepressant tachyphylaxis.

Letter to the Editor

Reasons for Maintaining the Classification of Esmethadone as an Investigational Uncompetitive NMDAR Antagonist Rapid Antidepressant: Reply to Ferré and Michaelides

September 8, 2025

The authors reply to Ferré and Michaelides’ letter commenting on their recent study of long-term esmethadone treatment in MDD.

Original Research

Long-Term Safety and Efficacy of Esmethadone in MDD

February 17, 2025

A durable improvement in MDD symptoms for up to 1 year was observed with esmethadone with high rates of response and remission.

Original Research

Esmethadone in Patients With Major Depressive Disorder and Inadequate Response to Standard Antidepressants

June 17, 2024

Although this trial of esmethadone did not meet its primary outcome, some secondary and post hoc outcomes were promising.

Original Research

REL-1017 Effects on Cognition in MDD

February 14, 2023

REL-1017 improved subjective measures of cognitive impairment, in addition to improving total MADRS and SDQ scores.