TY - JOUR
T1 - REL-1017 (Esmethadone) as Adjunctive Treatment in Patients With Major Depressive Disorder
T2 - A Phase 2a Randomized Double-Blind Trial
AU - Maurizio, Fava
AU - Stahl, Stephen
AU - Pani, Luca
AU - Martin, Sara De
AU - Pappagallo, Marco
AU - Guidetti, Clotilde
AU - Alimonti, Andrea
AU - Bettini, Ezio
AU - Mangano, Richard M.
AU - Wessel, Thomas
AU - Somer, Marc
AU - Caron, Judy
AU - Vitolo, Ottavio V.
AU - DiGuglielmo, Gina R.
AU - Gilbert, Adam
AU - Mehta, Hiren
AU - Kearney, Morgan
AU - Mattarei, Andrea
AU - Gentilucci, Marco
AU - Folli, Franco
AU - Traversa, Sergio
AU - Inturrisi, Charles E.
AU - Manfredi, Paolo L.
N1 - Publisher Copyright:
© 2022 American Psychiatric Association. All rights reserved.
PY - 2022/2
Y1 - 2022/2
N2 - Objective: The purpose of this study was to examine the efficacy endpoint was the Montgomery-Åsberg Depreseffects of REL-1017 (esmethadone), a novel N-methyl-Dsion Scale (MADRS) score. All 62 randomly assigned aspartate receptor (NMDAR) channel blocker, in patients patients were included in the full analysis set population with major depressive disorder who failed to benefit from analysis. one to three standard antidepressant treatments in their Results: Patients experienced mild or moderate transient current major depressive episode. adverse events and no evidence of dissociative or psyMethods: A 7-day phase 2 multicenter randomized chotomimetic effects, opioid effects, or withdrawal signs double-blind placebo-controlled trial, comprising three and symptoms. The improvement in MADRS score shown arms, was conducted to assess the safety, tolerability, on day 4 in both of the REL-1017 dosage groups was suspharmacokinetics, and efficacy of two dosages of RELtained through day 7 (last dose) and day 14 (7 days after 1017 (25 mg or 50 mg orally once a day). Patients were the last dose), with effect sizes from 0.7 to 1.0. randomly assigned in a 1:1:1 ratio to placebo (N522), Conclusions: This trial showed favorable safety, tolerabilREL-1017 25 mg/day (N519), or REL-1017 50 mg/day ity, and pharmacokinetic profiles and suggests that REL(N521). Safety scales included the 4-item Positive Symp-1017 may have rapid and sustained antidepressant effects tom Rating Scale for psychotomimetic symptoms, the compared with placebo in patients with inadequate Clinician-Administered Dissociative States Scale for dis-responses to antidepressant treatments. These results will sociative symptoms, the Clinical Opiate Withdrawal Scale need confirmation in larger and longer trials. for withdrawal signs and symptoms, and the Columbia-Suicide Severity Rating Scale for suicidality. The primary Am J Psychiatry 2022; 179:122–131; doi: 10.1176/appi.ajp.2021.21020197
AB - Objective: The purpose of this study was to examine the efficacy endpoint was the Montgomery-Åsberg Depreseffects of REL-1017 (esmethadone), a novel N-methyl-Dsion Scale (MADRS) score. All 62 randomly assigned aspartate receptor (NMDAR) channel blocker, in patients patients were included in the full analysis set population with major depressive disorder who failed to benefit from analysis. one to three standard antidepressant treatments in their Results: Patients experienced mild or moderate transient current major depressive episode. adverse events and no evidence of dissociative or psyMethods: A 7-day phase 2 multicenter randomized chotomimetic effects, opioid effects, or withdrawal signs double-blind placebo-controlled trial, comprising three and symptoms. The improvement in MADRS score shown arms, was conducted to assess the safety, tolerability, on day 4 in both of the REL-1017 dosage groups was suspharmacokinetics, and efficacy of two dosages of RELtained through day 7 (last dose) and day 14 (7 days after 1017 (25 mg or 50 mg orally once a day). Patients were the last dose), with effect sizes from 0.7 to 1.0. randomly assigned in a 1:1:1 ratio to placebo (N522), Conclusions: This trial showed favorable safety, tolerabilREL-1017 25 mg/day (N519), or REL-1017 50 mg/day ity, and pharmacokinetic profiles and suggests that REL(N521). Safety scales included the 4-item Positive Symp-1017 may have rapid and sustained antidepressant effects tom Rating Scale for psychotomimetic symptoms, the compared with placebo in patients with inadequate Clinician-Administered Dissociative States Scale for dis-responses to antidepressant treatments. These results will sociative symptoms, the Clinical Opiate Withdrawal Scale need confirmation in larger and longer trials. for withdrawal signs and symptoms, and the Columbia-Suicide Severity Rating Scale for suicidality. The primary Am J Psychiatry 2022; 179:122–131; doi: 10.1176/appi.ajp.2021.21020197
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U2 - 10.1176/APPI.AJP.2021.21020197
DO - 10.1176/APPI.AJP.2021.21020197
M3 - Article
C2 - 34933568
AN - SCOPUS:85123969646
SN - 0002-953X
VL - 179
SP - 122
EP - 131
JO - American Journal of Psychiatry
JF - American Journal of Psychiatry
IS - 2
ER -
