Journal Article

Efficacy and Safety of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression Who Completed a Second Induction Period: Analysis of the Ongoing SUSTAIN-3 Study

Wilkinson, Samuel T., Petrillo, Mary Pat, Borentain, Stephane, Al Jurdi, Rayan K., Fu, Dong Jing, Turkoz, Ibrahim, Zaki, Naim, Cabrera, Patricia, Sun, Liping, Castro, Meredith, Brown, Brianne

2023

Overview

Background Treatment-resistant depression (TRD) is a chronic illness requiring long-term treatment. Esketamine nasal spray (ESK) has been studied in several long-term trials of patients with TRD, including SUSTAIN-1 (NCT02493868) and SUSTAIN-3 (NCT02782104). This subgroup analysis of SUSTAIN-3 evaluated patients with TRD who received a second induction (IND) and maintenance treatment with ESK plus oral antidepressant (AD) after a relapse in SUSTAIN-1. Methods Patients aged 18–64 years who achieved stable remission or response with ESK and subsequently relapsed after randomization to continue ESK or switch to placebo nasal spray (PBO) in SUSTAIN-1 and entered the IND phase of SUSTAIN-3 were included in this interim analysis. Response (≥50% improvement in total score from baseline for Montgomery–Åsberg Depression Rating Scale [MADRS] and Patient Health Questionnaire 9-item [PHQ-9]), remission (MADRS score ≤12; PHQ-9 total score <5), changes in depression rating scores (measured as mean change from baseline), and safety were evaluated (incidence of treatment-emergent and serious adverse events [AE]). Results Of the 96 eligible patients who entered IND in SUSTAIN-3, 32 (33.3%) were taking ESK+AD at the time of relapse in SUSTAIN-1 and 64 (66.7%) were taking AD+PBO. Substantial improvements in depressive symptoms were observed over the second IND phase in both groups and were maintained over the optimization/maintenance (OP/M) phase. MADRS response rates following a second IND were 71.9% and 73.4% for previously relapsed (PR) ESK+AD and PR-AD+PBO, respectively; remission rates were 62.5% and 60.9%, respectively. During the IND and OP/M phases, 58.3% and 83.3% of patients experienced a treatment-emergent AE, respectively. No patients discontinued due to an AE during the second IND. Conclusions Patients with TRD benefitted from receiving a second IND and maintenance treatment with ESK and no new safety signals were identified.

• Publisher: Springer International Publishing,Springer Nature B.V
• Subject: Adolescent / Adult / Adults / Antidepressants / Antidepressive Agents - adverse effects / Chronic illnesses / Clinical trials / Clinical Trials as Topic / Depressive Disorder, Treatment-Resistant - drug therapy / Humans / Ketamine / Ketamine - adverse effects / Medicine / Medicine & Public Health / Mental depression / Middle Aged / Nasal Sprays / Neurology / Neurosciences / Optimization / Original / Original Research Article / Patients / Personality disorders / Pharmacotherapy / Psychiatry / Psychopharmacology / Psychosis / Questionnaires / Remission / Remission (Medicine) / Safety / Suicidal behavior / Treatment Outcome / Treatment resistance / Young Adult