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.
Meredith Castro, Samuel T Wilkinson, Rayan K Al Jurdi, Mary Pat Petrillo, Naim Zaki, Stephane Borentain, Dong Jing Fu, Ibrahim Turkoz, Liping Sun, Brianne Brown, Patricia Cabrera
CNS Drugs August 9, 2023 DOI: 10.1007/s40263-023-01026-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Interim subgroup analysis of a long-term clinical trial Peer reviewed |
|---|---|
| Sample size | 96 |
| Population | Adults aged 18-64 years with treatment-resistant depression who achieved stable remission or response with esketamine plus oral antidepressant in SUSTAIN-1, relapsed, and entered the induction phase of SUSTAIN-3 |
| Interventions | Esketamine nasal spray oral antidepressant |
| Duration | Second induction phase followed by optimization/maintenance phase; specific durations not stated |
| Measures | Montgomery-Åsberg Depression Rating Scale (MADRS), Patient Health Questionnaire 9-item (PHQ-9), treatment-emergent and serious adverse events |
| Topics | Ketamine Depression Esketamine |
| Keywords | Humans Antidepressive agents Treatment outcome Adolescent Middle aged Young adult Nasal sprays Depressive disorder, treatment-resistant |
| Registration | NCT02493868 NCT02782104 |
| Key findings | A second induction course of esketamine nasal spray plus an oral antidepressant produced substantial improvements in depressive symptoms that were maintained during optimization/maintenance, with MADRS response rates of 71.9% and 73.4% in the two prior-treatment groups and remission rates of 62.5% and 60.9%. No new safety signals were identified. |
Abstract
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.
Comparable studies
Other non-randomized and open-label trials on esketamine for depression, most cited first.