Esketamine versus placebo on time to remission in major depressive disorder with acute suicidality.
BMC Psychiatry August 11, 2023 DOI: 10.1186/s12888-023-05017-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Post hoc analysis of pooled data from two phase 3 randomized controlled trials Double-blind Peer reviewed |
|---|---|
| Sample size | 451 |
| Population | Adults with major depressive disorder with acute suicidal ideation or behavior |
| Intervention | standard of care |
| Duration | Double-blind treatment phase with a follow-up phase |
| Measures | Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impression-Severity of Suicidality-revised version (CGI-SS-r) |
| Topics | Depression Esketamine |
| Registration | NCT03039192 NCT03097133 |
| Key findings | Esketamine plus standard of care produced significantly shorter median times to remission (15 versus 23 days) and consistent remission (23 versus 50 days) than placebo plus standard of care, with more patients in remission by Day 25 (65.2% versus 55.5%) and a greater median percentage of days in remission (27.1% versus 8.3%). The authors conclude these findings underscore the clinical benefits of esketamine for adults with MDD with suicidality. |
Abstract
Abstract:
Background: Esketamine (ESK) nasal spray, taken with oral antidepressant therapy, is approved for the treatment of depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior. In pooled analyses of two pivotal phase 3 studies, ASPIRE I and II, remission rates were consistently higher among patients with MDD with active suicidality who were treated with ESK + standard of care (SOC) versus placebo (PBO) + SOC at all time points in the double-blind and most time points in the follow-up phases. The current analysis of the ASPIRE data sets assessed the effect of ESK + SOC versus PBO + SOC on additional remission-related endpoints: time to achieving remission and consistent remission, proportion of patients in remission and consistent remission, and days in remission.
Methods: Post hoc analysis of pooled data from ASPIRE I and II (N = 451). Remission and consistent remission were defined as Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤ 12 at any given visit or two consecutive visits, respectively. Combined endpoints utilizing Clinical Global Impression-Severity of Suicidality-revised version [CGI-SS-r] ≤ 1 (i.e., not suicidal/questionably suicidal) along with the remission and consistent remission definitions (i.e., MADRS total score ≤ 12) were also examined.
Results: The median times to remission and consistent remission of MDD were significantly shorter in ESK + SOC versus PBO + SOC (15 versus 23 [p = 0.005] and 23 versus 50 days [p = 0.007], respectively) and a greater proportion of patients in ESK + SOC achieved remission and consistent remission by Day 25 (65.2% versus 55.5% and 54.2% versus 39.8%, respectively). Similar results were obtained using the combined endpoint for both remission definitions. The median percent of days in remission during the double-blind treatment phase was significantly greater in ESK + SOC (27.1% or 5 days) versus PBO + SOC (8.3% or 2 days; p = 0.006), and the significant difference was maintained during follow-up.
Conclusion: Treatment with ESK + SOC versus PBO + SOC resulted in significantly shorter time to remission, greater proportion of patients in remission, and greater percent of days in remission using increasingly rigorous definitions of remission. These findings underscore the clinical benefits of ESK for adults with MDD with suicidality.
Trial Registration: ClinicalTrials.gov registry NCT03039192 (registered February 1, 2017) and NCT03097133 (registered March 31, 2017).
Comparable studies
Other randomized controlled trials on esketamine for depression, most cited first.