Esketamine versus placebo on time to remission in major depressive disorder with acute suicidality
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,...
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | BMC Psychiatry |
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| Online Access: | https://doi.org/10.1186/s12888-023-05017-y |
| _version_ | 1797451854265712640 |
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| author | Dong-Jing Fu Qiaoyi Zhang Ling Shi Stephane Borentain Shien Guo Maju Mathews Joana Anjo Abigail I. Nash Marguerite O’Hara Carla M. Canuso |
| author_facet | Dong-Jing Fu Qiaoyi Zhang Ling Shi Stephane Borentain Shien Guo Maju Mathews Joana Anjo Abigail I. Nash Marguerite O’Hara Carla M. Canuso |
| author_sort | Dong-Jing Fu |
| collection | DOAJ |
| description | 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). |
| first_indexed | 2024-03-09T15:00:22Z |
| format | Article |
| id | doaj.art-d92b57827e9447c8beae3bbfa80e1b55 |
| institution | Directory Open Access Journal |
| issn | 1471-244X |
| language | English |
| last_indexed | 2024-03-09T15:00:22Z |
| publishDate | 2023-08-01 |
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| series | BMC Psychiatry |
| spelling | doaj.art-d92b57827e9447c8beae3bbfa80e1b552023-11-26T13:56:44ZengBMCBMC Psychiatry1471-244X2023-08-0123111010.1186/s12888-023-05017-yEsketamine versus placebo on time to remission in major depressive disorder with acute suicidalityDong-Jing Fu0Qiaoyi Zhang1Ling Shi2Stephane Borentain3Shien Guo4Maju Mathews5Joana Anjo6Abigail I. Nash7Marguerite O’Hara8Carla M. Canuso9Janssen Research & Development, LLCJanssen Global Services, LLCEvidera-PPDJanssen Global Services, LLCEvidera-PPDJanssen Global Services, LLCJanssen Cilag-FarmacêuticaJanssen Scientific Affairs, LLCJanssen Global Services, LLCJanssen Research & Development, LLCAbstract 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).https://doi.org/10.1186/s12888-023-05017-yEsketamine nasal sprayDepressive disorderSuicidal ideationRemissionAntidepressant agents |
| spellingShingle | Dong-Jing Fu Qiaoyi Zhang Ling Shi Stephane Borentain Shien Guo Maju Mathews Joana Anjo Abigail I. Nash Marguerite O’Hara Carla M. Canuso Esketamine versus placebo on time to remission in major depressive disorder with acute suicidality BMC Psychiatry Esketamine nasal spray Depressive disorder Suicidal ideation Remission Antidepressant agents |
| title | Esketamine versus placebo on time to remission in major depressive disorder with acute suicidality |
| title_full | Esketamine versus placebo on time to remission in major depressive disorder with acute suicidality |
| title_fullStr | Esketamine versus placebo on time to remission in major depressive disorder with acute suicidality |
| title_full_unstemmed | Esketamine versus placebo on time to remission in major depressive disorder with acute suicidality |
| title_short | Esketamine versus placebo on time to remission in major depressive disorder with acute suicidality |
| title_sort | esketamine versus placebo on time to remission in major depressive disorder with acute suicidality |
| topic | Esketamine nasal spray Depressive disorder Suicidal ideation Remission Antidepressant agents |
| url | https://doi.org/10.1186/s12888-023-05017-y |
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