Discussion
ideation, treatment-resistant depression, depressive, psychiatric, depressive symptoms, MDD, suicidality
REMISSION
In ASPIRE I and II, ESK demonstrated a rapid reduction of depressive symptoms in patients with MDD with active suicidal ideation and intent who were experiencing a psychiatric emergency [In practice, temporary hospitalization leaves patients with MDD and suicidality vulnerable in the near term while antidepressant treatment takes weeks to be effective [A large body of literature points to the importance of rapidly achieving remission in patients with MDD and suicidality [In addition to the humanistic benefits of achieving remission, there are economic benefits as well. In patients with treatment-resistant depression, healthcare resource utilization (HRU) is lower during remission than during a major depressive episode [A strength of our analysis is that multiple, increasingly stringent assessments of remission were used and that the results obtained were robust and consistent. The benefits of ESK + SOC over PBO + SOC were maintained during the follow-up phase, when ESK treatment had been discontinued.Limitations of this analysis include the post-hoc nature of the evaluation and the lack of adjustment for multiple comparisons. In addition, the suicidality endpoint (CGI-SS-r), while an important component of the remission assessment, did not show a statistically significant difference favoring ESK in the ASPIRE studies. Therefore, the results should be interpreted in line with the exploratory nature of the analysis. Finally, MADRS and CGI-SS-r assessments were performed intermittently, thus the remission analyses used values at each visit or two consecutive visits and days of remission in between two assessments were based on the calculation of last observation carried backward as described in the Methods.