Esketamine versus placebo on time to remission in major depressive disorder with acute suicidality.

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).

Treatment patterns and decision drivers to discharge patients with depression hospitalised for acute suicidal ideation in Europe.

BACKGROUND: There is limited published information about the management of patients with major depressive disorder (MDD) hospitalised for acute suicidal ideation (SI). This study aimed to identify treatment patterns and unmet needs in the management of these patients and the decision drivers for hospital discharge. METHODS: Cross-sectional survey-based study enrolling hospital-based European psychiatrists. The study had a qualitative and a quantitative stage, including a conjoint exercise. RESULTS: Each respondent (N = 413) managed, on average, 62 MDD patients with acute SI per typical three-month period; 76% of these patients required hospitalisation. Severity of SI and severity of MDD were considered the most important factors for hospital admission and discharge. In the conjoint analysis, these attributes accounted for 54% of the discharge decision. Key treatment goals included improving depressive symptoms and achieving MDD remission. Antidepressants were a standard treatment for 98% of respondents but 63% defined rapid onset of action as a critical unmet need, followed by a good tolerability profile (34%). LIMITATIONS: The study has a cross-sectional design representing respondents' behaviour and attitudes at a particular point in time. In the conjoint analysis, the results represent stated behaviour and not observed clinical behaviour. CONCLUSIONS: Physicians' decisions to admit and discharge patients with MDD hospitalised for acute SI are mostly driven by the severity of SI and depression. Antidepressants with rapid onset of action, which can quickly improve depressive symptoms, represent a key unmet need for these patients and may contribute to a higher likelihood of early discharge.

Patient profiles, initial hospital encounter characteristics, and hospital re-encounters of patients with a hospital emergency department visit or inpatient admission for major depressive disorder.

OBJECTIVES: To gain a better understanding of the characteristics of patients with a hospital encounter for major depressive disorder (MDD) and evaluate associated hospital resource utilization, hospital charges and costs, and hospital re-encounters. METHODS: Adult patients with a hospital encounter (i.e. emergency department [ED] visit only or inpatient admission) with MDD as the primary discharge diagnosis (index event) during July 2018‒March 2019 were selected from the Premier Healthcare Database. Patient characteristics, hospital resource utilization, and hospital charges and costs were evaluated during index events. During a 12-month follow-up, hospital re-encounters (MDD-related and all-cause ED visit only or inpatient readmissions) were examined. RESULTS: The study population included 77,178 patients with an index hospital encounter (ED visit only: 49.9%; inpatient admission: 50.1%) for MDD. The most common secondary mental health-related diagnosis was suicidal ideation/behavior, which was recorded in 51.8% of patients. The mean age was 38.2 years, 53.0% were female, and 72.1% were Caucasian. Among patients with an ED visit only, the mean index hospital charges and costs were $3,608 and $639, respectively. Among those with inpatient admissions, the mean length of stay was 4.9 days, and the mean index hospital charges and costs were $17,107 and $6,095, respectively. During the 12-month follow-up, 13.3% of patients in the overall study population had an MDD-related hospital re-encounter (primary or secondary discharge diagnosis code indicating MDD); nearly one-third (31.3%) occurred within 30 days post-discharge. During the follow-up, 28.1% had an all-cause hospital re-encounter with 29.7% having occurred within 30 days post-discharge. LIMITATIONS: Due to constraints of the Premier Healthcare Database, healthcare resource utilization and costs outside of the hospital could not be evaluated. CONCLUSIONS: Patients with a hospital encounter for MDD are relatively young, commonly have suicidal ideation/behavior, utilize substantial hospital resources, and have a high risk for a hospital re-encounter in the 30 days post-discharge.