Effects of esketamine on patient-reported outcomes in major depressive disorder with active suicidal ideation and intent: a pooled analysis of two randomized phase 3 trials (ASPIRE I and ASPIRE II)
Pooled data from ASPIRE I and II indicate that esketamine nasal spray plus standard of care produced greater patient‑reported improvements in health‑related quality of life and treatment satisfaction than placebo plus standard of care in adults with major depressive disorder and active suicidal ideation. The benefit was statistically significant on the QLDS (LS mean difference −3.1, 95% CI −5.21 to −1.02), with non‑significant change on the Beck Hopelessness Scale and favourable trends on EQ‑5D‑5L indices and TSQM‑9 domains.
Authors
- Daniel Fu
- Daniel Ionescu
- Robert Lane
Published
Abstract
Purpose
To assess the effect of esketamine nasal spray on patient-reported outcomes (PROs) in patients with major depressive disorder having active suicidal ideation with intent (MDSI).
Methods
Patient-level data from two phase 3 studies (ASPIRE I; ASPIRE II) of esketamine + standard of care (SOC) in patients (aged 18–64 years) with MDSI, were pooled. PROs were evaluated from baseline through end of the double-blind treatment phase (day 25). Outcome assessments included: Beck Hopelessness Scale (BHS), Quality of Life (QoL) in Depression Scale (QLDS), European QoL Group-5-Dimension-5-Level (EQ-5D-5L), and 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9). Changes in BHS and QLDS scores (baseline to day 25) were analyzed using a mixed-effects model for repeated measures (MMRM).
Results
Pooled data for esketamine + SOC (n = 226; mean age: 40.5 years, 59.3% females) and placebo + SOC (n = 225; mean age: 39.6 years, 62.2% females) were analyzed. Mean ± SD change from baseline to day 25, esketamine + SOC vs placebo + SOC (least-square mean difference [95% CI] based on MMRM): BHS total score, − 7.4 ± 6.7 vs − 6.8 ± 6.5 [− 1.0 (− 2.23, 0.21)]; QLDS score, − 14.4 ± 11.5 vs − 12.2 ± 10.8 [− 3.1 (− 5.21, − 1.02)]. Relative risk (95% CI) of reporting perceived problems (slight to extreme) in EQ-5D-5L dimensions (day 25) in esketamine + SOC vs placebo + SOC: mobility [0.78 (0.50, 1.20)], self-care [0.83 (0.55, 1.27)], usual activities [0.87 (0.72, 1.05)], pain/discomfort [0.85 (0.69, 1.04)], and anxiety/depression [0.90 (0.80, 1.00)]. Mean ± SD changes from baseline in esketamine + SOC vs placebo + SOC for health status index: 0.23 ± 0.21 vs 0.19 ± 0.22; and for EQ-Visual Analogue Scale: 24.0 ± 27.2 vs 19.3 ± 24.4. At day 25, mean ± SD in domains of TSQM-9 scores in esketamine + SOC vs placebo + SOC were: effectiveness, 67.2 ± 25.3 vs 56.2 ± 26.8; global satisfaction, 69.9 ± 25.2 vs 56.3 ± 27.8; and convenience, 74.0 ± 19.4 vs 75.4 ± 18.7.
Conclusion
These PRO data support the patient perspective of the effect associated with esketamine + SOC in improving health-related QoL in patients with MDSI. Trial registration: ClinicalTrials.gov Identifier: ASPIRE I, NCT03039192 (Registration date: February 1, 2017); ASPIRE II, NCT03097133 (Registration date: March 31, 2017).
Research Summary of 'Effects of esketamine on patient-reported outcomes in major depressive disorder with active suicidal ideation and intent: a pooled analysis of two randomized phase 3 trials (ASPIRE I and ASPIRE II)'
Introduction
The authors note that major depressive disorder (MDD) is a leading cause of disability worldwide and that a substantial subset of people with MDD experience suicidal ideation; this subgroup has been associated with poorer health-related quality of life (HRQoL), greater work and activity impairment, and elevated suicide risk. Standard of care (SOC) in acute suicidal risk usually comprises psychiatric hospitalisation and initiation or optimisation of oral antidepressant therapy, but oral antidepressants can take several weeks to show effect and suicide risk often remains high following discharge. Esketamine nasal spray plus comprehensive SOC has regulatory approval for depressive symptoms in patients with MDD who have active suicidal ideation with intent, based on two identically designed Phase III trials (ASPIRE I and ASPIRE II) that demonstrated rapid clinician-rated reductions in depressive symptoms and an expected safety profile in this high-risk population. To broaden understanding of treatment impact from the patient perspective, the authors conducted a pooled post hoc analysis of patient-reported outcomes (PROs) collected in ASPIRE I and ASPIRE II. The pooled analysis aimed to evaluate self-reported hopelessness, depression-specific quality of life, general HRQoL, and medication satisfaction over the 4-week double-blind treatment phase, comparing esketamine plus SOC with placebo plus SOC.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Authors
- APA Citation
Jamieson, C., Canuso, C. M., Ionescu, D. F., Lane, R., Qiu, X., Rozjabek, H., Molero, P., & Fu, D. (2023). Effects of esketamine on patient-reported outcomes in major depressive disorder with active suicidal ideation and intent: a pooled analysis of two randomized phase 3 trials (ASPIRE I and ASPIRE II). Quality of Life Research, 32(11), 3053-3061. https://doi.org/10.1007/s11136-023-03451-9
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References (3)
Papers cited by this study that are also in Blossom
Ionescu, D. F., Lane, R., Lim, P. et al. · Journal of Clinical Psychiatry (2020)
Ionescu, D. F., Qiu, X., Lane, R. et al. · International Journal of Neuropsychopharmacology (2020)
Canuso, C. M., Ionescu, D. F., Li, X. et al. · Journal of Clinical Psychopharmacology (2021)
Cited By (1)
Papers in Blossom that reference this study
Pepe, M., Bartolucci, G., Marcelli, I. et al. · Brain Sciences (2023)
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