SUMMARY  

• ASPIRE-I and ASPIRE-II are two double-blind, randomized, placebo-controlled studies that evaluated the efficacy and safety of SPRAVATO in addition to comprehensive standard of care (SOC) for the rapid reduction of depressive symptoms in those who had moderate to severe major depressive disorder (MDD) and active suicidal ideation with intent.^1,2
• The primary endpoint was change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at 24 hours after the first dose.
  • The 10 items of the MADRS included the following symptoms: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts.³
• Pooled data from both trials demonstrated that SPRAVATO-treated patients had a greater likelihood of achieving clinically meaningful improvement on all symptoms of depression, as measured by the individual MADRS items.⁴ Details of the change in individual items of the MADRS are reported below.

CLINICAL DATA

ASPIRE-I & ASPIRE-II

• Two-double-blind (DB), randomized, placebo (PBO)-controlled studies, ASPIRE-I^1, and ASPIRE-II²,evaluated the efficacy and safety of SPRAVATO in addition to comprehensive SOC for the reduction of depressive symptoms 24 hours after the first SPRAVATO dose in those who have major depressive disorder (MDD) and active suicidal ideation with intent.
• A clinically meaningful within-group change from baseline on the MADRS has been reported to range between a 6- to 9-point reduction in total score.^5,6
  • A 6-point change from baseline on the MADRS has been shown to correspond to a clinically meaningful change (defined as a 1-point change) on the clinician’s rating of overall depression severity (Clinical Global Impression – Severity [CGI-S]).⁷
• When treatment groups (SPRAVATO 84 mg + SOC, N=224; PBO + SOC, N=225) are compared to each other, a 2-point difference in MADRS between groups has been found to be clinically meaningful.^8,9
  • The least squares (LS) mean change in MADRS total score from baseline to 24 hours post first dose (Day 2) was:
    • SPRAVATO 84 mg + SOC: -16.1; PBO + SOC: -12.6⁴
  • The least squares mean difference (LSMD) in MADRS total score from baseline to 24 hours post first dose (Day 2) was:
    • -3.8 (95% confidence interval [CI]: -5.75 to -1.89)⁴
• In terms of individual items of the MADRS, early benefit with SPRAVATO was greatest (i.e., lower limit of 95% CI>1.0):⁴
  • at 4 hours after the first dose on reported sadness (odds ratio [OR]: 2.29; 95% CI: 1.5 to 3.5), apparent sadness (OR: 1.99; 95% CI: 1.31 to 3.02), inner tension (OR: 1.92; 95% CI: 1.23 to 3.00), suicidal thoughts (OR: 1.91; 95% CI:  1.30 to 2.82), inability to feel (OR: 1.75; 95% CI: 1.11 to 2.75), and pessimistic thoughts (OR:1.63; 95% CI: 1.03 to 2.57). Other measures (with lower limit of 95% CI≤1.0) included: reduced appetite (OR: 1.19; 95% CI: 0.68 to 2.08), concentration difficulties (OR: 1.39; 95% CI: 0.88 to 2.20), and lassitude (OR: 1.54; 95% CI: 0.99 to 2.39).⁴
  • at 24 hours on concentration difficulties (OR: 2.47; 95% CI: 1.57 to 3.89), apparent sadness (OR: 2.13; 95% CI: 1.41 to 3.24), inner tension (OR: 2.13; 95% CI: 1.36 to 3.34), inability to feel (OR: 1.95; 95% CI: 1.28 to 2.99), reported sadness (OR: 1.77; 95% CI: 1.18 to 2.66), reduced sleep (OR: 1.67; 95% CI: 1.05 to 2.67), and pessimistic thoughts (OR: 1.62; 95% CI: 1.05 to 2.50). Other measures (with lower limit of 95% CI≤1.0) included: reduced appetite (OR: 1.15; 95% CI: 0.69 to 1.93), lassitude (OR: 1.55; 95% CI: 1.00 to 2.40), and suicidal thoughts (OR: 1.28; 95% CI: 0.87 to 1.87).⁴
  • MADRS items were rated on a scale of 0 to 6 where 0 indicates no abnormality and 6 indicates severe. The reduced sleep item was not assessed at the 4-hour post-first dose time point.⁴

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 17 January 2025.