SUMMARY  

• TRANSFORM-2 was a phase III, double-blind, multicenter, active-controlled study to evaluate the efficacy and safety of switching patients with treatment-resistant depression (TRD) from an ineffective antidepressant (AD) to flexibly dosed SPRAVATO plus a newly initiated AD or to a newly initiated AD (active comparator) plus placebo nasal spray.¹
• The primary endpoint was change from baseline to day 28 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score.
  • 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.² 
• Data from the trial found that SPRAVATO-treated patients had a greater likelihood of achieving improvement on all symptoms of depression, as measured by the individual MADRS items. Details of the change in individual items of the MADRS are reported below.² 

CLINICAL DATA

TRANSFORM 2

• A double-blind (DB), randomized, active-controlled phase III study, TRANSFORM-2,evaluated the efficacy and safety of SPRAVATO in addition to an AD for the reduction of depressive symptoms from baseline to day 28. This post-hoc analysis used MADRS data to evaluate symptom changes. The total scores change and proportions of individual item change scores on the MADRS were evaluated at days 15 and 28; analysis of variance was used to test differences on total scores.² 
• The minimally important difference of the MADRS total score is generally agreed to be 2 points.^2-4  The mean reduction in total scores on the MADRS, indicating improvement, was numerically greater at day 15 (−2.0; P=0.189) and statistically significantly greater at day 28 (−4.4; P=0.017) in the SPRAVATO plus AD arm compared with placebo plus AD (see Table: MADRS Total Score and Change From Baseline Score at Days 15 and 28).² 
• Proportions of those who improved (defined as ≥2 point reduction on a 7-point scale for the MADRS items) were numerically greater in the SPRAVATO plus AD group compared with the placebo plus AD group across all items at both day 15 and day 28 (see Table: MADRS Items From Baseline to Days 15/28 in SPRAVATO Plus AD Versus Placebo Plus).²