Summary

• The phase 3 program in patients with treatment-resistant depression (TRD) and major depressive disorder (MDD) with active suicidal ideation with intent studied SPRAVATO in combination with oral antidepressants.
• In clinical trials in TRD, SPRAVATO was co-administered with one of the following newly initiated oral antidepressants (AD): duloxetine, escitalopram, sertraline, or venlafaxine XR.^1-5 In clinical trials in MDD with active suicidal ideation with intent, SPRAVATO was co-administered with newly initiated or optimized AD therapy.^6,7
• During the phase 3 program in TRD, the primary rationale for the simultaneous initiation of oral AD in conjunction with SPRAVATO was to help sustain long-term efficacy.
  • Specifically, the long-term maintenance of effects study (SUSTAIN-1) was designed to determine if subjects with stable response/remission to an initial 16 weeks of SPRAVATO + oral AD therapy could sustain longer-term maintenance with oral AD alone after SPRAVATO was discontinued and this was a key reason for initiating a new oral AD in the induction phase of short-term flexible and fixed-dose studies (TRANSFORM-1 and -2).⁸
• In the phase 3 program in TRD, SPRAVATO was studied in patients who have had nonresponse (i.e., ≤25% improvement since initiation) to 2 or more ADs of adequate dose and duration in the current depressive episode. As such, a new oral AD was initiated instead of one to which the patient had previously not responded, as it was thought to provide subjects a greater likelihood of achieving sustained improvement after SPRAVATO was discontinued.^1-5
• In the ASPIRE studies, patients presented to an emergency department with a psychiatric emergency, MDD with active suicidal ideation with intent, that required immediate intervention.^6,7 Current standard practice includes initiation or optimization of oral antidepressants and, frequently, hospitalization.^9,10 Therefore, to be consistent with usual practice, patients in the ASPIRE trials had antidepressant therapy started, optimized, or augmented with few restrictions on the actual medications used.^6,7

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 05 January 2025.