SUMMARY

• There are no clinical trials comparing SPRAVATO and Auvelity in patients with depression. The two medications are indicated for different patient populations.
• SPRAVATO is a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist indicated for the treatment of¹:
  • Treatment-resistant depression (TRD) in adults, as monotherapy or in conjunction with an oral antidepressant.
  • Depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior in conjunction with an oral antidepressant.
• Auvelity is a combination of dextromethorphan, an uncompetitive NDMA receptor antagonist and sigma-1 receptor agonist, and bupropion, an aminoketone and CYP450 2D6 inhibitor, indicated for the treatment of MDD in adults.²
  • Auvelity was evaluated in a phase 3 study in TRD. However, the clinical trial did not achieve its primary outcome.³ 
• According to an in vitro study using a porcine model, the binding affinity (Ki) of esketamine to the phencyclidine (PCP) binding site on the NMDA receptor was 440±100 nM and the Ki of dextromethorphan was 3400±800 nM.⁴ Therefore, esketamine had ~8-fold greater affinity compared to dextromethorphan.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENTDrug databases (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 20 May 2025.