SUMMARY  

• There are no studies evaluating the efficacy or safety of concurrent treatment with Auvelity and SPRAVATO. 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 of:
  • Treatment-resistant depression (TRD) in adults, as monotherapy or in conjunction with an oral antidepressant¹
  • Depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior in conjunction with an oral antidepressant¹
• 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
• Although the two products are NMDA receptor antagonists, the pharmacodynamic effect of coadministration is unknown. 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.³ Therefore, esketamine had ~8-fold greater affinity compared to dextromethorphan.
• There is a potential for exacerbation of high blood pressure since both products have warnings regarding increased blood pressure in the Prescribing Information and require monitoring prior to initiating, and during, treatment.^1,2 The high blood pressure is mainly attributed to the bupropion component in Auvelity.²
  • Other side effects, such as dizziness, nausea, and somnolence, are also reported as adverse reactions in the Prescribing Information for both products.
• Clinically significant drug interactions are not expected with esketamine and bupropion based on pharmacokinetic studies.¹
• There are no PK studies with dextromethorphan and esketamine.
  • Esketamine is primarily metabolized through CYP2B6 and CYP3A4.¹
  • Dextromethorphan does not cause induction of CYP1A2, CYP3A4, or CYP2B6 and does not inhibit transporters at therapeutically relevant concentrations.²
• Please contact the manufacturer of Auvelity for more information regarding the safety and drug-drug interactions for this product.

Literature Search

A literature search of Ovid MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENTDrug File databases (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 19 August 2024.