Intranasal esketamine in treatment-resistant depression: a profile of its use

Enhanced material for this Adis Drug Q&A can be found here

Abstract

Intranasal esketamine (Spravato™), the S-enantiomer of ketamine, targets the glutamatergic system via non-competitive antagonism of the N-methyl-D-aspartate receptor, thereby providing a novel approach to traditional antidepressants that target modulation of the monoaminergic system. In conjunction with an oral antidepressant (OAD), intranasal esketamine is approved in the USA for use in adult patients with treatment-resistant depression (TRD). Given its novel mechanism and rapid onset of action, convenient weekly or once every 2 weeks maintenance regimen, and the current paucity of approved pharmacotherapy options for TRD, esketamine nasal spray in conjunction with an OAD provides an important treatment option for this difficult-to-treat high-risk patient population. In pivotal clinical trials in adult patients with TRD, flexible-dose intranasal esketamine in conjunction with a newly initiated OAD provided rapid and sustained improvements in depression symptoms, and had a manageable tolerability and safety profile. Further long-term clinical experience is required to fully define the potential benefits and risks of esketamine therapy in combination with an OAD in TRD.