Adjunctive dopaminergic enhancement of esketamine in treatment-resistant depression.
Progress in neuro-psychopharmacology & biological psychiatry December 20, 2022 John Cook, Angelos Halaris
Esketamine, approved by the FDA in early 2019 for treatment resistant depression, works by blocking NMDA receptors and improving symptoms rapidly through glutamatergic activation. Widespread use is limited by concerns about durability of response, especially during maintenance. Since esketamine must be taken with an oral antidepressant, choosing the right combination may improve outcomes. Because many patients with major depressive disorder and treatment resistant depression have dysfunction in dopaminergic pathways, adding a prodopaminergic agent like bupropion could enhance and prolong response. Anecdotal evidence and mechanistic rationale support this approach, and the oral combination of dextromethorphan and bupropion (AXS-05) has shown promise in clinical trials. This paper argues that dopaminergic enhancement may boost esketamine's efficacy and durability, encouraging further research.