Vol. 7, Issue 1, Part D (2025)

Background: Treatment-resistant depression (TRD) remains a topic that warrants investigation in both preclinical and clinical settings. Emerging hypotheses involving the glutamatergic and GAB Aergic pathways have opened up a gateway to new treatment plans aside from traditional antidepressants. Ketamine’s function as a prototypical N-methyl-d-aspartate (NMDA) receptor antagonist that exerts rapid antidepressant and antisuicidal effects overlaps with the functions of Auvelity. This overlapping mechanism demonstrates a compounding efficacy comparable to other emerging agents. However, their inherent limitations restrict widespread use, leading to the proposal of an adjusted approach.
Case presentation: A 34-year-old woman showed partial response to multiple antidepressants (desvenlafaxine, bupropion) while experiencing persistent depressive symptoms. She then received weekly ketamine infusions for two years with adjusted previous oral medications. Then she started to take Auvelity every day. Her depressive symptoms markedly improved, allowing her to manage daily life and childcare.
Conclusion: This case report underscores a novel therapeutic approach in TRD by introducing a sequential strategy of ketamine induction followed by Auvelity maintenance. While ketamine provides rapid antidepressant and antisuicidal effects, Auvelity may extend these benefits by sustaining glutamatergic modulation. To our knowledge, this appears to be the first report to apply such a strategy, offering important clinical insight and opening new avenues for developing durable treatment options in TRD.