J Clin Psychiatry

IV vs. intranasal ketamine in treatment-resistant depression: Which is more effective?

October 3, 2025

Study details: In this retrospective chart review conducted at McLean Hospital, researchers analyzed outcomes from 153 adults with treatment-resistant depression (TRD). Patients had failed ≥2 prior antidepressant trials and had baseline 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR₁₆) scores ≥16. The cohort included 111 patients treated with IV ketamine and 42 with intranasal (IN) esketamine, each administered twice weekly over 4 to 5 weeks (eight sessions total).

Results: Both treatments significantly reduced depression severity. However, IV ketamine led to faster and more pronounced improvements: a 49.22% reduction in QIDS-SR₁₆ scores by the eighth session, compared with 39.55% with IN esketamine. IV ketamine showed significant symptom relief after the first dose, while esketamine’s effects emerged after the second.

Clinical impact: IV ketamine may offer more rapid and robust symptom relief for TRD, though both modalities are effective. Treatment choice should consider clinical context, patient preference, access, and safety. Further randomized trials are needed to confirm these results and guide individualized care.

Source:

Meisner R, et al. (2025, September 22). J Clin Psychiatry. Comparative Effects of Repeated Ketamine Infusion Versus Intranasal Esketamine in Patients With Treatment-Resistant Depression: A Retrospective Chart Review. https://pubmed.ncbi.nlm.nih.gov/41004170/