J Psychopharmacol

Oral esketamine shows promise for severe depression

May 1, 2025

Study details: This study evaluated the effectiveness, safety, and tolerability of oral esketamine in 185 adults with severe treatment-resistant depression (TRD) over a six-week open-label treatment program. Participants had previously undergone an average of 8.1 antidepressant trials and 63% had received electroconvulsive therapy without benefit. Esketamine was administered twice-weekly with doses ranging from 0.5 to 3 mg/kg, titrated individually.

Results: A significant reduction in depressive symptoms was found, with the Hamilton Depression Rating Scale (HDRS17) scores decreasing from 21.2 to 15.8 (p < 0.001). The rates for minimal clinically important difference, response, and remission were 47.1%, 26.8%, and 15.6%, respectively. Side effects were common but generally well tolerated, with a drop-out rate of 7.6%. No significant adverse effects on urinary tract or cognition were observed.

Clinical impact: Oral esketamine demonstrated effectiveness in reducing depressive symptoms in patients with severe TRD, with safety and tolerability comparable to other administration routes. The continuation of treatment in 45.9% of participants suggests potential for maintaining positive effects, suggesting oral esketamine's potential as a patient-friendly treatment option for TRD.

Source:

Veraart JK, et al. (2025, April 25). J Psychopharmacol. Oral esketamine for patients with severe treatment-resistant depression: Effectiveness, safety, and tolerability of a six-week open-label treatment program. https://pubmed.ncbi.nlm.nih.gov/40285334/