Oral esketamine for patients with severe treatment-resistant depression: Effectiveness, safety, and tolerability of a six-week open-label treatment program.
Jolien Ke Veraart, Sanne Y Smith-Apeldoorn, Annemarie van der Meij, Jan Spijker, Robert A Schoevers, Jeanine Kamphuis
Journal of psychopharmacology (Oxford, England) April 25, 2025 DOI: 10.1177/02698811251332831 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Naturalistic study Open-label Peer reviewed |
|---|---|
| Sample size | 185 |
| Population | Adults with severe treatment-resistant depression |
| Intervention | Oral esketamine |
| Dose | 0.5 to 3 mg/kg |
| Duration | 6-week intervention |
| Topics | Depression Esketamine Ketamine |
| Keywords | Oral esketamine Real-world effectiveness Mental health treatment Clinical research |
| Citations | 6 |
| Key points | Oral esketamine treatment improved depressive symptom severity in highly treatment-resistant patients, with outcomes comparable to other routes of ketamine administration. |
Abstract
Oral esketamine for patients with treatment-resistant depression (TRD) could offer certain advantages over other routes, such as intravenous or intranasal, but it has not been systematically studied in a real-world setting. Here we present results from a relatively large naturalistic study to evaluate the effectiveness, tolerability, and safety of oral esketamine in patients with TRD. One hundred eighty-five adults with severe TRD (average of 8.1 antidepressant trials plus electroconvulsive therapy in 63% without beneficial outcome) received oral esketamine treatment twice-weekly for 6 weeks with individually titrated doses ranging from 0.5 to 3 mg/kg. Outcome measures included change from baseline to week 6 on the Hamilton Depression Rating Scale (HDRS17), Minimal Clinically Important Difference (MCID), response, remission, self-reported symptom improvement, functioning, and side effects. Oral esketamine treatment improved depressive symptom severity on the HDRS17 from 21.2 to 15.8 (p < 0.001). MCID, response, and remission rates were 47.1%, 26.8% and 15.6% respectively. In 45.9% of participants, treatment was continued after 6 weeks to maintain initial positive effects. Side effects were reported frequently but were overall well tolerated. The drop-out rate was 7.6%. We found no significant adverse effects associated with urinary tract or cognition. Repeated treatment with oral esketamine is effective in improving depressive symptom severity in highly treatment-resistant depressive patients. It is safe, well tolerated, and patient-friendly. Considering the level of treatment resistance, outcomes were in the range of studies investigating other routes of (es)ketamine administration.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.