Skip to content
DraconiticResearch
Search Sources API
181,716 studies31 sourcesUpdated 45 min ago
Peer-reviewedCC BY 4.0Depression and Anxiety

Oral Esketamine Maintenance Treatment for Treatment‐Resistant Depression: Clinical Outcomes During an Off‐Label Treatment Program

  • Sanne Y. Smith-Apeldoorn1
  • Jolien K. E. Veraart1,2
  • Jan Spijker3,4
  • Annemarie Van Der Meij3
  • Jeanine Kamphuis1
  • Robert A. Schoevers1
4 affiliations
  1. 1Department of Psychiatry University of Groningen University Medical Center Groningen Groningen Netherlands umcg.nl
  2. 2Department of Psychiatry PsyQ Haaglanden Parnassia Psychiatric Institute The Hague Netherlands
  3. 3Depression Expertise Center Pro Persona Mental Health Care Nijmegen Netherlands
  4. 4Behavioral Science Institute Radboud University Nijmegen Netherlands ru.nl
Read full textPDFDOICite

Abstract

Ketamine and esketamine maintenance treatment show promise in maintaining initial antidepressant effects, yet further research is needed to optimize long‐term outcomes. This observational study aimed to assess long‐term depression symptom severity, safety, and tolerability in a cohort of patients receiving at‐home oral esketamine maintenance treatment. Between June 2017 and March 2024, 221 patients with severe treatment‐resistant unipolar depression were enrolled directly or trial‐transferred into an off‐label induction treatment program. After 6 weeks of individually titrated oral esketamine (twice a week, max 3.0 mg/kg) administered in the clinic, 93 patients continued to maintenance treatment at home (max 3.0 mg/kg twice a week). Our primary outcome was change in depression symptom severity during maintenance treatment, measured by the 17‐item Hamilton Depression Rating Scale (HDRS17). Mean exposure to esketamine in the maintenance phase was 20.8 months. We found no difference between the HDRS17 total score at the maintenance baseline and last‐observation‐carried‐forward (mean difference = 0.825, 95% CI = −0.759 to 2.410, p = 0.302). Of the 26 initial responders (≥50% decrease in HDRS17 at the end of induction treatment), 23.1% met sustained response criteria throughout maintenance treatment. Of the 40 patients meeting minimal clinically important difference (MCID) criteria (≥27.1% decrease in HDRS17 at the end of induction treatment), 60.0% met sustained MCID criteria throughout maintenance treatment. Eleven patients (11.8%) successfully tapered off esketamine maintenance treatment. Twelve patients (12.9%) discontinued maintenance treatment (partly) due to adverse events. These findings suggest that oral esketamine maintenance home treatment may be associated with sustained symptom stability in patients with severe treatment‐resistant depression (TRD), although causal inferences cannot be drawn from this observational study. Although some potential long‐term side effects require monitoring and further examination, overall, treatment was safe and well‐tolerated.

Related

  1. Esketamine for Treatment-Resistant Depression
    Ioana Cristea, Martin Plöderl, Florian Naudet
    JAMA PsychiatryPeer-reviewedCC BY-NC 4.0Full textGeneral biologyPsychiatry & mental healthHAL
  2. Baseline Response Criterion and Changes in Emotional Bias as Markers of Esketamine Response in Treatment-Resistant Depression
    C. Muh, P. Favre, I. K. Lutkenherm +3
    medRxivPreprintCC BYFull textPsychiatry & mental healthmedRxiv
  3. Quality of Life in Patients with Treatment-Resistant Depression Treated with Intranasal Esketamine as Add-On Therapy to an SSRI-A Prospective, Comparative Study in Real-World Clinical Practice.
    Daniel Szawarnoga, Joanna Fojcik, Michał Górski +1
    Pharmaceuticals (Basel, Switzerland)Peer-reviewedCC BYFull textPharmacology & toxicologyEurope PMC
  4. Real-world clinical outcomes under intravenous and subcutaneous esketamine protocols for treatment-resistant depression: a multicenter, retrospective study
    Gilberto Sousa Alves, Humberto M. M Dos Santos, Samira D. Damasceno +7
    Frontiers in PsychiatryPeer-reviewedCC BY 4.0Full textPharmacology & toxicologyCrossrefEurope PMCPMC
  5. Single Intranasal Administration of the Psychedelic Mebufotenin for Treatment-Resistant Depression
    David Feifel, Mathieu Seynaeve, Wiesław Jerzy Cubała +12
    JAMAPeer-reviewedLicence not statedFull text1 citedPsychiatry & mental healthPMC

Cite

BibTeXRIS
BibTeX
@article{smithapeldoorn2026oral,
  title = {{Oral Esketamine Maintenance Treatment for Treatment‐Resistant Depression: Clinical Outcomes During an Off‐Label Treatment Program}},
  author = {Sanne Y. Smith-Apeldoorn and Jolien K. E. Veraart and Jan Spijker and Annemarie Van Der Meij and Jeanine Kamphuis and Robert A. Schoevers},
  journal = {Depression and Anxiety},
  year = {2026},
  month = oct,
  doi = {10.1155/da/8320239},
  url = {https://doi.org/10.1155/da/8320239},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Oral Esketamine Maintenance Treatment for Treatment‐Resistant Depression: Clinical Outcomes During an Off‐Label Treatment Program
AU  - Sanne Y. Smith-Apeldoorn
AU  - Jolien K. E. Veraart
AU  - Jan Spijker
AU  - Annemarie Van Der Meij
AU  - Jeanine Kamphuis
AU  - Robert A. Schoevers
PY  - 2026
DA  - 2026/10/29
JO  - Depression and Anxiety
DO  - 10.1155/da/8320239
UR  - https://doi.org/10.1155/da/8320239
AB  - Ketamine and esketamine maintenance treatment show promise in maintaining initial antidepressant effects, yet further research is needed to optimize long‐term outcomes. This observational study aimed to assess long‐term depression symptom severity, safety, and tolerability in a cohort of patients receiving at‐home oral esketamine maintenance treatment. Between June 2017 and March 2024, 221 patients with severe treatment‐resistant unipolar depression were enrolled directly or trial‐transferred into an off‐label induction treatment program. After 6 weeks of individually titrated oral esketamine (twice a week, max 3.0 mg/kg) administered in the clinic, 93 patients continued to maintenance treatment at home (max 3.0 mg/kg twice a week). Our primary outcome was change in depression symptom severity during maintenance treatment, measured by the 17‐item Hamilton Depression Rating Scale (HDRS17). Mean exposure to esketamine in the maintenance phase was 20.8 months. We found no difference between the HDRS17 total score at the maintenance baseline and last‐observation‐carried‐forward (mean difference = 0.825, 95% CI = −0.759 to 2.410, p = 0.302). Of the 26 initial responders (≥50% decrease in HDRS17 at the end of induction treatment), 23.1% met sustained response criteria throughout maintenance treatment. Of the 40 patients meeting minimal clinically important difference (MCID) criteria (≥27.1% decrease in HDRS17 at the end of induction treatment), 60.0% met sustained MCID criteria throughout maintenance treatment. Eleven patients (11.8%) successfully tapered off esketamine maintenance treatment. Twelve patients (12.9%) discontinued maintenance treatment (partly) due to adverse events. These findings suggest that oral esketamine maintenance home treatment may be associated with sustained symptom stability in patients with severe treatment‐resistant depression (TRD), although causal inferences cannot be drawn from this observational study. Although some potential long‐term side effects require monitoring and further examination, overall, treatment was safe and well‐tolerated.
SN  - 1091-4269
SN  - 1520-6394
ER  -