Esketamine Treatment Trajectory of Patients with Treatment-Resistant Depression in the Mid and Long-Term Run: Data from REAL-ESK Study Group

Curr Neuropharmacol. 2025;23(5):e1570159X337670. doi: 10.2174/011570159X337670241029062524.

Abstract

Introduction/objective: Data on long-term treatment with Esketamine Nasal Spray (ESKNS) in real-world patients with treatment resistant depression (TRD) is scarce. The primary aim of the study is to evaluate the effectiveness and tolerability of ESK-NS treatment at 6 and 12-month follow-ups.

Methods: This is part of an observational, retrospective, multicentric Italian study (REAL-ESK study). Subjects for the present study underwent psychiatric assessments after 6 and 12 months from the start of ESK-NS treatment. Repeated measures analysis of variance (ANOVA) was used to assess changes in continuous variables, such as scores on psychometric scales from baseline to follow-up time points.

Results: Of 63 patients who maintained ESK-NS treatment for at least 6 months, 48 were responders or remitters (76.2%). Among 15 non-responders at 6 months, 4 significantly improved at 12-month follow-up. At least one side effect was reported by 71.8% of subjects with a 6-month follow-up assessment. An overall reduction of side effects was noticed as treatment progressed (42% of patients who continued the treatment reported side effects at 12 months). The most common side effects were sedation (31.7%) and dissociation (28.6%) during ESK-NS sessions. Only 2 patients discontinued ESK-NS for tolerability reasons.

Conclusion: The results support the effectiveness and safety of esketamine in the mid and long-term treatment of TRD patients. The late clinical response of a subgroup of patients represents a novel finding. Data needs to be confirmed in larger samples and longer observation periods.

Keywords: Major depressive disorder; antidepressants; esketamine; maintenance treatment; treatment outcome.; treatment-resistant depression.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Administration, Intranasal
  • Adult
  • Aged
  • Antidepressive Agents / therapeutic use
  • Depressive Disorder, Treatment-Resistant* / drug therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Italy
  • Ketamine* / administration & dosage
  • Ketamine* / therapeutic use
  • Male
  • Middle Aged
  • Nasal Sprays
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Ketamine
  • Esketamine
  • Antidepressive Agents
  • Nasal Sprays