Managing Esketamine Treatment Frequency Toward Successful Outcomes: Analysis of Phase 3 Data

Int J Neuropsychopharmacol. 2020 Jul 29;23(7):426-433. doi: 10.1093/ijnp/pyaa027.

Abstract

Background: Esketamine nasal spray was recently approved for treatment-resistant depression. The current analysis evaluated the impact of symptom-based treatment frequency changes during esketamine treatment on clinical outcomes.

Methods: This is a post-hoc analysis of an open-label, long-term (up to 1 year) study of esketamine in patients with treatment-resistant depression (SUSTAIN 2). During a 4-week induction phase, 778 patients self-administered esketamine twice weekly plus a new oral antidepressant daily. In responders (≥50% reduction in Montgomery-Åsberg Depression Rating Scale total score from baseline), esketamine treatment frequency was thereafter decreased during an optimization/maintenance phase to weekly for 4 weeks and then adjusted to the lowest frequency (weekly or every other week) that maintained remission (Montgomery-Åsberg Depression Rating Scale ≤ 12) based on a study-defined algorithm. The relationship between treatment frequency and symptom response, based on clinically meaningful change in Clinical Global Impression-Severity score, was subsequently evaluated 4 weeks after treatment frequency adjustments in the optimization/maintenance phase.

Results: Among 580 responders treated with weekly esketamine for the first 4 weeks in the optimization/maintenance phase (per protocol), 26% continued to improve, 50% maintained clinical benefit, and 24% worsened. Thereafter, when treatment frequency could be reduced from weekly to every other week, 19% further improved, 49% maintained benefit, and 32% worsened. For patients no longer in remission after treatment frequency reduction, an increase (every other week to weekly) resulted in 47% improved, 43% remained unchanged, and 10% worsened.

Conclusions: These findings support individualization of esketamine nasal spray treatment frequency to optimize treatment response in real-world clinical practice.

Trial registration: ClinicalTrials.gov identifier: NCT02497287.

Keywords: Esketamine; dosing; s-ketamine; treatment-resistant depression.

Publication types

  • Research Support, Non-U.S. Gov't

Associated data

  • ClinicalTrials.gov/NCT02497287